Supplement 2/2010 - · PDF fileEugen Boia, Timisoara, Romania ... Gabriela Doros, Timisoara, Romania George-Lucian Moldovan, Boston, USA Gertrude-Emilia Costin, ... Supplement 2/2010

Supplement 2/2010

� RomanianJournalofRareDiseases|Supplement 2/2010

EditorinChiefMaria PuiuDepartment of Medical GeneticsUniversity of Medicine and Pharmacy„Victor Babes”Timisoara, RomaniaTel/fax: +40 256 220479E-mail: [email protected]

AssistantEditorsCristina RusuCristina SkrypnykVlad Gorduza

SecretaryVlad L. David

EditorialBoardDorica DanAdela Chirita-Emandi Amelia DobrescuMihai GafencuSimona FarcasDiter AtasieRadu PoppCristina PopaCorina Duncescu

HonoraryMembersSégolène Aymé,FranceGheorghe Benga,RomâniaAnna & Giuseppe Baschirotto,ItalyFRAMBU,Norway

Romanian Journal of Rare DiseasesISSN2068–5882

[email protected]:„VictorBabes”PrintingHouseAddress:P-taEftimieMurgu2,300041Timisoara,RomaniaTel./fax:0256/[email protected]

Scientific boardAdrian C. Nicolescu, Kingston, Canada, Adrian Lupescu, Tuebingen, GermanyAlex Almasan, Cleveland, Ohio, USAAlexander Rodewald, Germany Alice C. Ceacareanu, New York, USAAurelia Szekely, Zalau, RomaniaBogdan Iorga, Köln, GermanyCalin Popoiu, Timisoara, RomaniaCassian Sitaru, Freiburg, GermanyClaudia Cosmineanu-Halaby, New York, USACristina Rusu, Iasi, RomaniaCristina Skrypnyk, Oradea, RomaniaCurocichin Ghenadie, Chisinau, MoldaviaDanalache Bogdan Alexandru, Montreal, CanadaDorin Bogdan Borza, Nashville, USADumitru Andrei Iacobas, New York, USADumitru Moldovan, Tg. Mures, RomaniaEmilia Severin, Bucuresti, RomaniaEugen Boia, Timisoara, RomaniaGabriela Anton, Bucuresti, RomaniaGabriela Doros, Timisoara, RomaniaGeorge-Lucian Moldovan, Boston, USAGertrude-Emilia Costin, Maryland, USAIgor Cemortan, Chisinau, MoldaviaIoan Simedrea, Timisoara, RomaniaIonel Sandovici, Cambridge, UKKatalin Csep, Tg. Mures, RomaniaLeonard Girnita, Stockholm, SuediaMarcel Ionita, Birmingham, USAMargit Serban, Timisoara, RomaniaMaria Puiu, Timisoara, RomaniaMarius Bembea, Oradea, RomaniaMihai D. Niculescu, Chapel Hill, USAMinodora Dobreanu, Tg. Mures, RomaniaMircea Covic, Iasi, RomaniaMircea Ivan, Bloomington, USANatalia Cucu, Bucuresti, RomaniaPeter Manu, New York, USASanda Marchian, Sibiu, RomaniaSergiu P. Pasca California, USASorin Ursoniu, Timisoara, RomaniaTamás Jánossy, Szeged, HungaryTudor Oprea, New Mexico, USAValerica Belengeanu, Timisoara, RomaniaVictor I. Pop, Cluj-Napoca, RomaniaVlad Gorduza, Iasi, Romania

RomanianJournalofRareDiseases|Supplement 2/2010 �

ABOUTTheRomanian Journal of Rare Diseases©isaninterna-tionaljournaladdressingrarediseasesandorphandrugsfromtheperspectivesofbasicandclinicalgenetics,moleculargenetics,cytogenetics,epigenetics,populationgenetics,biotechnology,neurogenetics,cardiogenetics,oncogenetics, pharmacogenetics and related fields, by publishingoriginalworks,reviewarticles,clinicalreportsandothercontributionsfromallareascoveredbyTheRomanian Journal of Rare Diseases©.Thispublicationis the international official journal of the National Com-mitteeforRareDiseases,foundedandstartedaspartoftheprojectoftheRomanianPraderWilliAssociation,„TheNorwegian-RomanianPartnership(NoRo)forprog-ressinRareDiseases”fundedbytheNorwegianGovern-mentgrantedbytheNorwegianCooperationProgramforgrowthandsustainabledevelopmentinRomania.TheRomanianPraderWilliAssociationandthe„VictorBabes”PublishingHouse,E.MurguSquare2,300041,Timisoara,tel./fax.0256220479,publishthejournalquarterly

PURPOSE&AREAOFINTERESTForthejournalareofinterestarticlesfrombasicandclinicalresearch.Thejournalpublishesoriginalarticles,shortreports,specialcommunications,providedthattheyarebasedonadequateexperimentalevidence,clinicalstudies,casereports,imagesinrarediseases,letterstotheeditor,bookreviews,reportsofcongressesandotherarticlesthatwillbebroughttoEditorialBoard’satten-tionbasedonthepublic’sforthejournal.Editorialsarepublishedbyinvitationbutwelookforwardtobeofferedsuchmaterialfromresearcherswithexperienceandre-sultsinthestudyofrarediseases.Requirementsforpub-licationintheRomanianJournalofRareDiseasesareinaccordancewiththerequirementsof„UniformRequire-mentsforManuscriptsSubmittedtoBiomedicalJournals”5thEdition.JAMA1997,277:927-934.

LEGALDISCLAIMERTheentirecontentsoftheRomanian Journal of Rare Diseases©areprotectedunderinternationalcopyrights©.Theauthorsbaretheentireresponsibilitiesforthecon-tentofthearticle.



INVITATIONROMANIAN PRADER WILLI ASSOCIATION

in partnership with

INTERNATIONAL PRADER WILLI ORGANISATION NORWEGIAN PRADER WILLI ASSOCIATION

FRAMBU RARE DISEASE CENTRE – NORWAYRomanian Society of Medical Genetics

and

MEDICAL GENETICS Department of the University of Medicine and Pharmacy V. BABEŞ, TIMIŞOARA

organise

The Second Eastern-European Prader Willi Syndrome Conference

October 29- 30, 2010Zalău

Coordinators Dorica Dan, Prof. Dr. Puiu Maria and Dr. Susanne Bliechfeldt

The conference will be attended by national and international specialists, highly experiencedin the field of rare disease management, in general, and Prader Willi Syndrome, in particular. RepresentativesoftheRomanianHealthMinistry,EmbassyofNorwayinRomaniaandlocalauthoritieswillalsoattend.

Wearethereforeinviting you to this event, which will be officially opened at Grand Hotel Severus onFriday,October29th2010,at9.00.

Thank you for your support and we are looking forward to seeing you,

Dorica DanAPWR President


Friday, 29 October 201008.00–09.00 Registration of participants

09.00-10.00

Official opening of congressWelcome speech and introduction (APWR, IPWSO, EURORDIS, Health Ministry, Innovation Norway, partners and local authorities) Chair – Dorica Dan

10.00-11.00NEWS IN PWSModerators:Christel Norissier,France,EURORDIS–EUCERDDorica Dan,APWR

10.00–10.20 CommunicationThe 7th Scientific conference of the International PWS Organisation Antony Holland,Cambridge, UK

10.20-10.50 Communication

News about Prader-Willi Syndrome. Clinical research presented at the IPWSO Conference in Taiwan 2010Susanne Blichfeldt. MD. Paediatric department. Glostrup University Hospital. 2600 Glostrup. Denmark

10.50-11.10 Communication Results of the Caregiver’s Conference in TapeiHubert Soyer, Germania

11.10–11.15 Discussions Q&A

11.15-11.45 Coffee break

11.45-12.00 CommunicationThe Romanian Prader Willi Association – Prader Willi Syndrome a model for approaching rare diseases in RomaniaDorica Dan–president RPWA

12.00-12.15 CommunicationPresentation of the Project „Norwegian Romanian (NoRo) Partnership for Progress in Rare Diseases”Lázár Zsuzsa,RPWA, Zalau

12.15-12.55 ReportGeneral health in Prader-Willi syndromeSusanne BlichfeldtMD. Department of Paediatrics. Glostrup University Hospital. 2600 Glostrup, Denmark

12.55-13.00 Discussions Q&A

13.00-14.00 Lunch break

The Second Eastern-European Prader Willi Syndrome Conference

P R O G R A M


14.00–15.30 Specific issues in PWS(part I)Moderators:Susanne Blichfeldt (Denmark),MariaPuiu(Timisoara,Romania)


Romania: Research in PWS – Together with and for PatientsMaria Puiu1, Mihai Gafencu1, Dorica Dan2, Margit Serban1,

1 University of Medicine and Pharmacy, Timisoara, Romania,2 APWR, Zalau


Epigenetic mechanisms underlying the imprinting defects: implications for the establishment of diagnostic testing schemes for Prader Willi syndrome in Romanian population.NataliaCucu1,GabrielaAnton2,MariaPuiu3,CosminArsene1,AncaBotezatu2,CorinBadiu4,VasilicaPlaiasu5,DanielaNedelcu5,RaduStefanescu5

1 University of Bucharest, Faculty of Biology, Dept of Genetics, Epigenetics Laboratory2 „Stefan Nicolau” Institute of Virology, Dept of Molecular Biology, Bucharest3 Medical and Pharmaceutical University Timisoara4 “N Parhon” Institute of Endocrinology, Bucharest5 Genexplore, Bucharest


The cytogenetic investigation before and after birth, GorduzaE.V.1

1 University of Medicine and Pharmacy „Gr. T. Popa” Iaşi, Department of Medical Genetics

14.45-15.00 CommunicationEndocrine obesity in Prader Willi syndromeCorin Badiu,GabiMadarasNational Institute of Endocrinology, Bucharest, Romania

15.00-15.15 CommunicationNeurological aspects in PWS, VioletaStanUniversity of Medicine and Pharmacy “V Babes”, Timisoara

15.15-15.30 Discussions


16.00–17.30 Specific issues in PWS(part II)Moderators:Arnesen Ragnhild (PWANorway),VladGorduza(Iasi,Romania).

16.00-16.15 Communication Obesity and diabetes in Prader Willi Syndrome (PWS)AureliaSzekely,ZsuzsaLázár,Zalau


Prader-Willi Syndrome rare facts – cardiac, renal and poisoning complicationsGafencuMihai,GabrielaDoros,MariaPuiuUniversityofMedicineandPharmacy“VBabes”,Timisoara


Reduced deep sleep efficiency without excessive daytime somnolence in advanced and severe concomitant obstructive sleep apnea - hypopnea and Prader Willi syndromeStefanFrent,StefanMihaicuta,UMFV.BabesTimisoara


16.45-17.00 CommunicationRecommendations for the Diagnosis and Management of Prader-Willi Syndrome. Effects of growth hormone therapy in children, DanaDavid,RalucaDumache,UMFV.BabesTimisoara


Orthopedic and Surgical Features in Patients withPrader Willi Syndrome PopoiuMC1,DavidVL2,BoiaES1,MariaPuiu11University of Medicine and Pharmacy “Victor Babes” Timisoara2Emergency Children’s Hospital “Louis Turcanu” Timisoara


17.30-18.00 IPWSO – achievements and perspectives; GiorgioFornasier–CEOIPWSO;

19.00-20.00 Dinner

Saturday, 30 Octombrie, 2010

09.00–11.00 Interdisciplinary approaches in PWS.Moderators:Giorgio Fornasier, Antony Holland, Kaja Giltvedt

09.00-09.30 ReportThe impact of the National plans on the life of people living with Prader-Willi syndrome in FranceChristelNourisier,Franta,BoDEURORDIS,EUCERDmember

09.30-10.00 Report Psychiatric aspects in PWS, AntonyHolland,Cambridge,GreatBritain

10.00-10.30 Report

Ethical management of patients with Prader-Willi syndrome across life spanVioletaOliviaStan,UniversityofMedicineandPharmacy“VBabes”,Timisoara

10.30-10.45 Communication Particular forms of Prader Willi syndrome – clinical and genetic study, C.Rusu,C.Vulpoi,E.Braha,M.Volosciuc,I.Ivanov,C.Gorduza,V.Gorduza,M.Puiu,D.Dan,UMFIasi

10.45-11.00 Communication Nutrition management in Prader Willi syndrome, AdelaChirita,UniversityofMedicineandPharmacy“VictorBabes”Timisoara

11.00-11.30 Coffee break. Poster session.

11.30-12.15 Communication Prader-Willi syndrome and physiotherapyGiltvedt, Kaja, Lisen Mohr,FrambuResourceCentreforRareDisorders,OsloNorway


12.30–14.00Changes throughout life.Moderators:Anna and Giuseppe Baschirotto,BIRDItaliaIoana Rotaru –ACASAFoundation,Romania

12.30-12.45 CommunicationTransition to adulthood: What is a good life for persons with PWS? RagnhildArnesen,NorwayPraderWilliAssocoiation

12.45-13.00 CommunicationUnderstanding and managing educational issues in Prader-Willi syndrome, Amalia Raluca Sabău, TheRomanianPraderWillliAssociation


13.00-13.15 CommunicationBehavioral interventions in PWSSimonaDumitriu,UniversityofMedicineandPharmacy“VBabes”,Timisoara

13.15-13.30 Communication Art therapy activities for PWS children and teenagersMihaiela Fazecas, Emese Darko, APWR


Nursing aspects for PWS patients Livia Berinde, Claudia GoronRehabilitation, Treatment and Care Center “ACASA” Zalau, Romania


14.00-15.00 Lunch

15.00-17.00Best practice examples in approaching PWS patients Moderators:Lisen Julie Mohr,Frambu,NorvegiaConf. Dr. Crisina Rusu,UMFIasi

15.00-15.30 Communication Personal experience in PWSGiorgio Fornasier, Italy


Disease specific rehabilitation in Prader-Willi syndrome, Emanuele Grolla1, Gilberto Andrighetto1, Pietro Parmigiani1, Uros Hladnik1, Gabriela Ferrari1, Roberta Bernardelle1, Martina Dal Lago1, Anna Albarello1, Giuseppe Baschirotto1, Giuseppe Filippi2, Roberto Lovato3, Diego Dolcetta1

1 „M. Baschirotto” Institute for Rare Diseases - B.I.R.D., Centro Diagnostico Riabilitativo per la Diagnosi Terapia e Cura delle Malattie Rare, Costozza di Longare-Vicenza, Italy2“Camillo de Lellis” Hospital, Department of Rehabilitation “Alto Vicentino”, ULSS4-Schio, Italy; 3“Villa Berica” Hospital, Vicenza, Italy

15.45-16.00 Communication„NORO“- ONE STEP TOWARDS A SUCCESSFULL REHABILITATION Ioana Rotaru,Rehabilitation, Treatment and Care Center “ACASA” Zalau, Romania


The project “The National Center for employment opportunities for people with multiple sclerosis and other neurological rare diseases - Ability Access”, ClaudiaTorje–managerdeproiect,RomanianMultipleSclerosisSociety

16.15-16.30 CommunicationRare Disease CommunitiesRobert Pleticha, Online Patient Communities Coordinator,Eurordis

16.30-16.45

Volunteers for rare diseases- 3 years, IuliaJurca-Simina,FlorinJurca-Simina,IonelaMoaca,PopNorbert,BerciStefan,IuliaPopa,MihaiGafencu,MariaPuiu-volunteers in “Save the Children” organization, Timis office

16.45-17.00 Discutii Norway(FRAMBU),Italy(BIRD),Romania,Denmark,France,Germany


17.30-18.00 Conclusions. Closure of conference.

