Andersons pediatric cardiology 2280

adultatheroscleroticcardiovasculardiseaseburden.


FamilialScreening(General)
Cardiovascularabnormalitiesmayhaveunderlyinggeneticetiologieswith
variabledegreesofinheritanceandpenetrance.Assuch,familialcardiovascular
screeningmaybeindicatedtoidentifyaffectedfamilymembersaswellasthe
extentoffamilialinvolvement.Twobroadcategoriesinwhichfamilialscreening
isindicatedareaortopathiesandcardiomyopathies.
Inheritedaortopathieshavemanydifferentetiologieswithbicuspidaortic
valve(BAV)beingthemostcommon.BAVisthemostcommoncongenitalheart
defectwithaprevalenceintheadultpopulationof0.5%to2%.116–124BAVfalls
intothespectrumofleft-sidedheartlesionsandcanoccurinisolationorwith
otherleft-sidedlesionssuchascoarctationoftheaorta,mitralvalve
abnormalities,andhypoplasticleft-heartsyndrome.Inaddition,itcanbefound
inpatientswithconnectivetissuedisorders,suchasMarfanorLoeys-Dietz,and
geneticsyndromes,suchasTurnerandWilliamssyndrome.Themorphologically
abnormalaorticvalvemayhavenormalfunctioninthepediatricpatient,butmay
alsobestenoticand/orinsufficient.Althoughprogressivevalvedysfunctionis
commoninpatientswithaBAV,aorticrootand/orascendingaorticdilationis
presentinapproximately50%ofadults.123BAVwithaorticaneurysmisarisk
factorfordevelopingaorticdissections,whichcarryahighmorbidityand
mortality.125
FamilialclusteringofBAVwithorwithoutaorticdilationhasbeen
demonstratedinmultiplestudies.TheprevalenceofBAVinfirst-degreerelatives
isapproximately9%.120Becauseofthepotentialforsignificantmorbidityand
mortalityrelatedtoBAVandasymptomaticaorticdilationleadingtodissection,
currentguidelinesrecommendechocardiographicscreeninginadultsforallfirstdegreerelativeswithBAV.126Inthepediatricpopulation,BAVisoften
discoveredduetoamurmurthatmayberelatedtoaorticvalvedysfunction.As
such,screeningoffirst-degreerelativesisoftenrecommendedatthetimeof
diagnosisofthepediatricpatientwithBAV.Cost-benefitanalysishassuggested

thatwhilecostofscreeningofsiblingsismoderate,thebenefitsofearly
diagnosisandsurveillancesupportscreeningofsiblingsofpatientswithBAV
outweighthecost.127Oneofthechallengesintheserecommendationsiswhen
adultandpediatricprovidersareseparatedclinically,andneithermay
recommendscreeninginthe“other”agerange.


Thegeneticsofleft-sidedheartlesions,includingBAV,arenotfully
understood.Studieshaveshownthataorticrootdilationinthepresenceofa
normalaorticvalveisprevalentin32%offirst-degreerelativesofpatientswith
BAV.128Infamiliesofpatientswithhypoplasticleft-heartsyndrome,atleastone
othercardiovascularmalformationwasfoundin27%offamiliesstudied.129
Becauseoffindingssuchasthese,itisreasonabletoconsidernotonlyaninitial
screeningoffirst-degreerelatives,butalsoperiodiclong-termscreeningto
assessforprogressiveaortopathies.This,however,hasnotbecomeastandard
guideline.
Whileaortopathy,progressiveaorticdilation,andriskofdissectionare
featuresassociatedwithBAV,thesefindingsarealsoseenininheritable
syndromessuchasTurnersyndrome,connectivetissuedisorders,andfamilial
thoracicaorticaneurysmanddissection(FTAAD).Thegeneticsoftheformer
disordersarecomplexandfamilialscreening,whichwillnotbecoveredherein
detail,ofteninvolvesgeneticcounselingandevaluationwithacomprehensive,
multisystemapproachbeyondisolatedcardiovascularscreening.FTAAD,
however,doesnotinvolveotherorgansystemsoutsidethecardiovascular
system.Approximately20%ofpatientswithanaorticaneurysmordissection
haveafamilyhistorysuggestingageneticaortopathy.130,131Severalgeneshave
beenidentifiedasinvolvedinFTAAD;however,notallmutationshavebeen
identified.Currentguidelinesrecommendaorticimaging,typicallybeginning
withechocardiography,infirst-degreerelativesofpatientswithFTAAD.Ifa
geneticmutationhasbeenidentified,geneticcounselingandscreeningoffirstdegreerelativesfortheidentifiedmutationshouldbeconsideredwithfocused

imagingofthosepatientswhocarrythemutation.Incasesinwhichthoracic
aorticaneurysmsarediscoveredinoneormorefirst-degreerelatives,expanded
screeningtosecond-degreerelativesandreferraltogeneticsshouldbe
considered.126
Duetothecomplexnatureofinheritedaortopathiesaswellasevolving
knowledgeandtestingofgeneticmutations,ithasbeenourinstitutional
approachtoevaluatethesepatientsinainterdisciplinaryfashionincluding
cardiologistsandgeneticists,withsubsequentsubspecialtyreferralsasnecessary.

RecommendedScreeningforAortopathies
1.Patient(adultorpediatric)withBAV