Results Interpretation & Application Toolkit

7/27/2019 Results Interpretation & Application Toolkit

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Results Interpretation & ApplicationToolkitInterpretation of results

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Published October 2013

NCHPEG

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Key Points when Interpreting Genetic Testing Results:

The!interpretation!of!a!genetic!result!depends!on!the!context!of!the!individual!and!family.!!! If!a!patient!meets!clinical!criteria!for!a!genetic!syndrome!based!on!his!or!her!medical!and!family!history,!the!patient!should!

be!screened!and!managed!according!to!guidelines!for!the!syndrome,!even!in!the!absence!of!confirmatory!genetic!testing.!

When!testing!an!unaffected!relative,!negative!or!VUS!results!are!not!fully!informative!unless!a!mutation!has!already!been!identified!in!the!family.!

Genetic!test!results!are!not!always!straightforward.!Be!cautious!with!counseling!and!management!changes!when!results!areuninformative!or!VUS.!In!these!cases,!consider!communicating!with!the!lab!or!a!genetics!professional.!

Possible Outcomes of Genetic Testing Table for Child Neurologists

Clinical!Presentation!

of!Person!to!be!Tested!

Genetic!Testing!Result! Interpretation! Recommendations!for!Family!Members!

Affected!or!

symptomatic!

Positive!!

(One!dominant!or!two!

recessive!mutations!

identified)!

True!positive.!DiseaseL

causing!mutation!

identified.!Test!confirms!

clinical!diagnosis.!

MutationLspecific!testing!of!firstLdegree!

family!members!is!strongly!

recommended.!Those!with!positive!

results!are!at!risk!for!developing!the!

disease.!

Affected!or!

symptomatic!

Negative!

(No!dominant!mutations!

found,!one!or!no!recessive!

mutations!identified)!

Genetic!testing!does!not!

rule!out!the!diagnosis!or!a!

genetic!cause!of!the!

disease.!

Testing!of!family!members!not!indicated.!!

However,!clinical!followLup!testing!is!

recommended.!

Affected!or!

symptomatic!

Variant!of!unknown!clinical!

significance!

Genetic!testing!at!this!time!

is!uninformative.!

If!symptomatic!family!members!are!

found!to!have!the!same!variant,!it!is!

more!likely!that!the!variant!is!disease!

causing.!If!family!members!who!do!not!

have!symptoms!have!the!same!variant,!it!

could!be!benign.!!!

Unaffected!or!

asymptomatic!

Positive! Patient!is!at!risk!for!

developing!the!disease.!

Testing!of!family!members!is!

recommended.!Those!with!negative!

results!are!not!at!an!increased!risk!for!

the!disease.!

Unaffected!or!

asymptomatic!

Negative! Patient!is!likely!not!at!

increased!risk!for!the!

disease.!

Testing!of!family!members!is!not!

indicated.!

Unaffected!or!

asymptomatic!

Variant!of!unknown!clinical!

significance!

Genetic!testing!at!this!time!

in!uninformative.!!!

If!symptomatic!family!members!are!

found!to!have!the!same!variant,!it!is!

more!likely!that!the!variant!is!disease!causing.!If!family!members!who!do!not!

have!symptoms!have!the!same!variant,!it!

could!be!benign.!!!

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Results Interpretation & ApplicationToolkitPatient-Centered Communication Tips

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NCHPEG

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Before the Appointment

Schedule!enough!time!to!answer!questions.!! Prepare!graphs!and/or!diagrams!to!help!illustrate!risk!factors.!! Consider!life!experiences!when!providing!risk!information!to!a!patient.!For!example,!individuals!who!have!a!relative!with!a!

similar!neurological!dis?!!order!or!who!have!experienced!rare!or!unusual!events!may!interpret!risk!information!differently.!!!

During the Appointment Try!to!assess!how!your!patients!perceive!their!risk.!Sometimes!giving!a!qualitative!risk!(high,!moderate,!or!average)!can!be!

helpful,!but!often!it!is!best!to!avoid!this!without!first!getting!a!sense!of!what!a!persons!perceived!risk.!Asking!them!about!

their!perceptions!before!and!after!you!provide!quantitative!data!can!also!help!you!frame!a!qualitative!risk.!!

Be!sensitive!to!parents!reactions!!they!may!experience!a!variety!of!emotions!including!guilt,!anger!or!blame.!Emphasize!that!they!are!not!responsible!for!passing!this!disorder!on!to!their!child/!future!children.!!

Use!simple!language!and!discuss!the!symptoms!and!prognosis!for!the!condition!honestly!and!openly.!!

Put!risk!in!perspective!!The!chance!that!your!daughter!would!have!children!who!were!SMA!carriers!would!be!100%,!but!the!chance!that!they!would!also!have!!SMA!is!closer!to!1!in!1340!or!less!than!1%.!!

Provide!risk!information!in!at!least!two!different!ways.!For!example,!Your!risk!of!having!another!child!with!SMA!is!about!1!in!4.!This!is!the!same!as!!saying!your!risk!is!about!25%.!!