10 RomanianJournalofRareDiseases|Supplement 2/2010

PoSTErECHANGING PHENOTYPES IN PRADER WILLI SYNDROMEAdelaChiritaEmnadiUniversity of Medicine and Pharmacy “V Babes”, Timisoara

THE GROWING PATTERN IN A PATIENT WITH PRADER-WILLI SYNDROME AFTER GH THERAPYGorduzaN.C.1,BrahaE.E.2,GorduzaE.V.1

1 „St. Spiridon” Hospital Iaşi, Clinic of Endocrinology, 2 Uiversity of Medicine and Pharmacy „Gr. T. Popa” Iaşi, Department of Medical Geneticse-mail: [email protected]

NEWBORN WITH HYPOTONIA AND DISTURBANCES OF ENDOCRINE-METABOLIC FUNCTIONS DIAGNOSES WITH PRADER-WILLY SYNDROMEMonica Stoian¹, Maria Puiu¹, Simona Farcas¹, Nicoleta Andreescu¹, Marioara Boia², ValericaBelengeanu¹¹ Department of Medical Genetics, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania² Department of Neonatology, “Louis Turcanu” Children Hospital, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romaniae-mail: [email protected]

PERSPECTIVE DATA FOR CEPHALOMETRIC ANALYSIS AND ORODENTAL PATTERN FOR ROMANIAN PRADER-WILLI SYNDROME PATIENTSDragosBelengeanu¹,AngelaPodariu²,MonicaStoian³,MariaPuiu³,DoricaDan4

¹ College of Dental Technique, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania² Department of Medical Dental Prevention and Oral Health, University of Medicine and Pharmacy „Victor Babes”, Timisoara, Romania³ Department of Medical Genetics, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania4 Romanian Prader-Willi Syndrome Associatione-mail: [email protected]

DIGESTIVE DISORDERS IN PRADER WILLI SYNDROMEMariaPop,MariaPuiu,University of Medicine and Pharmacy “V. Babes”, Timisoara

EMOTIONAL AND BEHAVIOURAL PROBLEMS IN PRADER WILLI SYNDROMECatanaAndreea,DroncaEleonora,SerbanSimona,MicleaDiana,PopIonut,FeliciaPetrisor,PopI.VictorUniversity of Medicine and Pharmacy, Cluj-Napoca, Romania

THE IMPACT OF THE DIAGNOSIS AND DISABILITY ON THE FAMILY AND PERSON WITH PRADER-WILLI SYNDROMEDroncaEleonora,CatanaAndreea,SerbanSimona,MicleaDiana,PopIonut,PopIVictorUniversity of Medicine and Pharmacy, Cluj-Napoca, Romania

HEALTH ISSUES AND CONCERNS IN PRADER WILLI SYNDROMESerbanSimona,CatanaAndreea,DroncaEleonora,MicleaDiana,PopIonut,PopIVictorUniversity of Medicine and Pharmacy, Cluj-Napoca, Romania

RomanianJournalofRareDiseases|Supplement 2/2010 11

A FEW WAYS TO MANAGE BEHAVIORAL DISTURBANCES IN PRADER WILLI SYNDROMEMarianaCojocaruPhD Student, “Carol Davila” Univ Med Pharm, Bucharest – Romania

C-FLIP REGULATION OF ENDOTHELIAL CELLS APOPTOSIS IN THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) – LIKE CONDITIONSJeffreyLaurence1,andRaduStefanescu2,3

1 Department of Medicine, Division of Hematology-Oncology, Weill Medical College–Cornell University, New York, NY; 2 Titu Maiorescu School of Medicine, Bucharest, Romania; and 3 GeneXplore, Romania

LOBAR HOLOPROSENCEPHALY-A RARE DISEASEMarioaraBoia1,E.S.Boia*,MariaPuiu**,DanaIacob*,AnikoManea*University of Medicine and Pharmacy ”Victor Babes”, Timisoara, RomaniaKeywords: holoprosencenphaly, echography, newborn

EFFECTIVE REHABILITATION TREATMENT IN A CASE WITH DOUBLE CHROMOSOMAL DELETIONDorinaSTOICANESCU1,MarianaCEVEI21University of Medicine and Pharmacy “Victor Babes”, Department of Medical Genetics, Timisoara, Romania2University of Oradea, Faculty of Medicine and Pharmacy, Medical Rehabilitation Clinical Hospital Felix Spa, Oradea, Romania

ORAL MANIFESTATIONS INCLUDING GINGIVAL FIBROMATOSIS IN RARE DISEASESTalpoş Ş, Puiu M, Talpoş C, Popa MUniversity of Medicine and Pharmacy “Victor Babeş” Timişoara, RomaniaFaculty of Dental MedicineDepartment of Oral and Maxillo-Facial SurgeryDepartment of Medical Genetics

CLINICA AND BIOLOGICAL CONFIRMATIONIN AN SUSPICION OF GLUT1 DEFICIENCY SYNDROMEDumitriuSimona,University of Medicine and Pharmacy “Victor Babeş” Timişoara, Romania

FROM A PARTICULAR PHENOTYPE TO A RARE GENETIC DISEASE – A PEDIATRIC APPROACHT.Marcovici1,2,I.Simedrea1,2,G.Brad2,L.Olariu1,2,M.Puiu1,2

1 „Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania2 „Louis Turcanu” Children’s Emergency Hospital, Timisoara, RomaniaEmail: [email protected]

GENETIC COUNSELORS AND PREDICTIVE MEDICINE: A NEEDED PROFESSION IN ROMANIAMariaPuiu1, Adela Chiriţă1,DoricaDan2

1 “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania2 Romanian Prader Willli Association

ASESSMENT OF MULTIPLE MALFORMATION IN NEWBORN. CASE REPORT.BeleiOana,GiurescuRamona,MicleIoana,PopElena,MarazanMonica,SimedreaIoan,PuiuMariaFirstPediatricClinic,UMFVictorBabesTimisoara

A RARE CASE OF HEPATOMEGALYMariaPop1,2,I.Plesea2,B.Farcasescu2,M.Serban1,2

1 “Victor Babes” University of Medicine and Pharmacy Timisoara 2 “Louis Turcanu” Emergency Children Hospital – IIIrd Pediatric Clinic

1� RomanianJournalofRareDiseases|Supplement 2/2010

A NEW CASE ��,XX MALE SYNDROMECristinaGug1,2

1 Genetics Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania 2 Cabinet Medical de Genetica ”Dr. Cristina Gug”, Timisoara, Romania

RARE CAUSE OF HEMOPHAGOCYTIC DISORDER - CHEDIAK-HIGASHI SYNDROME-CASE REPORTE.Boeriu1,2,M.Cucuruz1,2,M.Lelik1,2,G.Brad1,2,I.Ursache1,2,A.Botiz1,M.Puiu,M.Serban1,2

1 Children’s Emergency Hospital “Louis Turcanu, Timisoara 2 3rd Pediatric Clinics, Hemato-Oncology Department, University of Medicine and Pharmacy “V. Babes “Timisoara

PALLIATIVE MEDICINE IN RARE DISEASES - INTERFERENCE AND CHALLENGESE.Boeriu1,2,M.Cucuruz1,2,S.Arghirescu1,2,R.Costea1,G.Brad1,I.Ursache1,M.Serban1,2

1 Children’s Emergency Hospital “Louis Turcanu”, Timisoara 2 III Pediatric Clinic, Department of Hematology-Oncology University of Medicine and Pharmacy “Victor Babes” Timisoara

PRIMARY IMMUNODEFICIENCIES - CURRENT DIAGNOSIS AND MANAGEMENT MariaCucuruz1,EsteraBoeriu1, Mihaela Bătăneanţ1,GiorgianaBrad1,MariaPuiu2

1 III Pediatric Clinic, University of Medicine and Pharmacy “Victor Babes” Timisoara; 2 Discipline of Genetics University of Medicine and Pharmacy “Victor Babes” Timisoara

THE NEONATAL SCREENING FOR CONGENITAL HYPOTHYROIDISM IN TIMIS AREA – 10 YEARES OF EXPERIENCE OtiliaMarginean1,IoanSimedrea1,IoanaMicle1,MarilenaLesovici1,OlaruGabriela2,IlieConstantin3,MariaPuiu1,RoxanaGruescu1,ElenaJivet1,TiraMaria1,1. Clinical Children Hospital „ Louis Turcanu” Timisoara2. „Marin pPopescu ” Maternity of Timisoara3 Bega Maternity of Timisoara

RomanianJournalofRareDiseases|Supplement 2/2010 1�

Table of contents

REPORTS (FOLLOWING CONGRES PROGRAM)

1. Psychiatric aspects in PWS ..................................................................... 16

2. News about Prader-Willi Syndrome. Clinical research presented at the IPWSO conference in Taiwan 2010 ............................................................... 16Susanne Blichfeldt3. Results of the Caregiver’s Conference in Tapei ............................................ 17Hubert Soyer, Germania4. The Romanian Prader Willi Association – Prader Willi Syndrome a model for approaching rare diseases in Romania ........................................................... 17Dorica Dan – president RPWA5. Presentation of the Project „Norwegian Romanian (NoRo) Partnership for Progress in Rare Diseases” ......................................................................... 18Lázár Zsuzsa, RPWA, Zalau6. GENERAL HEALTH IN PRADER-WILLI SYNDROME ............................................ 19Susanne Blichfeldt MD7. Romania: research in rare diseases – totghether and for patients ..................... 19Maria Puiu, Mihai Gafencu, Natalia Cucu, Dorica Dan, Margit Serban8. Epigenetic mechanisms underlying the imprinting defects: implications for the establishment of diagnostic testing schemes for Prader Willi syndrome in Romanian population ............................................................... 20Natalia Cucu, Gabriela Anton, Maria Puiu, Cosmin Arsene, Anca Botezatu, Corin Badiu, Vasilica Plaiasu, Daniela Nedelcu, Radu Stefanescu 9. The cytogenetic investigation before and after birth .................................... 21Gorduza E.V.10. Endocrine obesity in Prader Willi Syndrome .............................................. 21Corin Badiu, Gabi Madaras11. Neurological aspects in PWS .................................................................. 22Violeta Stan, Emergency Children’s Hospital “Louis Turcanu” Timisoara 12. Obesity and diabetes in Prader Willi Syndrome (PWS) .................................. 22Aurelia Szekely, Zsuzsa Lázár13. Prader-Willi Syndrome rare facts cardiac, renal and poisoning complications ..... 22Gafencu Mihai, Gabriela Doros, Maria Puiu14. Reduced deep sleep efficiency without excessive daytime somnolence in advanced and severe concomitant obstructive sleep apnea - hypopnea and Prader Willi Syndrome .............................................................................. 23Stefan Frent, Stefan Mihaicuta15. Recommendations for the Diagnosis and Management of Prader-Willi Syndrome. Effects of growth hormone therapy in children ............................................... 23Dana Liana David, Raluca Dumache 16. Orthopedic and Surgical Features in Patients with Prader Willi Syndrome ........ 24Popoiu MC, David VL, Boia ES, Maria Puiu17. The impact of the National plans on the life of people living with Prader-Willi syndrome in France ................................................................. 25Christel Nourisier, Franta, BoD EURORDIS 18. Psichiatric aspects in PWS .....................................................................26Antony Holland, Cambridge, UK19. Ethical management of patients with Prader-Willi syndrome across life span ..... 26Violeta Olivia Stan 20. Particular forms of Prader Willi syndrome – clinical and genetic study ........... 28C. Rusu, C. Vulpoi, E. Braha, M. Volosciuc, I. Ivanov, C. Gorduza, V. Gorduza, M. Puiu, D. Dan


21. Nutrition management in Prader Willi syndrome ........................................ 28Adela Chirita22. PRADER-WILLI SYNDROME AND PHYSIOTHERAPY ......................................... 29Giltvedt, Kaja and Lisen Mohr23. TRANSITION TO ADULTHOOD: WHAT IS A GOOD LIFE FOR PERSONS WITH PWS? ...29Arnesen, R.O.24. Understanding and managing educational issues in Prader-Willi Syndrome ....... 30Amalia Raluca Sabău25. Behavioral interventions in PWS ............................................................ 30Simona Dumitriu26. Art Therapy Activities for Children and Adolescents with Prader Willi Syndrome ....................................................................................... 31Mihaiela Fazecas, Emese Darko27. Nursing aspects for PWS patients ........................................................... 31Livia Berinde, Claudia Goron28. Disease specific rehabilitation in Prader-Willi Syndrome .............................. 32Emanuele Grolla, Gilberto Andrighetto, Pietro Parmigiani, Uros Hladnik, Gabriela Ferrari, Roberta Bernardelle, Martina Dal Lago, Anna Albarello, Giuseppe Baschirotto, Giuseppe Filippi, Roberto Lovato, Diego Dolcetta29. „NORO”- ONE STEP TOWARDS A SUCCESSFULL REHABILITATION ...................... 32Ioana Rotaru 30. The National Center for employment opportunities for people with multiple sclerosis and other neurological rare diseases - Ability Access ........................... 33Claudia Torje31. Rare Disease Communities ................................................................... 33Robert Pleticha32. Volunteers for rare diseases- 3 years ....................................................... 34Iulia Jurca-Simina, Florin Jurca-Simina, Ionela Moaca, Pop Norbert, Berci Stefan, Iulia Popa Mihai Gafencu,MariaPuiu

POSTERS

CHANGING PHENOTYPES IN PRADER WILLI SYNDROME ....................................... 35Adela Chirita EmnadiTHE GROWING PATTERN IN A PATIENT WITH PRADER-WILLI SYNDROME AFTER GH THERAPY ................................................................................. 35Gorduza N.C., Braha E.E., Gorduza E.V.NEWBORN WITH HYPOTONIA AND DISTURBANCES OF ENDOCRINE-METABOLIC FUNCTIONS DIAGNOSES WITH PRADER-WILLY SYNDROME ................................... 36Monica Stoian, Maria Puiu, Simona Farcas, Nicoleta Andreescu, Marioara Boia, Valerica BelengeanuPERSPECTIVE DATA FOR CEPHALOMETRIC ANALYSIS AND ORODENTAL PATTERN FOR ROMANIAN PRADER-WILLI SYNDROME PATIENTS ......................................... 36Dragos Belengeanu, Angela Podariu, Monica Stoian, Maria Puiu, Dorica DanDIGESTIVE DISORDERS IN PRADER WILLI SYNDROME .......................................... 37Maria Pop, Maria PuiuEMOTIONAL AND BEHAVIOURAL PROBLEMS IN PRADER WILLI SYNDROME ................ 37Catana Andreea, Dronca Eleonora, Serban Simona, Miclea Diana, Pop Ionut, Felicia Petrisor, Pop I. VictorTHE IMPACT OF THE DIAGNOSIS AND DISABILITY ON THE FAMILY AND PERSON WITH PRADER-WILLI SYNDROME .................................................................. 38Dronca Eleonora, Catana Andreea, Serban Simona, Miclea Diana, Pop Ionut, Pop I VictorHEALTH ISSUES AND CONCERNS IN PRADER WILLI SYNDROME .............................. 38Serban Simona, Catana Andreea, Dronca Eleonora, Miclea Diana, Pop Ionut, Pop I Victor


A FEW WAYS TO MANAGE BEHAVIORAL DISTURBANCES IN PRADER WILLI SYNDROME .... 38Mariana Cojocaruc-FLIP REGULATION OF ENDOTHELIAL CELLS APOPTOSIS IN THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) – LIKE CONDITIONS ................................... 39Jeffrey Laurence, Radu StefanescuLOBAR HOLOPROSENCEPHALY-A RARE DISEASE ................................................ 40Marioara Boia, E.S. Boia, Maria Puiu, Dana Iacob, Aniko ManeaEFFECTIVE REHABILITATION TREATMENT IN A CASE WITH DOUBLE CHROMOSOMAL DELETION .............................................................................................. 40Dorina STOICANESCU, Mariana CEVEI ORAL MANIFESTATIONS INCLUDING GINGIVAL FIBROMATOSIS IN RARE DISEASES ......... 41Talpoş Ş, Puiu M, Talpoş C, Popa MCLINICA AND BIOLOGICAL CONFIRMATIONIN AN SUSPICION OF GLUT1 DEFICIENCY SYNDROME ............................................................................................. 41Dumitriu SimonaFROM A PARTICULAR PHENOTYPE TO A RARE GENETIC DISEASE – A PEDIATRIC APPROACH ............................................................................. 42T.Marcovici, I.Simedrea, G.Brad, L.Olariu, M.PuiuGENETIC COUNSELORS AND PREDICTIVE MEDICINE: A NEEDED PROFESSION IN ROMANIA ........................................................................................... 43Maria Puiu, Adela Chiriţă, Dorica DanASESSMENT OF MULTIPLE MALFORMATION IN NEWBORN. CASE REPORT ................. 43Belei Oana, Giurescu Ramona, Micle Ioana, Pop Elena, Marazan Monica, Simedrea Ioan, Puiu MariaA RARE CASE OF HEPATOMEGALY ................................................................44Maria Pop, I. Plesea, B. Farcasescu, M. Serban A NEW CASE 46,XX MALE SYNDROME ............................................................. 44Cristina GugRARE CAUSE OF HEMOPHAGOCYTIC DISORDER - CHEDIAK-HIGASHI SYNDROME-CASE REPORT ..........................................................................................45E. Boeriu, M. Cucuruz, M. Lelik, G. Brad, I. Ursache, A. Botiz, M.Puiu, M. SerbanPALLIATIVE MEDICINE IN RARE DISEASES - INTERFERENCE AND CHALLENGES ............ 45E. Boeriu, M. Cucuruz, S. Arghirescu, R. Costea, G. Brad, I. Ursache, M. SerbanPRIMARY IMMUNODEFICIENCIES - CURRENT DIAGNOSIS AND MANAGEMENT .............. 46Maria Cucuruz, Estera Boeriu, Mihaela Bătăneanţ, Giorgiana Brad, Maria PuiuTHE NEONATAL SCREENING FOR CONGENITAL HYPOTHYROIDISM IN TIMIS AREA – 10 YEARES OF EXPERIENCE ........................................................................ 46Otilia Marginean, Ioan Simedrea, Ioana Micle, Marilena Lesovici, Olaru GabrielaIlie Constantin, Maria Puiu, Roxana Gruescu, Elena Jivet, Tira Maria


reports (Following Congress Program)

1. PSyChiaTriC aSPECTS in PWS

Antony Holland,UK

PWS is associated with a specific risk for particular behaviour problems and for the development of psychiatric illness. These problems include; a) the development ofsevere over-eating behaviour starting in early childhood and persisting throughout life;b)amarkedtendencytoritualisticandrepetitivebehavioursandtotemperoutbursts;c)self-injuriousbehaviourintheformofskinpicking;andd)thedevelopmentofaffectivedisordersincludingdepressionandbipolardisordersandpsychoticillness.Thereasonsforthisandtheimplicationsforsupportandinterventionwillbereviewed.Keytointerventionisadetailedassessmentoftheindividualandtheircircumstances.

Communication

The7th Scientific conference of the International PWS Organisation took place in Taiwan in May 2010. New findings present at the conference included the following: a) investigations of the reasons for temper outbursts and how they may be linked to difficulties people with PWShaveshiftingtheirattentionfromonetasktoanother;b)observationsaboutchangesthatmayoccurinthefunctioningofpeoplewithPWSinlaterlife;c)familyandrelationshipissues;d)therelationshipbetweenPWSandautismspectrumconditions;d)researchontheeatingbehaviourincludingtheabilityofpeoplewithPWStofastaspartofreligiousobservance,therelationshipbetweeneatingbehaviourandcirculatingpeptides,andtwostudieslookingatthetreatmentoftheover-eatingbehaviour-theuseofexenatideandofvagusnervestimulation;e)theuseofdatabasestosupportPWSresearchandtoovercomethe limitations of research because PWS is a rare disorder; and f) an overview of thegenetics of PWS. These will be briefly discussed in the presentation.

