Familial vs. Hereditary Disease: Definitions and Key ...

'Hereditary' is most commonly used when referring to diseases with a known genetic cause · 'Familial' disorders are those which appear to have a ... COVID-19 Alerts OB 2TUSAtlas TheGenome GYN GYN SexualHealth PrimaryCare YourPractice GrandRounds MyBookshelf Now@ObG Media AboutUs ContactUs Login ObGFirst Togglenavigation COVID-19 Alerts OB 2TUSAtlas TheGenome GYN GYN SexualHealth PrimaryCare YourPractice GrandRounds MyBookshelf Now@ObG Media TheGenome CMECNE Familialvs.HereditaryDisease:DefinitionsandKeyCounselingPoints LearningObjectivesandCME/DisclosureInformationThisactivityisintendedforhealthcareprovidersdeliveringcaretowomenandtheirfamilies.Aftercompletingthisactivity,theparticipantshouldbebetterableto:1.Describewhyreducedpenetranceorvariableexpressivitymaycomplicateapedigree2.DiscussthedifferencesbetweenhereditaryvsfamilialdiseaseEstimatedtimetocompleteactivity:0.25hoursFaculty:SusanJ.Gross,MD,FRCSC,FACOG,FACMG PresidentandCEO,TheObGProjectDisclosureofConflictsofInterestPostgraduateInstituteforMedicine(PIM)requiresfaculty,planners,andothersincontrolofeducationalcontenttodisclosealltheirfinancialrelationshipswithineligiblecompanies.Allidentifiedconflictsofinterest(COI)arethoroughlyvettedandmitigatedaccordingtoPIMpolicy.PIMiscommittedtoprovidingitslearnerswithhighqualityaccreditedcontinuingeducationactivitiesandrelatedmaterialsthatpromoteimprovementsorqualityinhealthcareandnotaspecificproprietarybusinessinterestofanineligiblecompany.ThePIMplannersandothershavenothingtodisclose.TheOBGProjectplannersandothershavenothingtodisclose.Faculty:SusanJ.Gross,MD,receivesconsultingfeesfromCradleGenomics,andhasfinancialinterestinTheObGProject,Inc.PlannersandManagers:ThePIMplannersandmanagers,TraceHutchison,PharmD,SamanthaMattiucci,PharmD,CHCP,JudiSmelker-Mitchek,MBA,MSN,RN,andJanSchultz,MSN,RN,CHCPhavenothingtodisclose.MethodofParticipationandRequestforCreditFeesforparticipatingandreceivingCMEcreditforthisactivityareaspostedonTheObGProjectwebsite.Duringtheperiodfrom8/30/2021through12/15/2022,participantsmustreadthelearningobjectivesandfacultydisclosuresandstudytheeducationalactivity.Ifyouwishtoreceiveacknowledgmentforcompletingthisactivity,pleasecompletethepost-testandevaluation.Uponregisteringandsuccessfullycompletingthepost-testwithascoreof100%andtheactivityevaluation,yourcertificatewillbemadeavailableimmediately.ForPharmacists:Uponsuccessfullycompletingthepost-testwithascoreof100%andtheactivityevaluationform,transcriptinformationwillbesenttotheNABPCPEMonitorServicewithin4weeks.JointAccreditationStatementInsupportofimprovingpatientcare,thisactivityhasbeenplannedandimplementedbythePostgraduateInstituteforMedicineandTheObGProject.PostgraduateInstituteforMedicineisjointlyaccreditedbytheAccreditationCouncilforContinuingMedicalEducation(ACCME),theAccreditationCouncilforPharmacyEducation(ACPE),andtheAmericanNursesCredentialingCenter(ANCC),toprovidecontinuingeducationforthehealthcareteam.PhysicianContinuingMedicalEducationPostgraduateInstituteforMedicinedesignatesthisenduringmaterialforamaximumof0.25AMAPRACategory1Credit(s)™.Physiciansshouldclaimonlythecreditcommensuratewiththeextentoftheirparticipationintheactivity.ContinuingNursingEducationThemaximumnumberofhoursawardedforthisContinuingNursingEducationactivityis0.25contacthours.ReadDisclaimer&FinePrint SUMMARY: Theterms‘hereditary’and‘familial’aresometimesusedinterchangeably,butaretwodifferentconcepts ‘Hereditary’ismostcommonlyusedwhenreferringtodiseaseswithaknowngeneticcause’Familial’disordersarethosewhichappeartohaveageneticcomponent,affectingmorefamilymembersthanwouldbeexpectedbychancealoneHowever,asinglegeneticcauseorexplanationisnotknownHereditaryDisease