P1909Linkage of multigeneration families afflicted with psoriasis in the New-foundland and Labrador Founder population

Wayne Gulliver, Faculty of Medicine, Memorial University of Newfoundland, St.John’s, Newfoundland, Canada; Catherine Street, Faculty of Medicine, MemorialUniversity of Newfoundland, St. John’s, Newfoundland, Canada; K. Adam Baker,NewLab Life Sciences, St. John’s, Newfoundland, Canada; Proton Rahman, Facultyof Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland,Canada

Background: The Newfoundland and Labrador founder population is invaluable fordiscovering the underlying genetic cause of human diseases. Several inflammatorydiseases, including psoriasis, are more common in the province than other regionsof the country. Althoughmany common genes associated with psoriasis have alreadybeen uncovered, it is believed that many rare genes have yet to be discovered. As afirst step, a linkage of multigenerational families with psoriasis is being performed.

Methods: Family information and DNA was collected for 21001 subjects in a studywhich investigated the genetics of psoriasis within the province and uncoveredHLA-Cw6 as a susceptibility gene. At that time individual family pedigrees wereproduced by hand. Since then, the Population Therapeutics Research Group (PTRG)has been created within the Faculty of Medicine at Memorial University that can linkfamily information to the Newfoundland Genealogy Database to produce largepedigrees to determine the relatedness of subjects. Ten large families with six ormore psoriatic family members have been identified for linkage.

Results: The 10 identified families have a linkage of disequilibrium (LOD) score$ 2.3, with two families having a LOD[3.0 ideal for performing a genome wideassociation scan. The mean (6 SD) of affected family members is 7 (61). The resultsof the pedigree analysis will be presented at the meeting.

Conclusion: Pedigree analyses in the Newfoundland founder population haveproven invaluable for the planning of studies to determine the genetic cause ofdiseases. This is an important first step in the planning of a genome wide associationstudy to uncover novel, less frequent genes conferring susceptibility to psoriasis.

FEBRUARY

cial support: None identified.

Commer

P1910Deficiency of vitamin D in healthy people from a Mediterranean region

Eugenia Cutillas-Marco, MD, Hospital Vega del R�ıo Segura, Cieza, Spain; AmparoFuertes-Prosper, MD, Hospital Doctor Peset, Valencia, Spain; Amparo Marquina-Vila, MD, PhD, Hospital Doctor Peset, Valencia, Spain; Mar�ıa Morales-Su�arez-Varela, MD, PhD, Unit of Public Health and Enviromental Care, Department ofPreventive Medicine, University of Valencia, Valencia, Spain

Background: Vitamin D is synthesized in human skin that is exposed to ultravioletradiation. Only a lesser amount is obtained from food. After hepatic hydroxylation,25-OH-vitamin D (25OH-D) is hydroxylated in the kidneys to 1,25(OH)2D to exert itsendocrine effect on bone, kidneys, and intestine. Beyond its role in homeostasis ofcalcium and phosphorus, vitamin D deficiency has associations with cardiovasculardisease, insulin resistance, development of autoimmune disease, and colon, breast,and prostate cancers, among others. We wanted to know the status of vitamin D inpatients from a Valencia, a city in southern Europe plenty of sunny days all year long.

Methods: The present cross-sectional study included 177 healthy people recruitedfrom healthy workers or our patients’ relatives, attending our dermatology outpa-tient clinic in summer 2009. A questionnaire was given to every participant at thetime of being including in the study, asking about medical history, currenttreatments, phototype, tobacco, height and weight, use of sunscreens, sun expo-sure, and daily intake of vitamin Derich food. A blood test was performed tomeasure serum levels of 25-OH-vitamin D, calcium, phosphorus, and PTHi.

Results: We included 132 females (74.6%) and 45 males (25.4%) from 18 to 84 yearsold. Prevalence of vitamin D insufficiency was 76.2%, including 4.5% of people withsevere deficiency. Age and tobacco use were associated with lower vitamin D levels.Although high daily intake of vitamin D from the diet did not protect frominsufficiency, oral supplements of vitamin D predicted higher vitamin D level.

Conclusion: We found a high prevalence of vitamin D deficiency and insufficiencyamong healthy people in a sunny region of Spain. For that reason, we recommendscreening for deficiency of 25-OH-vitamin D in any person at risk, including allpatients with diseases where sun avoidance is recommended.

cial support: None identified.