2. nEWS abouT PradEr-Willi SyndromE. CliniCal rESEarCh PrESEnTEd aT ThE iPWSo ConFErEnCE in TaiWan 2010

Susanne BlichfeldtMD. Paediatric department. Glostrup University Hospital, 2600 Glostrup. Denmark [email protected]

Oralandposterpresentationsarereferred:Clinical researchconcerningsymptoms inneonates,appetiteandweightininfancyandchildhoodwillbedescribed.ConcerningendocrinologyinPWSare referred that both children and adults benefit from growth hormone treatment.


Testosteronetreatmentinadultmalesimprovesleanbodymassandselfesteemandisnotfollowedby behavioral problems. Thyroid function can be low. Adrenal insufficiency seems to be rare. Reflux is seen and dental problems are not rare. Body mass index can not be used for evaluation ofpercentageofbodyfatOverweightandmetabolicsyndromeiscommoninadults.Theroleofghrelinisdiscussed.Constipationandincontinenceiscommon.Orthopedicsymptomsbesidescoliosesareflat-foot, hip and other joint problems. Topics for actual clinical research are presented.

3. rESulTS oF ThE CarEgivEr’S ConFErEnCE in TaPEi

Hubert Soyer,Germania In retrospect of the Caregiver’s Conferences’ history, the main aspects of the conference inTaipei are highlighted. Examples of living, work and therapy show experiences in practicewith people with PWS in different countries. In addition the presentation gives a roughoverview of the Best Practice Guidelines for Standard of Care in PWS, developed in thepreviousconferencesinHerne2008and2009.

4. ThE romanian PradEr Willi aSSoCiaTion – PradEr Willi SyndromE a modEl For aPProaChing rarE diSEaSES in romania

Dorica Dan–president RPWA

AIM:Toassesstheresultsof7yearsofactivityofRPWAinRomaniainordertoensureanincreasedqualityoflifeforpatientswithrarediseases,usingthecomprehensiveapproachinthemanagementofoneofthesediseases:PWS.

ROMANIANPRADERWILLIASSOCIATIONrepresentspatientswithPraderWilliSyndromeandotherrare diseases in Romania, as well as their families and we wish to fight against the ongoing isolation that the health system, mass media, and scientific researchers in our country foster. The Romanian Prader Willi Association – RPWAwascreatedinMay2003,inordertobringtogethertheeffortsofpatients,specialistsandfamiliestoensureabetterlifeforallpeoplewithdisabilitiesproducedbyrarediseasesinRomania.OnOctober162005weopenedtheInformation Center for Rare Genetic Diseases. It is the first center of this type in Romania and we wish it to be a resource center for patientswithrarediseases,theirfamiliesandspecialistsinvolvedinthediagnosisandmanagementofthesediseases.

The access to information about diagnosis and management is essential and support groups ofpatientswhowentthroughsimilarexperiencesmayleadtoabetteracceptanceofthesituationand a more efficient approach of the disease.Weareawareofthefactthat,nomatterhowstrongandmotivatedparentsmaybe,theycannotsucceed by themselves to fight the disease. They need specialists and the understanding of the communitytheyarepartof.Themostimportantobjectiveofourassociationistoprovidesupportandunderstanding,counselingandaccesstoinformation,sothatnobodyfeelsaloneanymore.Through different projects, RPWA became more professional in providing socio-medical andeducational services for PWS and rare diseases. We are accredited for our services, provideauthorizedtrainingcoursesandweareaccreditedforresearchcapacityandforcontinuousmedicaleducation.

Throughimplementationoftheproject„Norwegiano–Romanian(NoRo)Partnershipforprogressinrarediseases”fundedbytheNorwegianCooperationProgramwithBulgariaandRomaniawearedevelopingtheservicesandcreatenewservicesforpatientswithrarediseasesinRomania.


StartingfromthemodelofPWSwhereweightmanagementandbehaviorinterventiontherapiesareessential, we have realized that these therapies and interventions would be efficient for many rare diseaseswithmotorretardation,obesity,hypotoniaassociatedwithcognitiveimpairments.Inourproject,webeganwiththeideathathealthandqualityoflifecanbeimprovedfor a wide range of rare diseasesifweaddressbehavioralproblemsandstarteffectiveweightmanagementprograms(a large part of rare diseases lead to neuro motor deficiencies and are aggravated by obesity and behavioral problems). Many genetic syndromes are associated with deficient disorders including autistictypebehaviors.Autismorautisticpsycho-behavioraltypebehaviorsoccurinmanygeneticdiseases (AngelmanSyndrome,Charge Syndrome,CohenSyndrome,Hartnup syndrome,Moebiussyndrome,PraderWillisyndrome,Toluenesyndrome,TuberousSclerosis,WilliamsSyndromeandanumberofstructuralchromosomalabnormalities).For all these patients there are not services at all in Romania.

Conclusion: We strive for and our projects include: timely diagnosis and correct application oftherapeutic and educational programs to alleviate specific manifestations of rare diseases to improve geneticaffectionstatusofthegrowthopportunitiesandpsychosocialintegrationofthesepatients.

5. PrESEnTaTion oF ThE ProjECT „norWEgian romanian (noro) ParTnErShiP For ProgrESS in rarE diSEaSES”Lázár Zsuzsa, RPWA, Zalau

The main goal of the Romanian Prader Willi Association is to increase the quality of life forpeopleaffectedbyPraderWilliSyndromeandotherrarediseases.Fromthebeginningthroughitsactivitytheassociationwasworkingtounitetheeffortsofpatients,specialistsandfamiliestoworktogetherforthisgoal.ThecomplexityoftheobjectivesandactivitiesoftheNoRoprojectmostlyfunded by a grant from Norway through the Norwegian Co-operationProgramme for Economic Growth and Sustainable Development in Romaniaoffersarealpossibilitytomakeimportantstepsin the field of rare diseases in Romania.

HavingaspartnerstheNorwegianPWSAssociation,FRAMBU–NorwegianCenterforRareDiseases,MinistryofHealthRomania,FoundationACASA,St.FamilyChurchZalau,CityHallZalau/DASC,CountyCouncilSalaj/DGASPC,RomanianMedicalGeneticsSociety,MedicalUniversityTimisoara,RomanianNationalAllianceforRareDiseases,weareworkingforthegoaloftheproject.

IntheprojectwecreatedtheNational Committee for Rare Diseases whichincludesrepresentativesofspecialists(doctors,psychologists,socialworkers,specialeducators),patientorganizationsandofthepartnersintheproject.ThisgroupevaluatedtheexistingsituationinrarediseasesfromRomaniaandproposedmeasurestoimprovequalityoflifeforpatientsaffectedbythesediseases.ThemaindocumentdevelopedistheNationalPlanforRareDiseases,whichwasforwardedtotheMinistryofHealthinordertobeadoptedandintroducedintheNationalStrategyforHealth.Wearealsocreatingnew servicesinrarediseasesbythePilot Reference Center for Rare Diseases.

Itwillprovideservicesinthreemaincomponents.• Adaycenter forchildrenwith rarediseaseswithbehaviorson theautistic spectrumwith

behavioraltherapyandweightmanagementunit.• Acomprehensivetrainingprogramforpatients,families,caretakersandspecialistsinvolved

in themanagementof rarediseases,using theFrambumodel.Groupsofpeoplewith thesame or similar diseases will come to participate on five days training programs offered by specialistsintopicsrelatedtotheirdiseases.MostofthesegroupswillbeabletoparticipateonthethreeweekrehabilitationprogramatAcasaFoundationbeforeoraftertheirtrainingperiod.


• Thethirdcomponentwillbededicatedtopatientsnewlydiagnosedandtheirfamiliestolearntocopewithnewsituationsmoreeasilybyreceivingcounselingandinformationaboutthediseaseandexistingservicesinthecountryandabroadfortheirdiagnosis.

In rare diseases information and training are essential in order to provide quality services indiagnoses,treatmentandrehabilitationofthepatients.Wecreatedauthorizedtrainingcoursesforspecialistswhoworkwithpatientswithrarediseases,andwearedevelopingaeUniverityinordertohavemoreaccessibleinformation.

Formanyrarediseasestherearenoeffectivetreatments,butagoodmanagementofthedisease,usingadequateservicescanprovideabetterqualityoflifeforpeopleaffectedbyrarediseases.

6. gEnEral hEalTh in PradEr-Willi SyndromE

Susanne Blichfeldt MDDepartment of Paediatrics. Glostrup University Hospital. 2600 Glostrup, Denmark

ObesitybecauseofhyperphagiaisthegreatesthealthriskinPrader-WilliSyndrome(PWS).OthersymptomsofPWSareimportanttobeawareoftoavoidseriousdiseasesituationsanddeathinyoungage.Severeinfectionswithoutfever,andminimalcomplaintsofpainbecauseoffracturesorintraabdominaldiseases,aretypicalsituationsinPWS,leadingtodelayofdiagnosesandtreatment.Othermedicalconditions,notrelatedtoweight,canbepoorvision,dentalproblems,intestinalproblemsincl.constipation,scoliosis,kyphoses,hypogonadism,osteoporoses,skinpicking,abnormalsleeppatternandpsychiatricdiseases.Weightrelatedproblemscanbeheartandlungdiseaseswithhypoventilationandsleepiness,incontinence,edema,skinulcers,jointproblems,diabetes,sideeffectsofmedicationandreducedmotorfunction.

7. romania: rESEarCh in rarE diSEaSES – ToTghEThEr and For PaTiEnTS

Maria Puiu, Mihai Gafencu, Natalia Cucu, Dorica Dan, Margit SerbanUniversity of Medicine and Pharmacy „V. Babes”, Timisoara, RPWA, Zalau

Inrecentyears,rarediseaseshavebecomeapriorityandamajorconcernoftheEuropeanParliament.It became increasingly obvious that thesepatients need support fromEuropean community.Allthe national single efforts in this field are not sufficient and those diseases are so rare, there we needcentersandexpertsineachEuropeanMemberState.InRomania,thegrowinginterestofthegovermentalhealthsystemisduetotherarediseasepatientsassociationseffortinthelast5years(APWRthenANBRaRo).

Buttheireffortshavetobecompletedbymedicals’community.Inthiscontext,agroupofRomanianprofessionals have initiated the research project ”Corelation of clinic, genetic and epigeneticaspectsimplicatedintheetiologyofPraderWilli/Angelmansyndroms:modelofmultidisciplinaryabordationforrarediseaseasinRomania”.

The project is remarcable because of the development of an efficient cooperation and partnership amongimportantinstitutionsformedicaleducation,universities,researchinstitutionandpatientorganisation (RPWA) in order to solve someproblems related to diagnostic, complex treatmentandpreventioninRD.ThenewinterdisciplinaryandpluridisciplinaryapproachofRDresearchinRomanianwillenssureabetterconnectionwithEuropean researchprojectsandwill contributeto optimization of the investigation methods, to a more efficient public health care sistem, with amajoreconomicandsocialimpactthroughshorteningtheperiodforapropergeneticdiagnose,hospitalisation,reducingthecostsandincreasingtheirchancesforintegrationintocommunity.

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ThroughthisprojectwillbeestablishedaCDInetworkwihexpertiseinRD,atEUstandards,improvingthecapacityforeducationandresearch.CoordinationofsuchcomplexteamsofresearcherswillfacilitatetheinitiationofnewcooperationininternationalresearchprojectsinRD.

Ourprojectpromotesanewmodelofpartnersipamongresearchersandpatientsandwillproveatnational level the efficiency of network approach in RD and cooperation for both, patient interest andresearch.

8. EPigEnETiC mEChaniSmS undErlying ThE imPrinTing dEFECTS: imPliCaTionS For ThE ESTabliShmEnT oF diagnoSTiC TESTing SChEmES For PradEr Willi SyndromE in romanian PoPulaTion

Natalia Cucu1, Gabriela Anton2, Maria Puiu3, Cosmin Arsene1, Anca Botezatu2, Corin Badiu4, Vasilica Plaiasu5, Daniela Nedelcu5, Radu Stefanescu5

1 University of Bucharest, Faculty of Biology, Dept of Genetics, Epigenetics Laboratory2 “Stefan Nicolau” Institute of Virology, Dept of Molecular Biology, Bucharest3 Medical and Pharmaceutical University Timisoara4 „N Parhon” Institute of Endocrinology, Bucharest5 Genexplore, BucharestClinical diagnosis of the Prader-Willi and Angelman syndromes remain difficult in many instances becauseofthe individualvariations inthephenotypeandbecausethephenotypedevelopsonlywithage.Knowledgeofthebasicgeneticdefectanditspossibleinheritance,butalsotherecentlydiscoveredepigeneticdefectanditsinheritanceisalsonecessaryforgeneticcounseling.About70%ofcasesareduetoa15q11-q13deletion inthepaternallycontributedchromosome.ThesedeletionsareoptimallydetectedbyFISHmethod.Theotheraproximately30%ofcasesofPWSareduetomaternaluniparentaldisomy(UPD),thatcanbestbedocumentedusingmicrosatelllitepobes.Lessthen2%ofcaseshaveanimprintingdefect,whichcausesnonexpressionofpaternalgenes in PWS critical region. This latter group is detectable through identification of parent-of-origindifferencesbyusingmethylationsensitiveSNRPN,aprocesscalled“methylationanalyses”.

Chromosomeanalysisbyclassicalkaryotypingmethodisusuallyaroutinepartoftheevaluationofthesepatients,inordertoruleoutotherabnormalities,andwillalsodetectrareinstancesoftranslocationsorotherchromosomerearrangements.Fromthepointofviewofgeneticcounceling,noneoftherecurrenceofPWSanditssistersyndrome,AS,haveinvolvedthetypicaldeletionorUPD,butratherhaveinvolvedtranslocationsandimprintingdefects.Also,themethylationanalysis,which confirm about 99% of cases without indicating the exact molecular mechanism, may be usedinprenataldiagnosis,providingtheknowledgeofthecorrectdevelopmentalstagewhentheimprintisestablishedinthegermline.

Imprintingandepigeneticreprogramminginmammaliangermcells,thezygoteandearlyembryosplaycrucialrolesinregulatinggenomefunctionsatcriticalstagesofdevelopment.Aberrantchromatinstates leading to aberrant gene expression patterns are determined by specific DNA methylation and histone modification processes (epigenetic modifications), as well as by the recently described activity of the ncRNA (noncoding RNA). They can occur secondary to a DNA sequence modification ormutationinacis-ortrans-actingfactororastrueorprimaryepimutationintheabsenceofanyDNA sequencechange.Primaryepimutationsoftenoccurafter fertilizationand lead to somaticphenotypemosaicism..IthasbeenestimatedthattherateofprimaryepimutaionsisgreaterthanDNAmutationsandactuallymaybeunderestimated.Knowledgeofthesocalled„openwindows”ofvulnerabilityofthegenomeduringthecrucialstagesofdevelopmentandtheirinteractionwiththe environment would be beneficial for the activities of establishment of optimal diagnosis and therapeuticorpreventiveschemes.

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9. ThE CyTogEnETiC invESTigaTion bEForE and aFTEr birTh

Gorduza E.V.1

1 University of Medicine and Pharmacy „Gr. T. Popa” Iaşi, Department of Medical [email protected]

The cytogenetic investigation (CI) identifies the number of chromosome and allows diagnosing the presenceofchromosomalabnormality.Thenormalnumberofchromosomeinhumansis46.Thecommonnumericchromosomalabnormalitiesaretrisomyandmonosomy.Thestructuralchromosomalabnormalities(SCA)arebalancedorunbalanced.ThebalancedSCA–inversionsandtranslocations-arecharacterizedbyanormalphenotypebecauseispresentonlyachangeofpositionofsomechromosomal fragments without any quantitative modification. The unbalanced SCA – deletions, duplications,isochromosomes,andringchromosomes–arecharacterizedbyanabnormalphenotypebecause is present a quantitative modification of some chromosomal fragments. The classical CI isbasedbyanalysisofhumancelldivision.Usually, thesecellsareobtainedafterashort (Tlymphocytefromblood–afterbirth)orlongharvest(amniocytes–beforebirth)followedbystopofdivisioninabichromatidianstage.Finally,thechromosomesaredisplayedonamicroscopeslideandareanalysedatopticalmicroscope.Thus,wecanidentifythenumericalandsomestructuralchromosomalabnormalities.Tooptimizethediagnosticofchromosomalabnormalitiesofsmallsizehavebeenimplementedmolecularcytogenetictechniques.ThemostcommontechniqueisFISH,based by a molecular hybridization between a fluorescent probe and a chromosomal target. Using thistechniquewerevealthepresence(normalstatus)orabsence(deletion)ofthechromosomaltarget.TheFISH techniquecanbeusedboth inprenatalorpostnatalperiodandhaveamajoradvantage in the short period (1-2 days) to obtain the final result.

10. EndoCrinE obESiTy in PradEr Willi SyndromE

Corin Badiu, Gabi MadarasNational Institute of Endocrinology, Bucharest, [email protected]

PraderWilli syndrome(PWS) isageneticdisorder (15q11-q13)characterizedby short stature,hypogonadismleadingtoosteoporosis,delayedpuberty,centralhypocorticismandthemost lifethreatening,excessiveappetitewhichisfollowedbymorbidobesity.