Generallysinglegenedisorderscanoften,butnotalways,beconfirmedbyagenetictestCertaingeneticdiseasescanbeidentifiedbaseduponclinicaldiagnosisalone,withoutgenetictestingorevenevaluationofafamilyhistoryForexample,Marfansyndrome(see‘LearnMore–PrimarySources’below)isanexamplewhereadiagnosiscanbemadebasedonmeetingcertainclinicalcriteriaIfageneticcauseisfoundCascadetestingcanbehelpful,wherememberswhoareseeminglyunaffectedbydiseasecanalsobetestedtodetermineiftheyareatriskforfuturediseasedevelopment(see‘RelatedObGEntries’below)FamilialDisease UsuallyoccursinmoreindividualsinafamilythanexpectedbychanceGeneticandenvironmentalfactorscoupledwithfamilyhistoryplayaroleindeterminingtheindividuals’riskForexample:AnindividualpresentswithhighbloodpressureandheartdiseasewithafatherwhohadanMIatage65|WhiletherearesinglegenedisordersassociatedwithCVD,inthemajorityofcasesthisscenariowouldbeconsideredfamilial|Notethatotherimportantbehavioralfactorsalongwithfamilyhistorywouldimpactriskandoutcomes(e.g.,sedentarylifestyleandhighfatdiet) ImportantConceptsthatCanMakeDifferentiatingBetweenFamilialandHereditaryDisordersMoreChallenging Variableexpressivity:asinglegenedisordermaypresentdifferentlyinmultiplefamilymembersInthecaseofapathogenicvariantinBRCA1,onewomanmightdevelopbreastcancerat45,whileherbrotherdevelopsprostatecancerat72,eventhoughbothsiblingscarrythesameexactmutationReducedPenetrance:apersonisknowntocarryageneticmutation(eitherthroughagenetictestortheyareanobligatecarrierofthemutation)buttheydonotexhibitsymptomsofthatdiseaseInthecaseofBRCA1:thefatherofthechildrenabove,carriesthepathogenicBRCA1variant–butheis85andneverdevelopedcancerNote:Wheninheritancepatternsareclearcut(e.g.autosomaldominantpatternwithmultipleaffectedfamilymembers),determiningthatadisorderishereditaryandlikelydueasignificantpathogenicvariantiseasier|Unfortunately,variableexpressivityandreducedpenetrancecancomplicatethepresentation|Geneticexpertisecanbehelpfulforpedigreeanalysistodistinguishbetweenfamilialandhereditarydiseaseandpotentialrisks  DifferentiatingBetweenHereditaryorFamilialDisease DeterminingwhetheradisorderishereditaryrequiresadetailedevaluationoffamilyhistoryReviewbyatrainedgeneticsprofessionalwithcarefulattentiontodetailcanbehelpfulTypicallyincludesathree-generationpedigreewithagesofdiagnosesGenetictestingisanimportantwaytodetermineifadiseaseis‘Hereditary’or‘Familial’Knownpathogenicvariantisidentified:Diseaseconsidered‘hereditary’Nopathogenicvariantidentified,yetastrongfamilyhistoryofdiseaseispresent:Diseaseconsidered‘familial’(unlessagenetic/hereditarydiagnosiscanbemadebasedonclinicalfeaturesalone)KEYPOINTS: Manydisordershaveanimportantgeneticcomponent,butarenotcausedbyaknowninheritedchangeinaparticulargeneWhencounselingpatients,thefollowingarepotentialreasonsthatadisordercanappeartobetrackingmorefrequentlywithinafamilybutnodefinitivegeneticanswerhasyetbeenfoundThecausativegenehasnotyetbeendiscoveredPerhapsnumerousgenesandenvironmentalfactorsareleadingtothefamilialriskPerhapsourcurrenttechnologycannotuncoverthegeneticmutationunderlyingtheconditionKnowingthataconditionrunsinafamily,whetherhereditaryorfamilial,canhelpindividualsmakeproactivelifestyledecisions,inthehopesthatitwillreducetheirriskfordiseaseForexample,thereareprophylacticsurgeriesthatmaybeofferedwomenwithBRCApathogenicvariantssuchasriskreducingmastectomy(see‘LearnMore–PrimarySources’below)Generally,hereditarydisorderswillcarryhigherriskforfamilymembersandoffspring(e.g.,carriersofBRCApathogenicvariantsvsthosewithsomeaffectedrelatives,butnoknownmutations)ItcanstillbehelpfultoknowifaconditionisfamilialbecausetheremaybedifferencesinmedicalrecommendationsforthepatientandfamilyForexample,theGailCalculatorconsidersfamilyhistoryinassessingawoman’s5-yearandlifetimeriskforbreastcancerandcaninformwhetherriskreducingmedications(e.g.,raloxifene)shouldbeoffered(see‘LearnMore–PrimarySources’below)ReferraltoageneticcounselorcanbeveryhelpfultodistinguishbetweenfamilialorhereditarydiseaseLearnMore–PrimarySources: ACOG:FamilyHistoryasaRiskAssessmentTool Children’sWisconsin:Multifactorialinheritance MedlinePlus:WhatisHeritability? 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