When!providing!a!lifetime!risk,!make!sure!to!include!the!baseline!risk!for!comparison!!The!average!womans!lifetime!risk!of!developing!Alzheimers!disease!is!about!5%!by!age!80.!Individuals!with!mild!cognitive!impairment!!and!the!e4!APOE!variant!

have!an!increased!risk!of!34%!in!the!next!several!years.!!

Emphasize!positives,!such!as!In!my!experience!children!with!this!diagnosis!are!very!happy!and!engaged.!! Make!sure!parents!understand!recurrence!risk!for!future!pregnancies!and!have!someone!to!speak!to!about!these!concerns!

and!options.!Consider!referring!to!a!genetics!professional!when!discussing!recurrence!risk!and!these!options.!!Consider!

referring!to!a!genetics!professional!when!discussing!recurrence!risk!and!these!options.!

For Follow-up Provide!a!plan!for!follow!up.!! Provide!resources!and!referral!as!appropriate.!!

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Results Interpretation & ApplicationToolkitCommunicating genetic testing results

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NCHPEG

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Communicating!the!results!and!limitations!of!genetic!testing!clearly!and!compassionately!is!important!to!help!patients!and!their!

families!adapt!to!results,!make!informed!decisions!and!convey!appropriate!information!to!their!relatives.!Be!aware!of!potential!

psychosocial!concerns!with!genetic!testing!and!results.!

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Prior to the communicationo Identify!goals!and!information!needed!to!provide!during!the!conversation!(come!up!with!two!versions:![1]!all!points!you!

would!like!to!cover!and![2]!Bare!minimum!they!need!to!take!away.)!

o Determine!who!should!be!present!at!the!time!of!disclosure!(and!if!there!should!be!a!meeting!post!disclosure!with!additionapeople).!

o Identify!the!room/setting!where!the!meeting!will!occur.!An!exam!room!is!usually!the!easiest!option!but!often!a!small!conference!or!counseling!room!may!be!more!appropriate.!

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Phone Communicationo Make!sure!that!this!is!still!a!good!time!to!talk,!and!that!they!are!not!driving!or!distracted.!o Identify!if!there!are!additional!people!that!should!be!there!for!support!(ensure!that!they!are!there!before!beginning).!o Find!a!quiet,!uninterrupted!place!to!make!a!phone!call.!o Allow!for!enough!time!to!talk!and!be!reKcontacted!if!spouse/other!family!members!need!to!ask!further!questions.!!

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In-Person Communicationo Have!everyone!sitting!(same!level).!o Have!tissues!in!the!room!prior!to!patients!entering!the!room.!o Minimize!distractions.!o Provide!enough!time.!

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Providing Resulto Review!the!purpose!of!testing,!procedures,!and!possible!outcomes.!o Ask!the!patient/family!if!they!are!ready!to!hear!the!results.!o Use!simple!language.!o Discuss!prognosis!honestly!and!openly.!

Assess Reactions and Respondo Allow!a!moment!of!silence!for!the!patient/family!to!process!the!information!and!ask!questions.!o Use!openKended!questions!to!assess!how!they!are!absorbing!the!information.!!o Give!permission!for!emotions!and!normalize!reactions.!o Use!language!that!empowers!the!family!to!care!for!the!child.!!o Assess!the!familys!support!structure!and!provide!resources!and!referral!as!appropriate.!o Emphasize!concrete!next!steps!and!a!clear!plan!for!followKup.!

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Results Interpretation & ApplicationToolkitManagement

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NCHPEG

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Management!of!individuals!with!genetic!syndromes!often!includes!screening!and!treatment!for!the!multi6systemic!features!

associated!with!the!specific!syndrome,!developmental!and!educational!assessment,!and!screening!for!at6risk!relatives.!The!purpose!of!this!tool!is!to!help!you!identify!resources!that!can!aid!in!the!development!of!a!comprehensive!management!plan!for!your!patient!

and!his!or!her!family!for!a!variety!of!genetic!syndromes.!!

National Guidelines Clearinghouse

guideline.gov/!

The!National!Guidelines!Clearinghouse!is!a!publicly!available!resource!that!provides!access!to!evidence6based!clinical!practice!

guidelines.!Use!the!Clearinghouse!to!search!for!guidelines!about!management!of!a!specific!syndrome.!!!

GeneFacts

www.genefacts.org!!!!

GeneFacts!are!fact!sheets!designed!to!be!used!at!the!point!of!care!in!clinic.!Each!condition6specific!fact!sheet!includes!guidance!on!

risk!assessment,!diagnosis,!testing,!and!management,!with!links!for!evidence6based!and!professional!society!guidelines.!!

Unique

www.rarechromo.org!!!!

Unique!is!a!family!support!group!for!rare!chromosomal!conditions.!They!provide!information!to!families,!health!professionals,!and!

the!public!about!many!different!chromosomal!conditions.!Click!on!Professionals!and!Disorder!Leaflets!to!access!condition6specific!

information.!!