Patients with PWS present reduced GH secretion, hypogonadotropic hypogonadism, abnormalappetitecontrolandhighpainthresholdsuggestinghypothalamic-pituitarydysfunction.However,allhighresolutionimagingstudiesarenormal;duetochangesinChr15,thehypothalamicfunctionis disrupted. All patients with PWS show severe disturbances in appetite control resulting inhyperphagiaandobesity.

Peptidesinvolvedinhypothalamicappetitecontrolasghrelin,leptin,NPY/AGRP,POMC,andtheircognatereceptors,areinvolvedindevelopmentalprocesses,determinethethresholdforsignalsofbodyfatbelowwhichincreasesinenergyintakeandreductionsinenergyexpenditure.Inaddition,lowGHandIGF1level,centralhypothyroidism,delayedpubertyandcentralhypogonadismmayimpact upon the body composition. Despite the detailed knowledge about obesity mechanismsregulatedathypothalamiclevel,thepharmacologicalinterventionislimitedcurrentlytosubstitutionof proven endocrine deficiencies and GH treatment. ThePWSbrainseems“wired”forapositiveenergybalance,andveryfewpathwayscancounterbalancethisgeneticimprinting.

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11. nEurologiCal aSPECTS in PWSVioleta Stan, Emergency Children’s Hospital “Louis Turcanu” TimisoaraChildren with PWS show an unusual cognitive profile. They are often strong in visual organization andperception,includingreadingandvocabulary,buttheirspokenlanguage(sometimesaffectedbyhypernasality)isgenerallypoorerthantheircomprehension.Amarkedskillincompletingjigsaw puzzles hasbeennoted.Auditoryinformationprocessingandsequentialprocessingarerelativelypoor, as are arithmetic and writing skills, visual and auditory short term memory and auditoryattention span. These sometimes improve with age, but deficits in these areas remain throughout adulthood.

12. obESiTy and diabETES in PradEr Willi SyndromE (PWS)

Aurelia Szekely, Zsuzsa Lázár, RPWS, Zalau

Obesity is one of the defining characteristics of Prader Willi Syndrome.Ifnotdiagnosedinchildhoodbasedontheslownessofthefetalmovements,thehypotonia,themorphologicalappearance,obesityleadstothesuspicionofthediagnosis.

TherearemultiplecausesofobesityinPWS.Itischaracterizedbythefactthatitoccursprimarilyduetothepermanentappetite,aggravatedbythemusclehypotoniaandthepsychologicalstructureofthesepatients.

The fight against obesity in PWS should be permanent. In this struggle all stakeholders should beinvolved:family,doctors,socialcaretakersandpatientorganizations.Onlythiswaywecanpreventthemostseverecomplication,diabetesmellitus,which inevitably leadstoothermajorcomplications.

Oncediabetes installeditmustbepermanentlytreatedandweight lossbattlecontinueswithamoreseverediet,dailyexercise,physicaltherapytreatments,etc.Morbidobesityispreventable,canbereduced,sodiabetesmellitusanditsseverecomplicationscanbeavoided,assuringthiswayforthepatientswithPWSlongevityandmuchimprovedqualityoflife.

13. PradEr-Willi SyndromE rarE FaCTS CardiaC, rEnal and PoiSoning ComPliCaTionS

Gafencu Mihai, Gabriela Doros, Maria PuiuUniversity of Medicine and Pharmacy “V Babes”, Timisoara

Prader-Willisyndrome(PWS)isadisordercausedbyadeletionordisruptionofgenesintheproximalarmofchromosome15orbymaternaldisomyintheproximalarmofchromosome15.In1887,Langdon-Down described the first patient. PWS has long term consequences affecting the quality oflifeofthesechildren.Someparentsdonotthinkatallthelongtimeconsequencesanddoctorsmisstopreventother.Wewilldiscussprimarilyonthecardiovascularconsequencesofobesityandhypertensionandthenthekidneydamageandtheeffectofdrugsintherapy.Wewanttopresentaseverecaseofcardiaccomplicationsandonewithrenalfailure.

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14. rEduCEd dEEP SlEEP EFFiCiEnCy WiThouT ExCESSivE dayTimE SomnolEnCE in advanCEd and SEvErE ConComiTanT obSTruCTivE SlEEP aPnEa - hyPoPnEa and PradEr Willi SyndromE

Stefan Frent, Stefan MihaicutaUniversity of Medicine and Pharmacy “V Babes”, Timisoara

Weevaluateda21yearsoldfemale,refferedfromGeneticDepartmentatV.BabesSleepLabinTimisoara,Romania,diagnosedwithPraderWillisyndrom.150cm/105kg(BMI46,66kg/m2),neckcircumference39cm,abdominalcircumference121cm,hipcircumference141cm,bloodpressure120/70 mmHg, reported apneas, no snoring, Epworth Sleepiness Scale 3, no excessive daytimesomnolence,seldommorningheadache,disturbedsleep,onenicturiapernight,2-3awakenings,normaluvula, tonsils, septum,Malampati III, treatedwithLevotiroxin (hipotiroidism), fullnightpolysomnography.

Polisomnography:timeinbed523min,sleepperiodtime(SPT)488,5min,wakebeforsleep32min,wakeduringslepp19,5minute,Sleeponset32min,totalsleeptime(TST)469min,R(REM)55min, N (Non REM) duration 416 min, slow wave sleep (SWS) duration 78,5 min, sleep efficiency N1 (100 x TST/TIB) 89,7%, sleep efficiency N2 (100 x TST/SPT) 96%, sleep efficiency N3 (N3+ REM/TST) 28,5%,AHI54.8/h,central0,5/h(meandurationMD13,4sec),obstructive6/h(MD12sec),mixed0,1/h(MD12sec),hypopneaAHI48,1/h(MD16sec),periodicbreathingtotalduration1,57min(0.3%ofsleep),centralapneatotalduration1,68min(0.3%ofsleep). MeanHR(BPM)88,6±6,89,averageoxygensaturation96%,desaturationindex27,2/h,maximdesaturation45sec,meanoftheresp.eventSpO2minlevels93%,meanoftheresp.eventSpO2minlevelswithdesat92%,minimumoftheresp.eventSpO2minlevels79%,lowestSpO2 (≥2 sec) 79%, arousal index 5,8/h sleep.

AsymptomaticpatientswithPrader-Willisyndromeshouldbeevaluatedforsleepdisordersatanage sufficiently young before the development of the syndrome related obesity.

15. rECommEndaTionS For ThE diagnoSiS and managEmEnT oF PradEr-Willi SyndromE. EFFECTS oF groWTh hormonE ThEraPy in ChildrEn

Dana Liana David, Raluca Dumache University of Medicine and Pharmacy „V Babes”, Timisoara

Sincethecommercialreleaseofrecombinanthumangrowthhormone(GH)in1985,therapeuticuseofthismedicationhasbeenstudiedinavarietyofmedicalconditionsandgeneticsyndromes.GH was first approved by the EMEA for use in children with PWS in the year 2000. Currently,60%of the individuals in thePWSdatabase (WHO)are receivingGHtherapy.Currentconsiderations regarding the use of GH treatment in PWS can be divided into the followingcategories:

1.GHtreatmentofinfants/childrenwithPWStoimprovebodycompositionabnormalitiesandimprovelineargrowth.

2.GHtreatmentofadultswithPWSto improvebodycompositionabnormalitiesandimprovebonemineraldensity.

GHshouldnotbeasubstituteforappropriatenutritionalintakeandphysicalactivity.

Thefollowingphysicalchangesweredocumentedinvariousresearchstudies,andthemostdramaticresults were reported in the first year of GH treatment. Studies in Sweden and the United States followedchildrenbeyondoneyearoftreatmentandreportedsomeadditionalimprovements:


•Increasedheightandgrowthrate—•Increaseofhandandfootsizestonormalproportions—•Decreaseinbodyfat—•Decreaseinbodymassindex(BMI)—•Increaseinmuscledevelopment—•Improvedrespiratoryfunction—

Thecomplexgenetics,etiology,multiplephenotypes,andevolvingnaturalhistoryofPWSmeansthat a multidisciplinary professional, parental, societal, and environmental approach to themanagementisrequiredwithmanychallengestoreducingmorbidityandmortalityandimprovingqualityoflife.However,overrecentyears,anincreasingappreciationandavailabilityofimportantmanagement strategies have already made significant improvements in the life of those with PWS, e.g.earlydiagnosis,useofmultidisciplinaryteams,introductionof GHtreatment,controlofthefoodenvironment,andbetterunderstandingofthebehavioralandpsychiatricaspects.

16. orThoPEdiC and SurgiCal FEaTurES in PaTiEnTS WiTh PradEr Willi SyndromE

Popoiu MC1, David VL2, Boia ES1, Maria Puiu1

University of Medicine and Pharmacy “Victor Babes” TimisoaraEmergency Children’s Hospital “Louis Turcanu” Timisoara

Prader-Willisyndrome(PWS)isacongenitalchromosomaldisorderconsideredthemostcommongeneticcauseofmorbidobesity.IninfantsthefeaturesofPWSincludeinfantilehypotonia,feedingdifficulties, mental deficiency. Older children are characterized by obesity, hypotonia, short stature, hypogonadism,andbehavioralabnormalities.UsuallyPWSisnotdiagnoseduntilrapidweightgainleadingtoobesity.FeaturesinpersonswithPWSsuggestahypothalamicdysfunction:hyperphagia,sleep disorders, deficient growth hormone secretion, and hypogonadism. PWS patients suffer from variousmedicalconditionsthatrequiretheattentionofmanyprofessionals.

This presentation focuses on the possible medical condition that requires the involvement ofa surgeon. In infants with PWS generalized hypotonia lead to weak suck reflex requiring often nasogastric tube-feeding even gastrostomy. Genital hypoplasia and cryptorchidism are constantfindings in PWS boys and the justification for and timing of surgical exploration and orchiopexy are controversial. Gastric dilatation, abdominal and rectal pain, rectal fissures, hemorrhoids, andrectalbleeding(brightredblood)mayoccurandrequiretreatmentinsurgicalcompartment.GastrointestinalpathologyisthemostimportantfeatureofPWS.ObesityisthemajorfeatureofPWS. The primary health issues in PWS are exacerbated by obesity and related findings. Obesity can becomelife-threateningifnotcontrolled.SurgicaloptionsforweightmanagementarenotgenerallyrecommendedinPWSbutbariatricsurgeryshouldbeconsideredinseverecases.Musculoskeletaldisorders like scoliosisarealsouniversal featuresofPWSandconsultationwithanexperiencedorthopedist is essential. Scoliosis occurs in about 40% of the patients with PWS and is treatedmainlybynonsurgicalmeasures.Regularphysicalexercisescorroboratedwithphysiokinetotherapybesidesimprovingthespinalcurveincreasethemuscletonusandhelpmaintainingbodyweight,andcancontrolthescoliosisinupto90%ofthepatients.Osteoporosisisanimportantfeatureinthis patient often leading to pathological fractures of the long bones, with difficult treatment and poorprognosisduetothemorbidobesityandlowpatientcompliance.InconclusionweconsiderdespitethefactthataprimarycarephysiciansshouldbeabletotreatmostpatientswithPWS,thesurgeonandtheorthopedistshouldhaveaplaceinthemultidisciplinaryteamneededtotreatindividualswithPWS.


17. ThE imPaCT oF ThE naTional PlanS on ThE liFE oF PEoPlE living WiTh PradEr-Willi SyndromE in FranCE

Christel Nourisier, Franta, BoD EURORDIS,EU CERD member

In France as in many other European countries, people born with Prader-Willi syndrome haddifficulties in obtaining correct diagnosis, and were facing unequal access to care (Eurordis Care studies2002-2008:Thevoiceof12000patients*).Clinicalpathwayswerebasedonindividualchoice,geographicalsituationorchance.Accessandreimbursementoftreatmentsanddrugs,socialandfinancial compensation of disabilities were extremely diverse or inexistent. No epidemiological dataorsurveillancewereavailable.

13familiescreatedanassociation,Prader-WilliFrance,in1996.PraderWilliFrancebringstogether655members in2010. In2000,Prader-WilliFrancewasafoundingmemberofAllianceMaladiesRares,theFrenchumbrellaassociationforrarediseases,andalsobecamememberofEURORDIS,theEuropeanorganisation.

6000to8000rarediseasesspeakingwithonevoiceatNationalandEuropeanlevelwereheardbytheFrenchauthorities.Rarediseasesbecamevisibleasaseriouspublichealthissueinthepublichealthlawadopted in France in 2004. The aim of the first National strategic Plan was: « ensuring equity in the access to diagnosis, treatments and provision of care ».TheFrenchNationalPlanfor rare diseases (2005-2008) was in first one in Europe.

At the end of this first plan, and after an in depth evaluation of its outcomes, the Ministries of Health,Research,SocialAffairsandEmployment,togetherwiththepatientassociationsandotherstakeholders,arepreparingasecondplantofurtherextendandstrengthentheprogressesofthefirst plan, and build up sustainability. It will be announced before the end of the year 2010.

HowhasthedailylifeofthepeoplelivingwithPWSbeenimprovedinFrancefrom2004to2010?• easier andbetter access todiagnosis and treatment,with thedesignation and fundingof

centres of reference, then of a network of centres of competence to cover the nationalterritory.Thecentresprovidediagnosisandcoordinatecarefrombirthtotheendoflife.

• developmentofeasilyaccessibleinformationbytheassociationandthecentresofreference:websitesoftheassociationandofthecentreofreferenceinToulouse,articlesin.Orphanet,MaladiesRaresInfoServicehelpline:booklets„Iamgoingtoschool”,„earlymanagementfrom0to6years”,„managementofbehaviourproblems”,publishedbyPrader-WilliFrance….

• emergencyandcareindividualcardsthatpeoplecancarryallthetimeandpresent,whennecessary

• nationalprotocolfordiagnosisandcareusedasabaseforreimbursementbytheFrenchSocialSecurity system. Treatments can be reimbursed without specific marketing authorisation, if prescribedbyacentreofreferenceorcompetence(ex:antinarcolepsydrugs,breathingaidsduringthenight)

• improved financial and social compensation of disabilities, specific needs better taken into consideration.

Challengesofthenextplan!2011-2015• to better link specialised care to proximity care• tobettertrainallhealthprofessionals,particularlyparamedicalandsocialworkers• therapeuticeducationofpatientsandfamilies• clinicaldatacollectionforpublichealthandresearch:howtomeasurelifeexpectancyand

qualityoflifeimprovements,usingacommoncoding(Orphacode,thenICD11)andalongterm funded register?Howtomeasure theachievementsofPlans in termof reductionofhealthcareandcompensationofdisabilitycosts,nottomentiontheburdenofthediseaseson


thefamilies(reducedemploymentopportunities,absencesofworkofcarers,inducedstressanddiseases…)

• moreEuropeanpartnershipsforbasicandclinicalresearch,Europeanguidelinesformedicalandsocialcare.

*Thevoiceof12000patientswww.eurordis.org

18. PSiChiaTriC aSPECTS in PWS

Antony Holland, Cambridge, UKPsychiatric aspects in PWS

PWS is associated with a specific risk for particular behaviour problems and for the development ofpsychiatricillness.Theseproblemsinclude;a)thedevelopmentofsevereover-eatingbehaviourstartinginearlychildhoodandpersistingthroughoutlife;b)amarkedtendencytoritualisticandrepetitive behaviours and to temper outbursts; c) self-injurious behaviour in the form of skinpicking;andd)thedevelopmentofaffectivedisordersincludingdepressionandbipolardisordersandpsychoticillness.Thereasonsforthisandtheimplicationsforsupportandinterventionwillbereviewed.Keytointerventionisadetailedassessmentoftheindividualandtheircircumstances.

Communication

The7th Scientific conference of the International PWS Organisation took place in Taiwan in May 2010. New findings present at the conference included the following: a) investigations of the reasons for temper outbursts and how they may be linked to difficulties people with PWS have shifting their attentionfromonetasktoanother;b)observationsaboutchangesthatmayoccurinthefunctioningofpeoplewithPWSinlaterlife;c)familyandrelationshipissues;d)therelationshipbetweenPWSandautismspectrumconditions;d)researchontheeatingbehaviourincludingtheabilityofpeoplewithPWStofastaspartofreligiousobservance,therelationshipbetweeneatingbehaviourandcirculatingpeptides,andtwostudieslookingatthetreatmentoftheover-eatingbehaviour-theuseofexenatideandofvagusnervestimulation;e)theuseofdatabasestosupportPWSresearchandtoovercomethelimitationsofresearchbecausePWSisararedisorder;andf)anoverviewofthe genetics of PWS. These will be briefly discussed in the presentation.

19. EThiCal managEmEnT oF PaTiEnTS WiTh PradEr-Willi SyndromE aCroSS liFE SPan

Violeta Olivia StanUniversity of Medicine and Pharmacy “V Babes”, Timisoara

It is absolutely critical to have families, health care providers, communities educated about the physiologic, medical, and behavioral characteristics of the adult with PWS in order to avoid abuses. Therefore, from an ethical and legal point of view is essential to determine the capacity of a person with PWS to make decision about his/he eating behavior and if the patients lack this capacity, the common law principle is to act in the “person’s best interests” in the least restrictive alternative, respecting the individual. Allowing serious weight gain and the serious health consequences is an abdication of responsibility from parents and health care providers, not a paternalistic approach. Physicians have the due to consider all these aspects of managing individuals with PWS, especially in an age specific manner. Resource professionals and centers should be able to provide education, counseling and supervision at different levels of intervention


Prader-Willisyndromerequiresamultidisciplinaryapproachtodeliveryofcare.Thesyndromeisoftendiagnosedintheneonatalperiodbutinmanycasesisnotsuspecteduntillaterinchildhoodwhentheonsetofobesityisoccurring.Therefore,thereisneedforacombinationofnutritional,medical,andbehavioralapproachedbasedontheageofindividualsdiagnosedwithPrader-Willisyndrome.Theneedsofeachagegroupshouldbeaddressseparately.