Commer

2011

GENODERMATOSES

P2000Recognition of congenital syndromes with subtle expression or latepenetrance: Presentation of tuberous sclerosis complex in adults

Chien-Hui Hong, MD, MS, Department of Dermatology, Kaohsiung, Taiwan;Diane Seibert, PhD, NP, Graduate School of Nursing, Bethesda, MD, UnitedStates; Fumiko Takeuchi, MD, Department of Dermatology, Bethesda, MD, UnitedStates; Cara Olsen, DrPH, Olonda Hathaway, NP, Translational Medicine Branch,Bethesda, MD, United States; Joel Moss, MD, PhD, Translational Medicine Branch,Bethesda, MD, United States; Thomas N. Darling, MD, PhD, Uniformed ServicesUniversity of the Health Sciences, Bethesda, Maryland

Background: Genetic syndromes that typically present in childhood may beoverlooked when symptoms present later in life, especially if adult diseasemanifestations differ from those seen in children.

Objective: To identify the clinical presentation of tuberous sclerosis complex (TSC)diagnosed in adulthood compared to those diagnosed in childhood.

Design and setting: Retrospective analysis of data collected over a 15-year period in atertiary clinical care center at the National Institutes of Health.

Patients: Seventy-nine adult women with TSC referred for screening or evaluation ofpulmonary lymphangioleiomyomatosis.

Main outcome measures: Ages of onset of TSC features and age of TSC diagnosis;signs and symptoms, including results of imaging and pulmonary function tests.

Results: For 31 of the 79 subjects, TSC was diagnosed in childhood (childhooddiagnosis group). Forty-five subjects received their initial TSC diagnosis in adult-hood, of whom 30 had definitive TSC characteristics in childhood but wereundiagnosed for an average of 23 years (delayed diagnosis group), while theremaining 15 did not manifest evidence sufficient for definitive diagnosis until anaverage age of 37 years (adult penetrance group). Those with adult penetrance wereless likely to have seizures and had fewer and later onset of skin lesions than thosediagnosed in childhood. Severity of pulmonary or renal disease did not significantlydiffer among the three groups.

Conclusions: TSC diagnosis may be delayed until adulthood due either to lack ofrecognition or to late disease penetrance. Individuals diagnosedwith TSC later in lifemay have minimal morbidity throughout childhood but remain at risk for potentiallysevere renal and/or pulmonary disease as adults.

cial support: None identified.

Commer

P2001Epidermolytic hyperkeratosis in a newborn with a heterozygous 187Fmutation in the KRT1 gene

Mark Suchter, MD, UMDNJ Robert Wood Johnson Medical School, Somerset, NJ,United States; Amy Pappert, MD, UMDNJ Robert Wood Johnson Medical School,Somerset, NJ, United States; Sandy Milgraum, MD, UMDNJ Robert Wood JohnsonMedical School, Somerset, NJ, United States

Background: Epidermolytic hyperkeratosis (EHK), also known as bullous congenitalichthyosiform erythroderma, is an autosomal dominant inherited ichthyosis char-acterized by erythema, blisters, superficial ulcerations, denuded skin, and palmo-plantar hyperkeratosis that typically spares the hair, nails, and mucosal surfaces.EHK is caused by mutations in the keratin 1 and/or 10 genes.

Case report: A 1-day-old female was noted to have erythema, friable skin, and diffuseskin blistering at birth. She was born at 38 weeks’ gestation and was the product ofan uncomplicated pregnancy to a 34-year-old gravida 3 para 2 female. Family historywas significant only for psoriasis in her father and paternal aunt. Upon delivery, shewas admitted to the neonatal intensive care unit. The physical examination wasnotable for diffuse erythema, large confluent areas of denuded skin and superficialulcerations, and hyperkeratosis of the palms and soles. There were no oral lesions ornail involvement. A skin biopsy specimen revealed hyperkeratosis with acantholysisof the upper epidermis and vacuolar changes in the lower epidermis. Keratinocytesshowed prominent hypereosinophilic intracytoplasmic keratin globules. Electronmicroscopy (EM) of epidermal keratinocytes demonstrated excess tonofilamentswith marked increase in peripheral keratohyaline granules and hemidesmosomesattached to only one cell. Gene analysis was positive for a heterozygous 187Fmutation in the KRT1 gene, confirming the diagnosis of EHK.

Discussion: EHK affects approximately 1 in every 100,000 to 300,000 live births. It isautosomal dominant with 100% penetrance; however, half of the cases are sporadicand caused by spontaneous mutations. EHK typically presents with erythema,blisters, superficial ulcerations, denuded skin, and palmoplantar hyperkeratosis thattypically spares the hair, nails, and mucosal surfaces. Treatment options includekeratolytics, emollients, and topical or systemic retinoids. As patients with EHKgrow older, the bullae and erosions tend to resolve and are replaced withhyperkeratotic skin. There are no extracutaneous manifestations of EHK andpatients live a normal life span.

Conclusion: Because EHK can have a presentation similar to other newbornblistering conditions, such as staphylococcal scalded skin syndrome, epidermolysisbullosa, and other ichthyoses, EM and genetic testing can improve the ability todifferentiate among these conditions.

cial support: None identified.

Commer

J AM ACAD DERMATOL AB83