GeneReviews

www.ncbi.nlm.nih.gov/books/NBK111!!

GeneReviews!are!expert6authored,!peer6reviewed,!current!disease!descriptions!that!apply!genetic!testing!to!the!diagnosis,!

management,!and!genetic!counseling!of!patients!and!families!with!specific!inherited!conditions.!!

Genetics education materials for school success: GEMSS

www.gemssforschools.org!!

The!aim!of!GEMSS!is!to!assure!all!children!with!genetic!health!conditions!succeed!in!school6life.!This!resource!includes!information!

about!medical/dietary!needs,!education!supports,!behavior!and!sensory!supports,!physical!activity,!school!absences,!and!emergency

planning!for!certain!genetic!conditions.!!

OMIM: Online Mendelian Inheritance in Man

omim.org/!

OMIM!is!a!frequently6updated!online!catalog!of!genetic!syndromes!and!gene!associations.!The!full6text,!referenced!overviews!

contain!information!on!all!known!genetic!syndromes.!Use!the!links!on!the!right!hand!side!of!the!page!to!find!related!resources.!

Management of Genetic Syndromes

S.!B.!Cassidy,!&!J.!E.!Allanson!(Eds.).!(2010).!Management(of(genetic(syndromes( (3rd!edition).!Hoboken,!N.J.:!John!Wiley!&!Sons,!Inc.!

National Institutes of Health Clinical Trials Databasewww.clinicaltrials.gov !!!


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2012

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Results Interpretation & Application ToolkitCollaborating with and referring to genetics

!Genetic!counseling!is!the!process!of!helping!people!understand!and!adapt!to!the!medical,!psychological!and!familial!implications!

of!genetic!contributions!to!disease.!!This!process!integrates!risk!assessment,!education,!and!counseling.!In!some!cases,!it!includes!

the!offer!and!interpretation!of!genetic!testing.!The!purpose!is!to!help!the!patient!and!family!to!interpret!and!adapt!to!the!genetic!

information,!and!make!informed!decisions!based!on!his!or!her!understanding!of!risks.

Genetic!counseling!is!best!provided!by!specialists!with!knowledge!and!experience!in!clinical!genetics,!such!as!genetic!counselors,!

physician!geneticists,!and!advanced!practice!nurses!trained!in!genetics.! All!providers,!however,!play!a!role!in!the!genetic!counseling

process!by:!

!! identifying!patients!who!would!benefit!from!genetic!counseling,!including!patients!who!have!personal!or!family!histories!

suggestive!of!a!hereditary!syndrome;!

!!providing!referral!to!genetic!counseling!services,!

!! informing!patients!about!the!reasons!for!and!benefits!of!genetic!counseling;!

!!helping!patients!identify!what!family!medical!information!will!be!necessary!for!risk!assessment;!

!!using!the!outcome!of!the!genetics!consultation!to!identify!screening,!risk!reduction,!and!management!plans;!and!

!!answering!questions!for!patients.!

Genetic!counseling!is!also!appropriate!for!patients!at!increased!risk!who!do!not!wish!to!pursue!genetic!testing,!and!in!

cases!where!the!patients!risk!status!is!uncertain.!!For!questions!about!the!need!for!referral,!consult!with!the!specialist.!

!!!!!

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Locating A Genetics Professional!

American College of Medical Genetics:www.acmg.net

National Society of Genetic Counselors:

www.nsgc.org

GeneTests Clinic Directory:

www.genetests.org


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Checklist for Collaboration with a Genetics ProfessionalHow!to!use!this!tool:!!This!tool!outlines!the!information!you!should!include!when!referring!a!patient!for!genetic!evaluation.!!You!can!

print!and!fill!it!out!for!a!patient,!adapt!it!to!use!as!a!clinic!form!in!your!own!practice,!or!transcribe!the!elements!into!an!electronic!

referral!form!or!template.!

Reason for Referral/History of Presenting Illness:!

!!!!

Developmental History!

! On time () Delayed () Regression ()

Gross Motor ! ! !

Fine Motor ! ! !

Speech ! ! !

Review of Systems and Physical Exam!

() if normal

Constitutional ! Musculoskeletal !

Eyes ! Skin !

ENT/Audiology ! Psychiatric !

Cardiovascular ! Endocrine !

Respiratory ! Hematology !

Gastrointestinal ! Allergy !

Genitourinary ! Immunology !

Comments: ! ! !

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Labs / Studies!

! Normal () Abnormal () If abnormal, explain

EEG ! ! !

EMG ! ! !

BAER ! ! !

MRI ! ! !

CT ! ! !

LP ! ! !

Metabolic ! ! !

Genetic ! ! !

Family History!

! () if

applicable

Describe relationship to patient

DD ! !

MR/ID ! !

Stroke ! !

Headache/

Migraines

! !

Seizures ! !

Consanguinity ! !

Other ! !

Unremarkable ! !

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Documents

Results Interpretation & Application Toolkit