NEONATAL: During the first month of life, Prader-Willi babies are hypotonic, do not wake to be fed andareingeneralunresponsive.Theycanalsopresenthypothermiaandhypogonadism.Therefore,providinganadequatenutrition,dietary fat forbrain growthanddevelopment is essential andrepresents the main concern for the management of the disease in the first month of life. For parents,itisimportanttoprovidecounselingtoassurethatthebabieswillreceiveandmaintainthepropernutritionandearlysupportinenhancingobservationalskillsforobservation.

ONE MONTH TO 24 MONTHS: A close attention is required to continue assuring an adequatenutritionaccordingtonormalnutritionalguidelines.Inaddition,programsofphysicaltherapyanddevelopmentalstimulationshouldbeinitiatedbecausedevelopmentdelaysarecommoninchildrenwithPrader-Willi.Familycounselingshouldbeprovidedtoemphasizethe importanceofnormaldiet and appropriate weight gain during the first 2 years of life and neuro-motor stimulation.

TWO TO FIVE YEARS:Duringpre-schoolyears,the insatiableappetitebecomesapparent inthemajorityofchildrenwithPrader-Williandmanychildrenbecomeobeseduringtheseyears.Thus,lowcaloriedietsarenecessaryandsupplementalvitaminsandcalciumshouldbeassured.Developmentaldelayscontinuebutsomeimprovementcanbeseen.Withprogramsthatenhancecommunicationskills, appropriate social interactions andphysical and speech therapiesmanyproblems canbeaddressed.Behaviorproblemsandemotionallabilitymaybecomeaproblemparent’ssupportgroupandprofessionalsupportmaybeplanedtohelpfamiliesSiblings,extendedfamilymembersandallcaregiversrequireeducationandcounselingtoassureappropriateactions,includingthefoodrestrictionnecessaryforchildren

SIX TO 11 YEARS:Weight control at this age is essential in order to avoid uncontrolled eatingand obesity. This may require locking food within the home and restriction of excess fluids. Also, teachersandotherschoolpersonnelshouldbeeducatedtotheneedforclosesupervisionofPrader-Willichildrentoinsureadherencetoadiet.Aregularprogramofphysicalactivityisalsoessentialtoweightmaintenance.Inaddition,behavioralandsocialchallengesoccuruponenteringschoolsothatconsultationwithbehaviorspecialists,psychologiststogetherwithpsychotropicmedicationmaybehelpfulinmanypatients.Educationalgoalsrequireprovisionofopportunitiesforsuccessthat aredevelopmentally rather thanageappropriate.Many children require special educationbutthiscanbemixedwithsomemainstreamactivities.Educationofextendedfamily,educators,neighborsandcommunityisessentialbecausechildrenwithPrader-Willisyndromecanfrequentlymanipulate neighbors, friends and strangers into providing food. Siblings may require specialsupportandcounselingtobeabletoadjust.

TWELVE TO TWENTY ONE YEARS:Adolescenceisatimeoftransitionforallchildren.AdolescentswithPWSbecomeawareofthedifferencesbetweenthemselvesandtheirpeers.Thus,maintainingareasonableweightwheresharingfoodisasocialactivitycreatesfrustrationandcontinuestobeachallengeforfamilies.Recommendationsforcaloricrestrictionsshouldbebasedonlineargrowthandingeneralcaloricrequirementsareusually lessthantheestimatedneedsofadolescentsofcomparableheight.Exerciseprogramsshouldbeapartofdailyactivities,andsometimesone-toonesupervisionduringtheschooldayissometimesnecessary.Increasedirritability,agitation,loudspeech,uncooperativeness,rigidity,andperseverationcanbeobservedduringtheseyearssothatpsychiatricandpsychologicalinterventionisoftennecessary.Regardingeducation,childrenwithPrader-Willisyndromeshouldbeplacedinclassroomsbasedonintellectualfunctionandbehavioralneeds.On-site community vocationalplacements shouldnot include food-relatedworkbecausedespiteclosesupervision,childrenwithPrader-Williwillattempttoobtainfoodateveryopportunity.


The teaching should focus on training for specific living and social skills because of the inability of theseindividualstoliveindependentlyinanunsupervisedsetting.Itisessentialtohavefrequentcommunicationbetweenhomeandschooltobeabletomanagebehaviorofthesechildren.Duringthistimelegalguardianshipbecomesanimportantconcern.Parentsneedhelptoacknowledgethattheirchildrencannotlivealifefullyindependentbecauseoftheinabilitytomanagemoneyandcontrolfoodconsumption.

ADULTHOOD (Over 21 years):Asforanyindividualwithdevelopmentaldisabilities,forpeoplewithPrader-Willi the transition from childhood to adulthood is difficult. People with PWS now live longer andparentshavethesameincreasedresponsibilityfortheirchildrenwithspecialneeds.Meaningfulworkforthesepeoplerequiresspecialconsiderations.Themajorhealthproblemistheobesity,whichwas associatedwith serious complications like type IImellitus, profound hypoventilationandapnea,hypertension,osteoporosis,skinirritations,fractures.Theneedforsocialinteractionsincreaseandthedesiretoliveindependentlycontinuesandtheenvironmentshouldbepreparetoprovideitinethicalmanner

20. ParTiCular FormS oF PradEr Willi SyndromE – CliniCal and gEnETiC STudy

C. Rusu, C. Vulpoi, E. Braha, M. Volosciuc, I. Ivanov, C. Gorduza, V. Gorduza, M. Puiu, D. Dan

Prader–Willisyndrome(PWS)isarelativelycommondisorderduetoabnormalitiesinthe15q11.2-q13region.Majormanifestationsincludehypotoniawithpoorsuckandpoorweightgainininfancy,earlychildhood-onsethyperphagiaandobesity,characteristicappearance,hypogonadism,growthhormone insufficiency causing short stature, mild mental retardation and characteristic behaviour.We present 3 particular cases of PWS recorded in the files of Iasi Medical Genetics Center in order toillustratesomespecialfeaturesandtodiscussthediagnosisandmanagementstrategy.Inall3casesthesuspicionofdiagnosiswasbasedonactualizeddiagnosticcriteria.

Case 1:10yearsoldgirlwithtypicalneonatalhypotoniaandpoorweightgainininfancyfollowedbymarkedhyperphagiaandobesity,acromicriaandhypogonadism,butwithtallstature,multiplesevere allergies, severe mental retardation and seizures. Genetic defect: microdeletion identified byFISH;

Case 2: 6 years old girl with neonatal hypotonia and feeding difficulties followed by marked obesity,butwithmacrocephaly,inexpressivefaceandseveretibiavara.Geneticdefect:imprintingdefect;

Case 3:20yearsoldboywithtypicalneonatalhypotoniaandpoorweightgainininfancyfollowedbymildobesityandrelativelynormalapetite,acromicria(butwithshorteningofthe4thmetacarpal)and a particular psychological profile. Genetic defect: 15q deletion identified on the karyotype.Clinicalfeatures,diagnosisandmanagementwillbeillustratedindetail.Inconclusion,wepresent3particularcasesofPWSinordertoillustratesomespecialfeaturesandtodiscussthediagnosisandmanagementstrategy.

21. nuTriTion managEmEnT in PradEr Willi SyndromE

Adela Chirita,University of Medicine and Pharmacy “Victor Babes” Timisoara

ThemanagementofPraderWilliSyndrome(PWS) involvesamultidisciplinary life-longapproachtoimprovequalityoflife,preventcomplications,andprolonglifeexpectancy.EarlydiagnosisofPWS,beforetheoccurrenceofobesityisextremelyimportantforinitiationofprecociousnutritionprogram.Preventionandtreatmentofobesityisessentialanddependsonalow-energyandwell-


balanceddietwithrigoroussupervisionandrestrictionoffoodaccess,combinedwithregularmealsandexercise.AneffectiveWeightControlSystemis“TheRed,Yellow,Green”System.Usinganindividualizeddailymealplan,caloriesarecontrolledbydividingfoodintolow,moderateandhigh-caloriefoodgroups.Onelearnsto„go”withsomefoods,„becautious”withsome,and„stop,”withstillothers.

22. PradEr-Willi SyndromE and PhySioThEraPy

Giltvedt, Kaja and Lisen MohrFrambu Resource Centre for Rare Disorders, Oslo [email protected]

Inthelastdecade,NorwegianpaediatricianshaveacquiredmoreknowledgeaboutPWSandmostchildrenbornwith the syndromearenowdiagnosed in theneonatalperiodusinga DNAbloodtest.Restrictedenergyintakeandincreasingenergyconsumptionwithdailyexercisesandphysicalactivityarethemostimportanttasksforcaretakersofchildren,youthandadultswithPWS.ItisalsoofmostimportancetosupporttheparentstohandlelivingwiththestressofhavingapersonwithPWSinthefamily.MostchildrenwithPWSinNorwaystartgrowthhormonetreatmentfrom1-2yearsofage.

The presentation will cover different topics as how to stimulate to aid development in the first yearsoflife,exampleonhowtofollowupinschoolandalsointheyouthandgrownupperiodoflife. Exercise and physical activity have many benefits. It strengthen muscles, increase endurance, flexibility and co-ordination , keep the heart healthy, bones strong and improve mood and decrease feelingsofdepressionandanxiety.

Encouragementandmotivationfromthecaretakersandparentsareimportantinordertogetthepersontoparticipateindifferenttypesofphysicalactivitiesandsports.Thepresentationwillshowdifferentwaysinwhichthiscanbeachieved.Exerciseandphysicalactivityshouldbeincorporatedintodailylife.BothparentsandcaretakersshouldsetagoodexampleforthepersonwithPWSbyalsopractisingbeingphysicalactive.

The presentation will be illustrated with pictures and short video films.

23. TranSiTion To adulThood: WhaT iS a good liFE For PErSonS WiTh PWS?

Arnesen, R.O.The Norwegian PWS Association, [email protected]

Weallwantourchildrentobehappy.Wealltrytogivethemagoodlife.TogiveourchildrenwithPWSagoodfuture,asfarasweareableto,isachallengingtask.Theparentsarethemostimportantpartofthechildren’slife,andtheyneedknowledge.Closecooperationwithprofessionalsis important;Parentsandcaregiversneedtheir support.Sharingexperiences,betweenparents,family,caregiversandotherprofessionalsisofutmostimportance.

DoesapersonwithPWSreallyhavechoicesforherownfuture?Howcanourchildrenliveindependentlives–willtheyeverbeabletomanagetheirownlife?Whataboutfoodandmoney?Whataboutajob,oractivitiesduringthesparetime?Howandwhereshouldtheylive?I will talk about the difficult transition between school time and adulthood, based on experiences from Norwayandwhattheparentsandcaregiverslearnthroughtheservicesprovidedfromthenationalresourcecentre,Frambu.Rules,regulationsandagreements,withinaframeofcodeterminationandpersonalfreedom,isthewaywehavetogo.


24. undErSTanding and managing EduCaTional iSSuES in PradEr-Willi SyndromE

Amalia Raluca SabăuPsychologist, The Romanian Prader Willli Association

Itisimperativeforteachers,therapistsandotherschoolpersonnelwhoworkwithchildrenwithPrader-Willi syndrome to gain knowledge about this disorder as well as educational issues andoptionsinordertomaintainconsistencyintheeducationalarea.Thispaperprovidescomprehensiveinformation associated with providing educational opportunities to these children and offerspragmaticsuggestionsandstrategiestohelpprofessionalstocreateasuccessfullearningexperienceforchildrenwithPWS.Wheneducatorsunderstandeachchildasanindividualwithspecialstrenghtsandneeds,theycanprovideaneducationthatisappropriatetohisneeds,theycandeterminehowtheattributesofPWScancontributetosuccessandcanassistchildrenandfamiliestocopewiththe challenges associated with the presence of the syndrome and maximize their functioning,independence and happiness. Working together we can find the best way for children with PWS to succeedinschoolanexciting,stimulating,positiveexperience.

25. bEhavioral inTErvEnTionS in PWS

Simona DumitriuUniversity of Medicine and Pharmacy “Victor Babes” Timisoara

AlmosteveryonewithPrader-Willisyndromepresentswithbehaviourwhichcanbringchallengestoeitherthemselves,orthosearoundthem,orboth.Behavioural challenges varies considerably between individuals from very mild to very severe,andeachindividualmaydisplaydifferingbehaviours.Theseinturnmayvarywithage,externalenvironmentandemotionaldevelopment.Thedegreeof learningdisabilitydoesnotnecessarilyaffecttheseverityofbehaviouralchallenges.Thosewhohaveonlymildlearningdisabilitiesarejustaslikelytohavechallengingbehaviourasthosewithaseverelearningdisability.

Forpsychiatrists,more importantthanpreviousexperience is awillingnessto learnaboutthemanagementoftheclinicalfeaturesofPWS.PatientswithPWSwillrequiremoretimefortheinitialevaluationandwillneedtobecarefullymonitoredandseenwiththeirparentsorcaregivers,astheseinformantsprovidedataregardingpresentingproblems,environmentalstressors,concurrentmedicalproblemstimelines,etc.PatientswithPWSoftenhavelimitedinsightorsocialjudgment,andwhile theycansharetheir thoughtsand feelings, theyneedhelp identifyingmoreabstractinformationrelatedtotreatmentgoals.

ManyguidelinesusedtotreatpeoplewithintellectualdisabilitiesingeneralalsoapplytothosewithPWS.Inthispopulation,forexamples,behavioralorpsychiatricepisodesmayrelatetountreatedpainormedicalconditions(e.g.,constipation,UTI,dentalcaries),changeindailyroutines(e.g.,ateacherisill,activitiesarenotasplanned),oremotionalupsetsrelatedtolossorchange(e.g.,petdies,staffmembermoves,exaggeratedgriefreactions).

Additionaltipsthatoptimizepsychiatricworkinthosewithintellectualdisabilitiesinvolvebasiccommunication. It isoftenbest, forexample, to take the lead fromparentsas tohowtobestcommunicatewiththepatient,tousesimplewords,speakslowlywithoutshouting,usevisualsasneeded,andtalkdirectlytopatientsinsteadofreferringtotheminthe3rdpersonwhileinearshotoftheirparentsorstaff.ThepersonalitystrengthsandhobbiesofthosewithPWScanalsobeusedintheserviceoftheirtreatment.

BehavioralinterventionsareacriticalfeatureoftreatmentinPWS;theyshouldbetriedbeforepsychotropic medications are used, and in combination with all medication trials. Functional


behavioralassessmentsorinputfromanappliedbehavioranalystmaybehelpful,butmostlikelythegoalofinterventionistoaltertheenvironmentalconditionsratherthantoexpectthepersonwith PWS to change. The individual’s unique attributes such as personal interests and hobbiescanbeused in theserviceof treatment.ThegoalofbehavioralassessmentsmaybetochangetheenvironmentalconditionsratherthanexpectingthepersonwithPWStochange. Inadditiontoan individualizedbehavioralplan,moregeneral supports thatworkwell inpeoplewithPWSincludedailyroutines,visualschedules,andpositiverewardsinsteadofpunishments.Behavioraland environmental interventions should be used for problematic syndromal behaviors beforepsychotropicmedicationsareconsidered,andtheyshouldaccompanyallmedicationtrials.

26. arT ThEraPy aCTiviTiES For ChildrEn and adolESCEnTS WiTh PradEr Willi SyndromE

Mihaiela Fazacas, Emese DarkoAPWR

Prader Willi Syndrome is a rare genetic disorder characterized by cognitive and adaptive deficits, sexual immaturity, poor gross motor skills, emotional instability and behavioral disturbances.Thepsychotherapeuticprocessneedtoaddresstheemotionalandbehavioralproblems,mustbeadaptedtolearningstyle,cognitiveabilities,memoryandattentionspanofpatientswithPWS.Sothese activities should be more specific in order to be effective. Art therapy represent a way to help patientswithPWS(aswellforotherpeoplewithdisabilities)toencountertheworldwithoutfear,to express negative emotion in a „positive” way, to develop self-image and confidence, implication andcooperationetc.

This paper presents the benefits of art therapy activities for children and adolescents with Prader Willi Syndrome using our experience in this field.

27. nurSing aSPECTS For PWS PaTiEnTS

Livia Berinde, Claudia GoronRehabilitation, Treatment and Care Center “ACASA” Zalau, RomaniaINTRODUCTION: Many of rare diseases are inadequate treated due to the lack of knowledge.Knowingrarediseasescharacteristicsandtheirconsequencesinmedical,psychologicalandsocialareasleadstopropercareandtreatment.

PRESENTATION:PWSisararegeneticdiseasewhichaffectsbothgenders.PWSpatientshavecommonfeatures,differentfromanindividualtoanotherandwhichchangeoncewithaging.Inrelationwiththemainsymptomsandfunctionalconsequences,thePWSpatientpresentsspecialaspectsinthenursingplan:alimentationparticularities,adifferentwayofpainperception,bodytemperatureparticularity,respiratoryanddigestivedistinctproblems,behaviorproblemsandothers.Knowingthis special aspects may influence in a positive way, the prognostic.


28. diSEaSE SPECiFiC rEhabiliTaTion in PradEr-Willi SyndromE

Emanuele Grolla1, Gilberto Andrighetto1, Pietro Parmigiani1, Uros Hladnik1, Gabriela Ferrari1, Roberta Bernardelle1, Martina Dal Lago1, Anna Albarello1, Giuseppe Baschirotto1, Giuseppe Filippi2, Roberto Lovato3, Diego Dolcetta1

1 “M. Baschirotto” Institute for Rare Diseases - B.I.R.D., Centro Diagnostico Riabilitativo per la Diagnosi Terapia e Cura delle Malattie Rare, Costozza di Longare-Vicenza, Italy2 „Camillo de Lellis” Hospital, Department of Rehabilitation “Alto Vicentino”, ULSS4-Schio, Italy; 3 „Villa Berica” Hospital, Vicenza, Italy

INTRODUCTION: Our study represents an attempt to respond to what we felt was an insufficiently heard social need:weight control in the late teen-ager and adult PraderWilli syndrome (PWS)population. For this reason we set up a rehabilitation approach based on periodic residentialrehabilitation cycles specifically customized to Prader Willi syndrome patients (PWRs).To review the efficacy of a multidisciplinary rehabilitation approach for weight control in adult patientsaffectedbyweanalyzedretrospectivelydataobtainedduringtheperiod2002-2008.

METHODS:Weanalyzed53PWSsubjectssufferingfromsevereobesity.AmultidisciplinaryapproachwasusedtoreduceobesityinadultPWSpatients.A1500Kcaldailydietisassociatedwithintensephysicalexerciseduring4weekcyclesorganized4timesayear.Endurancetophysicaltrainingwasachievedbymusictherapy,psychomotricity,educationalandentertainmentactivities.

RESULTS: BMI decreased on average by 2.1 points (standard error of the mean, SEM 0.16) pertrainingwhenPWSsubjectsattendedtherehabilitationtreatmentfor4weeks.In3patientswhoattendedourtreatmentsregularly,werecordedaBMIreductionof8.9(SEM4.2)over6years.Weobserved a statistically significant gender difference in weight loss during the treatment and a trend inweightgainafterdischarge.Maleslostweight1.5foldmorethanfemales.Similarly,evenifbothgenders maintained substantially the weight loss for the first 6 months after dismissal, afterwards malestendedtogainweightfasterthanfemales.

CONCLUSIONS:Ourdatashowsuccessfulweightcontrol inadultPWSpatientsbasedonintenseandprolongedphysicalexercisewithnormaldailycalorieintake.Theapplicationoftheproposedadjuvantapproachcouldbesuitedalsotootherobesitysyndromeswithmentalretardation.

29. „noro”- onE STEP ToWardS a SuCCESSFull rEhabiliTaTion

Ioana Rotaru Rehabilitation, Treatment and Care Center “ACASA” Zalau, Romania

Key words:rehabilitation,qualityoflife,partnership.

INTRODDUCTION: „Rehabilitationisacomplexareaofactivity:medical,educational,socialandprofessionalwitchaimsentirelypossiblerestorationoffunctionalabilitylostbypatientfollowingadiseaseoratraumaandalsodevelopingcompensatorymechanisms,withaviewtoreachmaximumindividual performance andmaximumeconomic and social independence.“ (definition WHO of rehabilitation)

PRESENTATION: Talking about REHABILITATION as it is defined in the 21stCenturyEurope,forararedisease,asPrader–WilliSindrome,seemedforRomaniain2009,adream.Transitionfromthepunctiform,partialprograms,withlowperspective,towardsthoseprogramswhichreallyincreasepatient’squalityoflife,wasonlyawish.Andstill,once„ACASA”FoundationsignedthepartnershipagreementfortheProject“Norwegian–RomanianPartnershipforProgressinRareDiseases”wasshaped a hope…the hope that the final target of rehabilitation – an independent social and /or economiclifeforthepatientwithraredisease–maybeachievable.


Withinthisproject,startingwithaugust2009,inTheRehabilitation,TreatmentandCareCenter„ACASA”,werehospitalizedmonthly,groupsofpatientswithrarediseases,includingpatientswithPWS.Simultaneouslywiththepersonalizedtherapy–physiotherapyprograms,occupationaltherapy,speech therapy, diet, psychological therapy – patients and members of their family, benefited also byservicesofferedbyotherpartnersoftheproject::RomanianGeneticsSociety,MedicalUniversityTimisoara,RomanianNationalAllianceforRareDiseasesandInformationCenterforGeneticRare

Diseases:• Informationandadviceregardingthedisease;• Screeningforcomplicationsandcomorbidity;• Adviceregardingtheaccesstosocialandeducationservices;• Recreativeandsocializationactivities;

In parallelwere trained the specialists interested in rehabilitation: physicians, physiotherapistspsychologists,nurses,carriers,socialworkers.Thismodelofcollaborationbetweendifferentinstitutionsinvolvedatnationallevelinofferingmedical, social, educational services for patients with PWS, is a success. There are great benefits forpatientsandtheirfamiliesbutalsoforspecialistscommittedintreatingPWSpatients.

30. ThE naTional CEnTEr For EmPloymEnT oPPorTuniTiES For PEoPlE WiTh mulTiPlE SClEroSiS and oThEr nEurologiCal rarE diSEaSES - abiliTy aCCESS

Claudia Torjemanager de proiect, Romanian Multiple Sclerosis Society

InPraderWillidiseasemanagement,andotherrarediseases,patientsqualityoflifeisthemainpillaronwhichwe,patientorganizationsbuildouractivity.Wemeetduringthepatientslifecourse,a real need for integration in social life and especially work integration. Notice that, for the first time in Romania, through the project „The National Center for employment opportunities for people with multiple sclerosis and other neurological rare diseases - Ability Access”, financed by EuropeanStructuralFunds,we, theRomanianMultipleSclerosis Society inpartnershipwith theNationalAllianceforRareDiseasesRomaniaandthreeotherpartners,aretryingtoaccomplishinapropermannertheprocessofemploymentmediationandjobplacementforpeoplewithrarediseasesandmultiplesclerosis.

31. rarE diSEaSE CommuniTiES

Robert PletichaOnline Patient Communities Coordinator, Eurordis

ThroughastrategicpartnershipbetweentheNationalOrganizationforRareDisorders(NORD)intheUnitedStatesandtheEuropeanRareDiseasesOrganization(Eurordis)basedinParis,theprojectnamedRareDiseaseCommunitieswasborn.

RareDiseaseCommunitiesisanonlinesocialnetworkforpatientsandfamiliestoconnectwithoneandothertosupportandsharevitalexperiencesonaspectsoflivingwithararedisease.Organizedinto disease specific communities, the platform will also provide links to quality information and involvepatientassociations inthegovernanceandgrowthofeachcommunity. Aninternationalonlinepatientcommunityisanidealopportunityforpatientorganizationstoengagewithpatientswhilecollaboratingwithsimilarorganizationsonaninternationallevelinthegovernanceofthecommunity.


ProjectObjectivesinclude:• AnInternationalmeetingplaceforpatients&families• Multilingual enabled with human translation amongst all variations of five languages• Facilitatepatient&caregiversupport• Empowerpatients&caregiverstotrusttheirexperience• FacilitateprogressinresearchthroughPatientGeneratedKnowledge• Buildrelationshipsbyinvitinginterventionfrommedicalprofessionals

32. volunTEErS For rarE diSEaSES- 3 yEarS

Iulia Jurca-Simina, Florin Jurca-Simina, Ionela Moaca, Pop Norbert, Berci Stefan, Iulia Popa Mihai Gafencu, Maria Puiu volunteers in “Save the Children” organization, Timis office

„Childrenaredifferent,buthaveequalrights”-itwasthetitleofoneoftheChildRightsPromotioncampaignscarriedoutbySavetheChildrenRomaniaanditreferstohealthychildrenaswellasthosethatarenotso lucky.Mosttimes,these illchildrenarewarmandpeopleattachtothemcloserthanotherchildren.

Rarediseasesareamajorpublichealthproblemandinrecentyearstheyhavebecomeaglobalpriority in health strategies. Their rarity makes them little known by the medical staff, whichdisrupts the proper diagnosis and healthcare. In our projectswe intend to contribute, both byinvolvingasmanyvolunteersaspossibleandbyprovidinginformation,comingdirectlyintocontactwithpatientsand their families,andchange theirperceptionandevencivil societyperceptiontowardstherarediseases’issue.

Objectives. Improvingqualityoflifeforchildrenwithdisabilitiescausedbyraregeneticdiseases.Improving information quality on identification, prevention and counseling.

Methods. Activitiesbasedonspecializedvoluntary-patient-familydirectrelationshipmakinguseofplayinggames,artandgrouptherapy.

Results. Ourprojectshavestartedthreeyearsagobyformingandtrainingmedicalstudentsandyoung professionals volunteers, eager to engage both in actions to support children with rarediseasesandtheirfamiliesaswellascommunityawarenessandinformationactivitiesregardingthistopic.Weuseddifferentgamesandpuzzlestointeractwithchildren,materialspurchasedtoovercomefeelingsasembarrassmentanddisbelief,andwhichalsopromotedinteractionofchildreninordertocreatefriendshipandsupport,communicationandexperienceexchangebetweenthem.Also,wehelddrawing,modelingclay,musiccontests,duringwhichchildrenwerestimulatedtobecompetitivebutalsotohelpeachother.WiththepsychologistvolunteersfromTimisbranchofSavetheChildrenorganization,weheldmeetingswithfamiliesofchildrenwithrarediseases(supportgroups), thereby sharing their experiences in providing answers not put to questions till then,solutions forvarious situationsandmost importantly, toaccept thechildasadifferentdiseaseentity.OneofourmostimportantactivityconsistsoftheorganizationofRareDiseasesWeekinTimisoara,averydeareventtous,heldinlateFebruarysince2008.RareDiseasesDayisapublicinformationcampaignmadeinmostEuropeancountriesregardingtheexistenceofrarediseases.In Timisoara, we share information leaflets and we are available to all those who want information onrarediseases,foraweek,inLibertySquare.

Conclusions. In3yearsofactivity,sustainedactionshaveproventobeeffectivebothforchildrenwithrarediseasesandtheirfamilies,andvolunteergroupparticipants.Wehavethejoythatourefforts be appreciated by direct beneficiaries and general public positive feedback, the media andauthoritieswhichsupportus.Oursatisfactionasvolunteersismaximumwhenwereceiveasa reward a child sincere smile, and even if most are students in the final year at the Faculty of Medicine,wehopethetimewillallowasthat„voluntarysmiles”inthefuture,too.


Changing PhEnoTyPES in PradEr Willi SyndromE

Adela Chirita EmnadiUniversity of Medicine and Pharmacy “V Babes”, Timisoara

ThediagnosisofPraderWilliSindrome(PWS)isusuallyestablishedwhenobesityoccurs.Lifequalitycouldbeimprovedandcomorbiditiesreducesifearlydiagnosisandprecociousobesitymanagementis initiated along growth hormone therapy. The early phenotype in infants is associated withhypotonia,poorsuck,andfailuretothrive.Inlaterchildhood,PWSisassociatedwithintellectualdisability, hyperphagia, as well as growth and sex hormone deficiency. It is particularly important to recognize theearly phenotypeandalso the transitionbetween them, in orderestablish thediagnosisduringinfancy.Generalpractitionersandpediatriciansneedtobesensitizedtotheearlyclinicalphenotype,thedominanttraitbeinghypotonia.PWSisacomplexdiseasewithmetabolicandneurologicalimplications;itneedsacomplexapproachwithamultidisciplinaryteam,begunasearlyaspossible.

ThE groWing PaTTErn in a PaTiEnT WiTh PradEr-Willi SyndromE aFTEr gh ThEraPy

Gorduza N.C.1, Braha E.E.2, Gorduza E.V.1

1 „St. Spiridon” Hospital Iaşi, Clinic of Endocrinology, 2 Uiversity of Medicine and Pharmacy „Gr. T. Popa” Iaşi, Department of Medical [email protected]

Our study highlights the importance of growth hormone (GH) therapy in Prader-Willi syndrome(PWS).WepresentthegrowingevolutionofafemalepatientwithPWSduringtherapywithGH.Thepatientwasdiagnosedatageof31monthwithPWS.Thegirlwasbornbyhealthyunconsanguinousyoung parents, after a uncomplicated pregnancy. After birth the patient presented a severehypotonia. The GH therapy started at age of 67 months. In this moment, clinical examinationrevealed sevre obesity (+13,48 SD) macrocephaly, craniofacial dysmorphy with: short bitemporal diameter, small nose, slightly upturned palpebral fissures, small hands and feet, mental retardation (QD48),hyperphagiaandpruritus.Thehormonalstatuswasnormal.Thecytogeneticandmolecularanalysis confirmed clinical diagnosed: karyotype was normal and molecular analysis established the absenceofmetilationinpaternalgeneosSNRPN.Becausethegrowthcartilageswereopen,wedecidedtostartthetherapywithGH(Nutropin®)–0,035mg/kg/day.InmomentofbeginningofGHtherapythegrowingparameterswere:H–104cmandW–37kg.After7monthsoftreatmentthegrowthparameterswere:H–113cmandW–40kg.Thetherapystillcontinued6monthandweobtainedthefollowingparameters:H–120cmandW–45kg.Unfortunately,thetherapystoppedafter13monthsforbureaucraticreasons.Duringtheevolutionwenoticedtheabsenceofmetaboliccomplications,likediabetesmellitus.TheevolutionofourpatienttreatedwithGHwasgoodandconfirmed the necessity of application of such therapy in patients with PWS.

Posters


nEWborn WiTh hyPoTonia and diSTurbanCES oF EndoCrinE-mETaboliC FunCTionS diagnoSES WiTh PradEr-Willy SyndromE

Monica Stoian¹, Maria Puiu¹, Simona Farcas¹, Nicoleta Andreescu¹, Marioara Boia²Valerica Belengeanu¹¹Department of Medical Genetics, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania²Department of Neonatology, “Louis Turcanu” Children Hospital, University of Medicine and Pharmacy “Victor Babes”, Timisoara, [email protected]

Overlapping physical and behavioral features between syndromes are often seen, due to thephenotypiccomplexityofmanygenomicdisordersandtheir resultofdevelopmentaldelaysandbehavioral problems. Especially the neonate period of a patient is a difficult period to set an early,correctdiagnosis.Inthiscontextwedescribeamalenewborn,evaluatedforhypotoniaandcryptorchidia, later diagnosed with Prader-Willi syndrome, despite the absence feeding difficulties. The birth parameters of the premature newborn were: growth: 2100 g, length: 46 cm, cranialcircumference34cm.Theclinicalexaminationrevealed:highforehead,slightupslantingpalpebralfissures, low nasal bridge, microretrognathia and short neck. The conventional cytogenetic analysis was performed and a 46,XY normal karyotype was revealed. Reevaluated, the hormonal profile for FT3, FT4, and TSH indicated congenital hypothyroidism defined later as transitory.

Thepatientdevelopedrecurrentepisodesdebronchiolitisandpneumoniaandhypoxichypertrophiccardiomyopathy with atrial septal defect. Interesting was the metabolic profile that showed severe disturbanceswithhighlevelsofcholesterol,glycemiaandGPT.TheinvestigationofgonadotrophinssexualhormonesindicatedhighlevelsofLHandlowlevelsofFSHandtestosterone.Becauseofthehypotonia, at age of 7 months, a possible Prader-Willy syndrome was suspected and we first tested for the microdeletion, using FISH analysis with SNRPN probe, which confirmed the diagnosis. Specific genetictestingforPrader-Willisyndromeshouldbeconsideredforallneonateswithundiagnosedcentralhypotoniaevenintheabsenceoftheothermajorfeaturesofthissyndrome,becauseanearlydiagnosiswillbefollowedacorrectmanagementwithbetteroutcomeofthepatients.

PErSPECTivE daTa For CEPhalomETriC analySiS and orodEnTal PaTTErn For romanian PradEr-Willi SyndromE PaTiEnTS

Dragos Belengeanu¹, Angela Podariu², Monica Stoian³, Maria Puiu³, Dorica Dan4¹ College of Dental Technique, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania² Department of Medical Dental Prevention and Oral Health, University of Medicine and Pharmacy „Victor Babes”, Timisoara, Romania³ Department of Medical Genetics, University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania4 Romanian Prader-Willi Syndrome [email protected]

Prader-Willisyndrome(PWS)ischaracterizedbyshortstature,mildmentalretardation,hyperphagiafollowedbyobesityandfacialdysmorphy.OrofacialmanifestationsreportedinPWSincludenarrowbifrontal diameter, almond-shaped eyes with up-slanting palpebral fissures, thin vermilion border and a triangular mouth. Descriptions of intraoral and dental features are rare and are mostlylimited to case reports. Oral findings include the presence of hypoplastic enamel, low basal salivary secretion,delayedtootheruptionandexcessivetoothwear.Thestudyispartofthedoctoralthesesandwillalsofollowapossiblecorrelationbetweentheetiologicheterogeneityofthesyndromeand


cephalometricparameters.Weelaboratedanevaluationdiagnosisalgorithmthatwillbeappliedtoallpatientsthatwillbeenrolledinthestudy.Theauthorstetsasmaingoalforthisstudytoevaluatecraniofacialparameters,craniofacialgrowthandorodentalmanifestationsofRomanianpatientswithPrader-Willisyndrome.Atthesametimewewillassesstheorodentalmanifestationsrelated to salivary flow and biochemical composition of the saliva. Within the study group we intend to evaluate the implications of specific dietary and/or growth hormone therapy upon the priormentionedaspectsversusforthepatientswhodidnotfollowupregimesorgrowthhormonetherapy.ThefollowupdataofthepatientswithPWSareessentialforthedevelopmentofguidelinesforstomatologicaltreatment.

digESTivE diSordErS in PradEr Willi SyndromE

Maria Pop, Maria PuiuUniversity of Medicine and Pharmacy „V. Babes”, Timisoara

Prader–Willisyndrome(PWS)isaneurobehavioraldisordercausedbythelossofmultiple,paternally-expressed, imprinted genes on human chromosome 15q11-q13.Also, PWS is the most commongenetic causeofobesityand theobesity inPWS is theconsequenceof severehyperphagiaanddecreased overall metabolism. Recent progress in the field of energy homeostasis was triggered bythediscoveryofadipocytehormoneleptinandrevealedacomplexregulatoryneuroendocrinenetwork.

Theanimalresearch,inrecentyears,explainsthedigestivedisordersinPWS.Understandinghowthestomachisincludedinthefunctionalendocrinerelationship(growthhormone,hormoneghrelin,etc.)couldexplainthe implicationsforthetreatmentandforavoidingcomplications.DigestivedisordersinPWShaveagreatimpactonmorbidityofthesepatients.

EmoTional and bEhavioural ProblEmS in PradEr Willi SyndromE

Catana Andreea, Dronca Eleonora, Serban Simona, Miclea Diana, Pop Ionut, Felicia Petrisor, Pop I. VictorUniversity of Medicine and Pharmacy, Cluj-Napoca, Romania

Key words:obsessivecompulsivemaladaptivebehavior,cognitivedisabilities,

PWSisacomplexgeneticdisorderthattypicallycauseslowmuscletone,shortstature,incompletesexualdevelopment,cognitivedisabilities,problembehaviors,andachronicfeelingofhungerthatcanleadtoexcessiveeatingandlife-threateningobesity.Althoughconsidereda„rare“disorder,Prader-Willisyndromeisoneofthemostcommonconditionsseeningeneticsclinicsandisthemostcommon genetic cause of obesity that has been identified. PWS is found in people of both sexes andallraces.

People with PWS have a flaw in the hypothalamus part of their brain, which normally registers feelingsofhungerandsatiety.Whiletheproblemisnotyetfullyunderstood,itisapparentthatpeople with this flaw never feel full; they have a continuous urge to eat that they cannot learn to control.Inadditiontotheirinvoluntaryfocusonfood,peoplewithPWStendtohaveobsessive/compulsivebehaviorsthatarenotrelatedtofood,suchasrepetitivethoughtsandverbalizations,collectingandhoardingofpossessions,pickingatskin irritations,andastrongneedforroutineandpredictability.FrustrationorchangesinplanscaneasilysetoffalossofemotionalcontrolinsomeonewithPWS,rangingfromtearstotempertantrumstophysicalaggression.


ThE imPaCT oF ThE diagnoSiS and diSabiliTy on ThE Family and PErSon WiTh PradEr-Willi SyndromE

Dronca Eleonora, Catana Andreea, Serban Simona, Miclea Diana, Pop Ionut, Pop I Victor

Key words:chalenging,patients,parents

Araregeneticdisorderistobeconsideredalifelongcontinuumchallengesforchildrenandadults.Prader-Willisyndrome(PWS)isageneticconditioncausedbytheabsenceofchromosomalmaterialfromchromosome15.ThegeneticbasisofPWSiscomplex.Characteristicsofthesyndromeincludedevelopmental delay, poor muscle tone, short stature, small hands and feet, incomplete sexualdevelopment, and unique facial features. Insatiable appetite is a classic feature of PWS. Thisuncontrollableappetitecanleadtohealthproblemsandbehaviordisturbances.DiagnosisussulalyhasabigimpactofthefamilyofapersonwithPraderWilliSyndrome.Batllelingtheoutcomingsymptomscanbechalengingnotonlyforthepatient,butalsoforparents,siblings,friendsandacquintances.

hEalTh iSSuES and ConCErnS in PradEr Willi SyndromE

SerbanSimona,CatanaAndreea,DroncaEleonora,MicleaDiana,PopIonut,PopIVictorUniversityofMedicineandPharmacy,Cluj-Napoca,Romania

Keywords:obesity,behaviour,developmentalconcerns

Prader-Willi syndrome is a complex genetic condition that affects many parts of the body.It is characterized by excessive hunger, known as hyperphagia, mental retardation, as well asseveral other physical symptoms.There are a number of concerns associated with Prader-WilliSyndrome (PWS).These concerns are related to areas such asweight, behavior, developmentalconcerns, and additional concerns. What follows are descriptions of some of these concerns.

a FEW WayS To managE bEhavioral diSTurbanCES in PradEr Willi SyndromE

Mariana CojocaruPhD Student, “Carol Davila” Univ Med Pharm, Bucharest – Romania

Prader Willi Syndrome (PWS) is a neurogenetic disorder with a specific behavioral phenotype. Typical behavioral disturbances include: excessive interest in food, skin picking, difficulty with change in routine, mood fluctuations, temper tantrums, violent outbursts, obsessive/compulsive behavior; tendencytobeargumentative,oppositional,rigid,manipulative,possessive,andstubborn;morethanthat,thepeoplewiththisconditionareperseverating,stealingorlying.Thispaperhighlightstheroleofmultidisciplinaryapproachtomanagementandtreatmentofthesyndrome.Managementof behavioral problems is more effective if detected early as these difficulties may increase with age.DuetotherangeofproblemsandvariabilityofsymptomseverityacrossindividualswithPWS,managementofPWSisage-dependent,multidisciplinary,andutilizesaproblembasedapproachtocatertoeachindividual.Nowadays,thereisnocureforPWS.Allthatcanbedoneistomanagethehealthproblemsthesechildrenareinclinedtodevelop.EarlydiagnosisandinterventionscanhelpindividualswithPWStoliveamuchmorecomfortableandhealthfullife.Basedonmedicaland psychological evaluations, medication and individual education plan should be initiated asearlyaspossible.Physicalandoccupationaltherapyalongwiththespeechtherapymayboostandsupportmotor development andhelpwith speech setbacks. Parents andother familymembersneed emotional, financial and informational support.


C-FliP rEgulaTion oF EndoThElial CEllS aPoPToSiS in ThromboTiC ThromboCyToPEniC PurPura (TTP) – liKE CondiTionS

Jeffrey Laurence1, and Radu Stefanescu2,3

1 Department of Medicine, Division of Hematology-Oncology, Weill Medical College–Cornell University, New York, NY; 2 Titu Maiorescu School of Medicine, Bucharest, Romania; 3 GeneXplore, Romania

Thromboticthrombocytopenicpurpura(TTP)isararedisease,withanestimatedincidenceof2–10casespermillion/yearinallracialgroups.Animportantfactorinthepathogenesisofthromboticthrombocytopenicpurpura(TTP)isinjurytomicrovascularendothelialcells(MVECs)andwehavedemonstratedthatapoptosisofMVECscanbeinducedinvitrobyplasmaobtainedfromTTPpatients.1WehavealsoobservedthatMVECsderivedfromthebrain,kidneys,andskinaremostsensitivetoTTPplasma,whereasthosederivedfromlungandliverarenot.1

Microvascular endothelial cell (MVEC) injury coupled to progression of platelet microthrombifacilitated by ADAMTS13 deficiency is characteristic of idiopathic and HIV-linked thrombotic thrombocytopenicpurpura(TTP).2Cytokinescapableof inducingMVECapoptosis invitro,tumornecrosis factor–related apoptosis-inducing ligand (TRAIL) and interferon (IFN)–γ are up-regulated inbothTTPandHIVinfection.Clinicallyrelevantlevelsofthesecytokinesactinsynergytoinduceapoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary MVECs.2 Thisreflects the tissue distribution of TTP lesions in vivo. The process appears to involve cooperation between IFN-γ and TRAIL in suppressing, via posttranscriptional mechanisms, a caspase-8regulatorcellularFLICE-likeinhibitoryprotein(c-FLIP)cytoprotectivepathwaybyenhancedubiquitinationofthec-FLIP,targetingitforproteasomedegradation.

WeusedMVECsderivedfromtheskinasrepresentativeofthesensitivegroupandMVECsderivedfromthelungasrepresentativeofthenonsensitivegroup.c-FLIPsilencingwithanti-FLIPshortinterferingRNA(siRNA)inpulmonaryMVECsrenderedthemsusceptibletoTTPplasma-andcytokine-mediatedapoptosis,whileup-regulationofc-FLIPbygenetransferpartiallyprotecteddermalMVECs fromsuch injury.TTPplasma–mediatedapoptosisappears to involvecytokine-inducedaccelerationofc-FLIPdegradation,sensitizingcellstoTRAIL-mediatedcaspase-8activationandcelldeath.

Thediscoveryoftheroleofc-FLIPinregulationofMVECapoptosismayhaveimportanttherapeuticimplications for TTP. The possibility that specific modulation of TRAIL or, more generally, manipulation ofc-FLIP–relatedpathwayscouldblockprogressionofECinjurycharacteristicofatleastsubsetsofpatientswithTTPisimportanttobefurtherstudied.

1. Mitra D, Jaffe EA, Weksler B, Hajjar KA, Soderland C, Laurence J. Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells. Blood. 1997;89:1224–1234.2. Stefanescu R, Bassett D, Modarresi R, Santiago F, Fakruddin M, Laurence J. Synergistic interactions between interferon-gamma and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma-associated apoptosis.Blood. 2008;112(2):340-9


lobar holoProSEnCEPhaly-a rarE diSEaSE

Marioara Boia1, E.S. Boia*, Maria Puiu**, Dana Iacob*, Aniko Manea*University of Medicine and Pharmacy ”Victor Babes”, Timisoara, Romania

Keywords:holoprosencenphaly,echography,newborn

Introduction:Holoprosencephalyappearsbetweenthe4-thto8-thweekofpregnancyduetothelackofcleavageoftheprosencephalusinthetelencephalusanddiencephalus.Theattendanceis1at10.000livenewborn,factsthatprovesthatitisararedisease.Itis60timeshigheratabortedhumanembryos.Dependingonthedegreeofdifferentiationandseveritywecanhave3subtypesofholoprosencephaly:alobar,semilobarandlobar.Material and Method: The authors present a study of 3 premature newborns, with lobarholoprosencephaly,anextremelyrareaffectioninthecurrentmedicalpractice.Twoofthepatientsdidn’tshowanysymptomsuntiltheageoftwoweekswhentheypresentedgeneralizedtonic-clonicseizures.Oneof thenewborns showedotherassociatedmalformations:unilateralanophthalmiaandcongenitalseptaldefect.Cerebrallesionswerehighlightedbycerebralimagingmethods–headultrasonography, CT in one of the cases and MRI in 2 cases. Those investigations showed specific lesionsatthemedianline.Thekaryotypewasnormalin2ofthecases;oneofthecasespresentedtrisomy13.Theevolutionofthecaseswassevere,causingdeathinoneofthecasesandslowlyevolutingwithrecurrentseizuresandmotor-andpsychicretardationintwoofthecases.Conclusions: Lobar holoprosencephaly is a rare affection, without specific clinical expression and itsdiagnosiscanbeeasilymissedintheneonatalperiod.Cerebralimagingwastheprimarymethodinthesettingofthediagnosis:headultrasonographytrackeddownthelesions,whileCTandMRIestablishedtheirextension.

EFFECTivE rEhabiliTaTion TrEaTmEnT in a CaSE WiTh doublE ChromoSomal dElETion

Dorina STOICANESCU1, Mariana CEVEI2 1University of Medicine and Pharmacy „Victor Babes”, Department of Medical Genetics, Timisoara, Romania2University of Oradea, Faculty of Medicine and Pharmacy, Medical Rehabilitation Clinical Hospital Felix Spa, Oradea, Romania

Congenital anomalies represent one of the prioritary problems in pathology. It is estimatedthat about 12-25% of anomalies have genetic causes. Of these, the majority are chromosomalanomalies.Chromosomaldeletionsareusuallycharacterizedbycraniofacialdysmorphism,differentphysicalabnormalitiesandmental retardation.Deletionofthe longarmofchromosome18 isarare chromosomaldisorderwithaphenotype thatmayvary considerably in rangeand severity,dependingon the typeofdeletionand locationof thebreakpoint. Subjectshavecharacteristicfeatures including short stature, mental retardation, hypotonia, craniofacial abnormalities andneurologic deficiencies with a high incidence of dysmyelination. We report the case of an infant withmultiplecongenitalabnormalities,craniofacialdysmorphism,severementalretardationandseverehypotonia,whowasfoundtohavedeletionsofthelongarmofchromosomes13and18.Shewasincludedinarehabilitationprogramfromtheageofelevenmonths.Theobjectiveswereto prevent muscle atrophy, improve muscle tone, maintain joint mobility and stimulating thedevelopmentofmotorskills.Weobservedthecaseforaperiodofoneyear,periodicmonitoringofmuscle tone and performance, along with the neurological status, showing significant motor and mentalimprovement.Rehabilitationtreatmentwaseffectiveandmustbeanearlyintervention.Assessment of cases with hypotonia is best accomplished by a multidisciplinary team includingpediatricians,medicalgeneticists,neurologistsandphysicaloroccupationaltherapists.


oral maniFESTaTionS inCluding gingival FibromaToSiS in rarE diSEaSES

Talpoş Ş, Puiu M, Talpoş C, Popa MUniversity of Medicine and Pharmacy “Victor Babeş” Timişoara, RomaniaFaculty of Dental MedicineDepartment of Oral and Maxillo-Facial SurgeryDepartment of Medical Genetics

Generalised gingival enlargement may occur as a result of local inflammation, hormonal dysfunctions, leukemiaorasaresponseofvariousmedications(phenitoin,diltiazem,nifedipineetc.).Forthesyndromesdiagnosis,theoralexamwasoftenindispensableandhighlyimportant,revealingraredetectablediseases.

Gingival fibromatosis with hypertrichosis is the most common of the syndromes, but it still appears in other syndromes like Murray-Puretic-Drescher syndrome, Rutherfurd syndrome, Laband andZimmerman-Labandsyndrome,Jonessyndrome,Ramonsyndromeandothers.Historyandphysicalexamination will serve to distinguish these disorders from gingival fibromatosis.The Department of Genetic from ,,Louis Ţurcanu” Children’s Emergency Hospital, between 2005 to2009investigated470childrenwithdifferentgeneticdiseases.Therewereseveral idiopathicgingival fibromatosis cases (12%) where the interdisciplinary approach was mandatory to establish thediagnostic.

The most common reported syndrome with gingival fibromatosis is hypertrichosis, epilepsy and mentalretardation.

The clinical implications of the gingival fibromatosis, with genetically controlled patterns, are importantinestablishmentofearlydiagnosisandinappropriatetreatment.Key words: gingival fibromatosis, rare diseases, interdisciplinary approach.

CliniCa and biologiCal ConFirmaTionin an SuSPiCion oF gluT1 dEFiCiEnCy SyndromE

DumitriuSimonaUniversity of Medicine and Pharmacy “Victor Babeş” Timişoara, Romania

Themedicalandthelifestoryofan5yearsoldboywitchhadbeenwroutteonlytogethersincehewas2yearsarethebestexampleofagoodcomunicationbetweenfamilyandspecialists.Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized by infantile seizures refractory to anticonvulsants, followed by deceleration of head growth, delays in mental andmotordevelopment, spasticity, ataxia, dysarthria, opsoclonus, andotherparoxysmalneurologicphenomena,oftenoccurringpriortomeals.

Andrei was considered a normal baby at birth. Birth weight and Apgar scores were normal. His first seizureoccurredatage3,describedasmyoclonicjerkingofshouldersandarms,noddingofthehead,rollingoftheeyes,hypotonia,andimpairedconsciousness.Frequentdailyseizuresoccurredpredominantlyearlyinthemorning.HewasevaluatedforLennoxGastauxsyndromeandreceiveddifferent AED in polytherrapy and ACTH with no clinical benefit. His developement was delayed especialyinlanguageandmotorcoordination.Monitoringhisstateweobservedapatternoftheseizures:earlyinthemorningfollowedbyalongsleepduringthedayandprecededbycompleteinsomnia1-2nightsbefore.Ataxia,continnousmyoclonicseizures,aphasy,confusionwereaddedinafewhours.

MRIshowedonlyamoderatefrontalatrophy.EEGinthefastingstatedemonstratedmildtomoderateslowingofbackgroundactivityandmultifocalandgeneralizedhigh-amplitudeirregularspikesand


spike-and-waves,mostof thesedischargeswere inclinically silent,onlyoccasionally theywereaccompaniedbymyoclonicjerksofshouldersandarmsornoddingofthehead.EEGrecording1hafterbreakfastshoweddisappearanceormarkedreductionofepilepticactivity.CSF glucose values were decreased to 33 mg/dl whereas hisr blood glucose values, measuredsimultaneously,werenormal(84 mg/dl).TheresultingCSF/bloodglucoseratiowasreducedto0.33(normal,∼ 0.65).TheseuptakevaluesaretypicalforpatientswithGlut1-DS.

Initiationofketogenicdiet(KD)ledtodramaticimprovementwithregardtoepilepsyaswellasmotor and cognitive capacities.The children show recurring seizureswith nodding of theheadandmarkedepileptiformdischargesinEEGifascheduledketogenicmealisdelayed;stilltheyareparticularlysusceptibletoseizuresinthemorningbeforebreakfast.

Specific investigations confirming Glut-1DS definitely, such as erythrocyte glucose uptake studies andmutationanalysisofGLUT-1,aretimeconsumingandexpensive.

Basedonthemotherobservations,weperformedandpre-andpostprandialEEGrecordingsinaboywithseizuresaggravatedbyfastingandamelioratedbyGlucoseivadministartion.ThissimpleexaminationprovidesapowerfultooltoidentifypatientswithprobableGlut-1DS.

From a ParTiCular PhEnoTyPE To a rarE gEnETiC diSEaSE – a PEdiaTriC aPProaCh

T.Marcovici1,2, I.Simedrea1,2, G.Brad2, L.Olariu1,2, M.Puiu1,2

1 “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania2 “Louis Turcanu” Children’s Emergency Hospital, Timisoara, [email protected]

Dismorphologydiagnosisrequiresamultidisciplinaryapproach,withadirectinputofpediatricians.Theevaluationofchildrenwithprimaryabnormalitiesofdevelopmentisgradualanditincludestheir complete history, physical examination, laboratory investigations and genetic counseling.The identification of a rare genetic disease with somatic and / or cognitive imprint requires the collaborations of general practitioners and pediatricians. The identification of a primary abnormality of development often leads to the detection of one or more, major or minor malformations,respectively.Birthrateofminoranomalytothemajoroneis5:1.Theclinicalevaluationsduringontogenesisfrequentidentifythepresenceofplurimalformativesyndromesorraregeneticdiseases.The aesthetic anomalies are easy to identify, while visceral malformations often require high-performanceimagingandinterdisciplinaryexamination.Sensorydysfunctionsasacharacteristicofraregeneticdiseasesarediagnosedsometimeslate. Inthesecases,thefunctionalconsequencesaremajor,withsevereimpactonchildandhisfamily,especiallyonthelifequality.The recognitionof structural variants without pathological significance involves a rigorous clinical evaluation of the children.Documentationofpossibleconsequencesoftheprimaryabnormalitiesofdevelopment,early or late diagnosed must represent a constant concern of all pediatricians. Conclusions:Early identification of the phenotypic characteristics is the background of an active and accurate diagnosis,prognosisandgeneticcounseling.Thecomplexteammanagementoftheraregeneticdiseases benefit in our country from the direct involvement of many dedicated pediatricians.


gEnETiC CounSElorS and PrEdiCTivE mEdiCinE: a nEEdEd ProFESSion in romania

Maria Puiu1, Adela Chiriţă1, Dorica Dan21 “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania2 Romanian Prader Willli Association

Genetic counseling isaprofessionappeared thatappearedearly in theU.S.andmore recentlyinEurope. Theseprofessionalsneedtoacquireadiverseknowledgetobecomecompetent,forexample,toestablishrelationshipsandtoclarifythepatient’sconcernsandhisexpectations,tomakeappropriateandaccurateassessmentofgeneticrisk,toworkwithamultidisciplinaryteamofhealth,tointegrateethics,medicalandlegalissues,touseinformationsystems,andcontributeto research andeducation.Theprofession is becomingmore andmorenecessary in addressinggeneticpathology.TheEuropeanNetworkofGeneticNurses(alsootheritemswhichdonotexistinRomania)andgeneticcounselors,alongwiththeESHGandotherspecializedforumsparticipateintheeducationalsettingprofessionalstandardsforgeneticcounselorsinEurope.Wehopethesetools will convince the authorities in Romania to approve this profession, for the benefit of our patientswithrarediseases.

aSESSmEnT oF mulTiPlE malFormaTion in nEWborn. CaSE rEPorT.

Belei Oana, Giurescu Ramona, Micle Ioana, Pop Elena, Marazan Monica, Simedrea Ioan, Puiu MariaFirst Pediatric Clinic, UMF Victor Babes Timisoara

Theauthorsreportthecaseofapretermbabyaged6daysold,presentingmultiplemalformations,thatwasframedintoNoonansyndrome.

ThetermNoonansyndromeisappliedtophenotypicmalesandfemaleswhohavecertainanomaliesthatoccurealsoinfemaleswithTurnersyndrome.Theseboysandgirlshavenormalkaryotypes.The disorder is usually sporadic, but affected siblings of the same or different genders havebeenreported.Totalorpartialexpressionispresentin20%ofrelatives.Reportsofmaletomailtransmissionsuggestanautosomaldominantgenewithvariableexpressivity.Thegenehasbeenmappedonchromosome12q.Themostcommonabnormalitiesareshortstature,webbingoftheneck, pectus carinatum or pectus excavatum, cubitum valgum, congenital heart diseases andcharacteristicface.Hypertelorism,epicanthus,antimongoloidpalpebralslent,micrognathiaandearabnormalitiesarecommon.Malesfrecquentlyhavecryptorchidismandsmalltests;thaymaybehypogonadalornormal.Pubertyisdelayed2yearsonaverageandadulthightusuallyreachesthelowestlimitofthenormalpopulation.

Thecasepresentedisa6daysoldmalenewborn,bornatthegestationalageof36months,thatwasadmittedfortheevaluationofmultiplemalformations.Uponadmittance,theinfantpresentedalteration of health status, jaundice, trophy disturbances, dysmorphic facies, antimongoloidpalpebralslant,hypertelorism,micrognathia,webbingoftheneck,earslowset,quadraticpalms,simian crease.The patient presented tachipneea, diminished breath sounds on right inferiorpulmonaryarea,tachycardiaandgradeIIIrdsystolicmurmur.Theneonatepresentedalsoposteriorhypospadias,bilateralcryptorchidism,andwasveryspastic.Unfortunately,theneonatediedattheageof20daysduetoasevereneonatalinfection.Thepathologicalexaminationhasshown:disseminatesintravascularcoagulation,hemorrhageofcerebralarteries,hypoplasiaoftherightinferiorpulmonarylobe,congenitalrightherniaofthediaphragm,pulmonaryarterystenosis,atrialandsuperiorventricularseptaldefect,leftcongenitalmegaureterandcongenitalmegacolon.The particularity of the case is the association of Noonan syndrome with unusually anomalies:megaureter,megacolonandthecongenitalrightherniawiththeliverpassingthroughthediaphragm.Thiscomorbidityhasdeterminatehisdramaticallyevolution.


a rarE CaSE oF hEPaTomEgaly

MariaPop1,2,I.Plesea2,B.Farcasescu2,M.Serban1,2

1„VictorBabes”UniversityofMedicineandPharmacyTimisoara2.„LouisTurcanu”EmergencyChildrenHospital–IIIrdPediatricClinic

Introduction. Glycogen storage diseases (GSD, glycogenosis) are inherited metabolic disorders,characterizedbytheexcessiveaccumulationofglycogeninoneormanyorgansortissues,duetotheabsence or deficiency of one of the enzymes responsible for making or breaking down glycogen.

Aim:presentingaparticularcaseoftypeIXglycogenosis

Material and method:malepatient,1yearand6monthsold,addressedtoourClinicforabdominalenlargement. A complete evaluation was necessary because of the complexity of the case :biological andmetabolic investigations, enzymatic tests, genetic tests,paraclinic investigationsandmultidisciplinaryconsults.

Results and discussions:Clinical features:patienthistoryrevealedmorninghungerandtheclinicalexamshowedaparticularphenotypewith smallheight forage,“doll face”,enlargementof theabdomen,hepatomegaly,normalmuscletone.Biological investigations:hypoglycemia (59 – 60mg/ml), importanthepatic cytolysis (120 –380UI/l).Abdominal ultrasonography confirmed the hepatomegaly (left hepatic lobe – 6 cm, right hepatic lobe–12cm).Theenzymatictestsrevealedaphosphorylasebkinase deficiency in leukocytes and erythrocytes, andthegenetictestsshowedaPKHA2gene1-pbdeletiononchromosomeX.Diagnosis:basedontheclinicalfeaturesandinvestigationswehavereachedthediagnosisGlycogen storage disease type IX α2.

Conclusions: type IX α2 glycogenosis only affects the liver (in comparison to type IX α1 glycogenosis whichalsoaffectsthemuscles)anditisanX-linkedinheriteddisease(womenarecarriersofthedefectivegeneand50%oftheirmalechildrenwillinheritthedisease).

a nEW CaSE 46,xx malE SyndromE

Cristina Gug1,2

1 Genetics Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania 2 Cabinet Medical de Genetica ”Dr. Cristina Gug”, Timisoara, Romania

The46,XXmalesyndrome(delaChapellesyndrome)isararelyseengeneticdisordercausingmaleinfertility.ItisgenerallyaresultofunequalcrossingoverbetweenXandYchromosomesduringmeiosis.

Case report:A32yearoldmalewasreferredtousforcytogeneticanalysisfromtheinfertility.Chromosomal analysis showed 46,XX karyotype and molecular studies showed the presence oftheSRYgene.Hehadnormalexternalmalegenitalphenotypeandsecondarysexcharacters.Nogynecomastiawasnoted.Atphysicalexaminationsoftandatrophictesteswerepalpated.Semenanalysis confirming azoospermia. The gonadotrophins were elevated. There was no family history ofsexreversal.Therapyisbasedonandrogenreplacementtherapy. Intheliterature,therearevariousphenotypicpropertiesof46XXmalepatients.


rarE CauSE oF hEmoPhagoCyTiC diSordEr - ChEdiaK-higaShi SyndromE-CaSE rEPorT

E. Boeriu 1,2, M. Cucuruz1,2, M. Lelik1,2, G. Brad1,2, I. Ursache1,2, A. Botiz1, M.Puiu, M. Serban1,2

1 Children’s Emergency Hospital „Louis Turcanu, Timisoara 2 3rd Pediatric Clinics, Hemato-Oncology Department, University of Medicine and Pharmacy „V. Babes „Timisoara

Chediak-Higashi syndrome, diagnosed and followed by us, was defined by the presence of oculocutaneousalbinism(hair,skin,eyes),thecommonbacterialinfectionsassociated,thepresenceofpositiveazurophillicperoxidasegranularfoundintheleukocytesfromtheperipheralbloodandbonemarrowandpositivefamilyhistory.

Our diagnosis consisted in the identifications of the typical clinical, biological, immunological and evolutionaryfeaturesofthisdisorder.

Clinical, we identified the typical symptoms characteristic for severe Chediak-Higashi syndrome (significant visceromegaly, early appearance of immunodeficiency syndrome manifested as abscesses, impairedofcentralnervoussystem).

Biological events can be assessed as moderate (triglycerides = 2.45-3mmol/L, fibrinogen=1.19-1.65g/L,ferritin=341-490ng/ml).

The macrophage activation syndrome found in the bone marrow and manifested as severecitophagepathologicalaspectswasresponsibleforthepresenceofseveretricitopenia. Intheseconditions, immunological,wenotedasatisfactoryhumoral immunesystem.ThelymphocytesBremainedconstantover1500/mm3,whiletheserumIglevelswerenormalorevenhigherthanthenormal values (IgG = 15.06 to 18.5 g / L). NK cells CD3-CD16 + CD56 + were within normal limits, sometimes slightly increased (689-822/mm3).Thecasehadanunfavorableevolutionunder thetreatment according to “TreatmentProtocol of the Second International StudyHemophagocyticLimphohistiocytosis2004”.

In conclusion,wenoted thecomplexityanddiversityof theconstitutional repercussionsof thephagocytic deficiencies responsible for macrophage activation. It involves complex disorder in macrophagesystem/immune.

PalliaTivE mEdiCinE in rarE diSEaSES - inTErFErEnCE and ChallEngES

E. BOERIU 1,2, M. CUCURUZ 1,2, S. ARGHIRESCU 1,2, R. COSTEA 1, G. BRAD 1, I. URSACHE1, M. SERBAN 1,2

1 Children’s Emergency Hospital “Louis Turcanu”, Timisoara2 III Pediatric Clinic, Department Of Hematology-oncologyUniversity Of Medicine And Pharmacy “Victor Babes” Timisoara

Introduction:Althoughrare,oncologicaldiseasesareanimportantpathologywithunfavorableandprogressive evolution. This fact justifies the implementation of the principles of palliative medicine inoncologyandbonemarrowtransplantationclinicalpractice.

Objectives:WeaimedtoanalyzethecaseswithunfavorableevolutionadmittedtothePediatricOncologyandBoneMarrowTransplantDepartmentof„LouisTurcanu”ChildrenHospitalTimisoarabetween2008-2010and tohighlight the roleofpalliative caremeasures in childrenoncology .

Materials and methods:Thestudygroupconsistedof50patientswithagebetween1monthto31years(51.6%girlsandboys48.4%).31patientswerefromtheOncologyDepartmentand19casesofBoneMarrowTransplantDepartmentwithunfavorableevolutiontodeaththatcamefromTimis


andthesurroundingcounties.Thestudylotwasanalyzedintermsofclinical,laboratory,causeofdeath,theevolutionofsymptomsandtheircontrol.Wepracticedthestatisticalanalysisofdata.

Results: Acute lymphoblastic leukemiawaspresent in28.5%ofcases, followedbybraintumors(25.8%)andsarcomas(19.35%).Theintervalfromtheonsetofmalignancytodeathwasin51.6%ofcasesbetween1-3yearsandin16.2%ofpatientsoverthreeyears,whilelessthan3monthswasobservedin16.2%persons.Curativetherapywasfollowedbypalliativecarein74.19%casesand6.45%ofpatientsreceivedjustpalliativecare.Outof97patientsfromBoneMarrowTransplantDepartment, 19 (19, 58%) had unfavorable evolution towards death: 12 cases with progressivedisease,5caseswithsepsis,1casewithbronchopneumoniaandasinglecasewithgraft-versus-hostdisease.Thepainwaspresentinallcases,controlledwithmorphineexcepttheneuropathicone.

Conclusion:Palliativemedicineissituatedattheinterferenceofseveralmedicaldisciplinesanditaddresses theend-stagepatients to improvequalityof lifeuntil themomentofdeath.Shortperiodbetweendiagnosis anddeathexplains theapplicationofpalliativemedicine, evenafterthediagnosisofmalignancy.Thepainwasthemostcommonsymptom,whichwaswellcontrolled,exceptforneuropathicpain.ItisveryimportanttocontrolthesymptomsinPediatricOncologyinordertoimprovethequalityoflifeofthesepatients.

Primary immunodEFiCiEnCiES - CurrEnT diagnoSiS and managEmEnT

Maria Cucuruz1, Estera Boeriu1, Mihaela Bătăneanţ1, Giorgiana Brad1, Maria Puiu2

1 III Pediatric Clinic, University of Medicine and Pharmacy „Victor Babes” Timisoara; 2 Discipline of Genetics University of Medicine and Pharmacy „Victor Babes” Timisoara

Primary immunodeficiencies (PIDs) are genetic diseases defined by intrinsic defects of the immune system.Ifafewyearsago,PIDswereconsideredrarediseases,theirprevalenceiscurrentlyestimatedat1/300people.Earlydiagnosisisextremelyimportanttopreventinevitablecomplications,life-threateningdiseasesuchassevereinfections,autoimmunediseases,malignancies.Expertsindicatethe following diagnostic stages: possible, probable and definitive diagnosis.Currently, the diagnostic target is the genetic diagnosis, which provides the definitive diagnosis. In thiscontext,theauthorsexemplifysomecasesofPIDssuchascongenitalagammaglobulinemia,CVID(Common Variable Immunodeficiency), ataxia-telangiectasia, chronic granulomatosis disease. Also, they presented the defined stages of diagnosis. Unfortunately, most cases remain in the possible / probable phase of diagnostic based on more or less efficient immunological investigations. In recent years, there were described some forms of genetic diagnosis of PID, which made the definitive diagnosisofdisease.Wehope inthefuturethe increasingrangeofgeneticdiagnostics inmanyformsofPIDs.

ThE nEonaTal SCrEEning For CongEniTal hyPoThyroidiSm in TimiS arEa – 10 yEarES oF ExPEriEnCE

Otilia Marginean1, Ioan Simedrea1, Ioana Micle1, Marilena Lesovici1,Olaru Gabriela2

Ilie Constantin3, Maria Puiu1, Roxana Gruescu1, Elena Jivet1 , Tira Maria1 1 Clinical Children Hospital „ Louis Turcanu” Timisoara2 „Marin pPopescu ” Maternity of Timisoara3 Bega Maternity of Timisoara

AIM:Toassessthenationalprogrameofneo-natalscreeningafter10yearsofworking.MATERIAL AND METHODS :Between1.12.1999 -31.12.2009wehave towgroups:A)newbornbabies,fromTimisoarabetween1.01.2001-31.12.2003,andB)newbornsfromTimisregionalhospital


(Lugoj,Jimbolia,SannicolauMare,Deta,Faget)between01.01.2004-31.12.2010.WeanalisedTSHinperipherealbloodof4-day-oldbabiesbyDelphiaMethod(2001-2006)andbyElisamethodfrom2007. The TSH value more then 20 μg/dl were considered suspect for hypothiroidism end then the childwerereexaminedbythepediatricendocrinologist.

RESULTS AND DISCUSSIONS: Were analysednewbornsspotbloodseamplesfrommaternity.AftertheextiendedanalisesoftheholeTimisareawetestedmorenewbabiesbornsbutwehavealotofadministrativ problems. Monthly analysis both in the first and in the second pediod showed that an importantnumberofnewbornbabieshadnotbeenincludedinthescreening. 8patients confirmed by the pediatric endocrinolog, under substitutive treatment have normal development withoutneurologicproblens.587patientswithtransitoryhighlevelsofTSH,hasbeenexcludedfromthisstudy.TheinitialpriceforTSHanalisewere10,5Ronandinthismonentis6,5Ron.

CONCLUSIONS: 1. The neonatal screening is important and benefical2. Without treatment from the first days of life the neurological damages are extremely severe

andirreversible.3.Thenumbersofsamplingandthepriceoftheanalisecanbeinprouve.


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