Andersons pediatric cardiology 2069

Themajorityofcongenitalheartdefects(CHDs)occurasisolated
malformations,whereasapproximately25%to30%ofthemareassociatedwith
extracardiacanomalies,inthesettingoflargeorsubmicroscopicchromosomal
anomalies,monogenicmendeliandisorders,andgeneticassociations.1
Furthermore,recentstudiesreportedahigherfrequency(approximately40%)of
detectinganunderlyingdisorderwhenthecohortstudiesweredoneonpatients
withcardiacdefectsrequiringinvasiveorsurgicalinterventions(i.e.,themost
severeforms).2
Moreover,althoughinneonateswithcardiacdefecttheincidenceof
aneuploidyrangesbetween9%and18%,amongfetuseswithprenatally
diagnosedheartmalformationtheincidenceofaneuploidyishigher,ranging
between33%and42%.3Almostall(98%)fetuseswithaneuploidyandcardiac
defecthaveoneormoreextracardiacmalformation.3
ThestrongassociationbetweenCHDandgeneticsyndromesmaybe
explainedbytheimportantcontributionofextracardiactissuestoaccomplisha
normalheartdevelopment.Thisobservation,madebyMariaVictoriadelaCruz
in1977,4wasconfirmedbythediscoveryofasecondheartfieldcontributingto
theformationofoutflowtractandthevenouspoleoftheheart.So,itdoesnot
comeasasurprisethatinthepresenceofageneticsyndrome,whichinvolves
multipleorgans,thecontributionoftheextracardiactissuesrequiredforheart
developmentalsocanbemissing,causinganassociatedCHD.
Neurodevelopmentalanomaliesareoneofthemostimportantproblemsin
childrenwithCHD.Thesecomplicationsaffectapproximately10%ofchildren
withcardiacdefectandabout50%ofthegroupwithsevereheartmalformation5
isprevalentlyinpatientswithassociatedgeneticsyndromes.6
SometypesofCHD,suchasatrioventricularcanaldefect(AVCD)and
conotruncalmalformations,aremorefrequentlyfoundinassociationwith
geneticsyndromessuchasDownordeletion22q11.2syndromes,whereasother
typesareprevalentlyisolateddefects(tricuspidatresia)1,7(Table77.1).
Nevertheless,alltypesofCHDsneedtobeevaluatedbyaclinicalgeneticist.
Specificgenetictestingshouldbeindicatedinpatientswithextracardiac

anomaliesorfamilialrecurrenceofthedisease.Knowledgeinthisareais
evolvingdramatically,andadvancesinmoleculartestingareleadingtothe
identificationofanincreasednumberofcausesofsyndromicandisolatedCHDs.
Table77.1


PrevalenceofExtracardiacAnomaliesintheSettingofGeneticSyndromesinDifferentTypesof
CongenitalHeartDefects
CongenitalHeartDefect
Atrioventricularcanaldefect
Interruptedaorticarch
Truncusarteriosus
Double-outletrightventricle
Atrialseptaldefect
TetralogyofFallot
Aorticcoarctation
Abnormalpulmonaryvenousreturn
Ventricularseptaldefect
Ebsteinanomaly
Pulmonarystenosis
Aorticstenosis
Hypoplasticleftventricle
Tricuspidatresia
Transpositionofthegreatarteries
Pulmonaryatresiaandintactseptum

Frequency(%)
70–80
40–50
40–45

35–40
30–40
30–35
23–25
20–23
18–25
18–23
15–25
15–20
15–20
12–18
10–12
8–12

Historically,thecareofCHDsassociatedwithgeneticsyndromeshasbeenset
asidebecauseoftheircomplexity,resultinginanincreasedriskfordeathand/or
majorcomplications.8Theimprovementinsurgicalrepairofeventhemost
challengingCHDsallowedthesurvivalofthesepatients,switchingour
perspectivefromanexclusivelycardiacoutcometoamultispecialtyapproach,
wherethegeneralwell-beingofachildwithCHDandgeneticsyndromesisour
maingoal.9
Severalphenotype-genotypecorrelationstudiessuggestthatspecific
morphogeneticmechanismsputinmotionbygenescanresultinaspecific
cardiacphenotype.10Theseresultshaveseveralimportantclinicalimplications.
Infact,therecognitionofdistinctcardiacanatomicsubtypesmayhelpin
suggestingaccuratediagnosesandspecificmedicalandsurgicaltherapy.9
Aspecialeffortneedstobemadefortheidentificationofspecificsyndromes
becausethishasadramaticimpactonmanagement,surgicaloutcomes,longtermoutlook,andgeneticcounselingforfuturepregnancies.Amultidisciplinary
approach,withfocusonthespecificriskfactorsrelatedtospecificgenetic
syndromes,canbeusedinthepatients’treatmentandfollow-up.

Besidetheclinicalimplications,thegenotype-phenotypecorrelationshedlight
onembryologicmechanismsthatcontrolcardiacdevelopment,increasingour
knowledgeonthegeneticbasisofCHDalsoinnonsyndromicpatients.11


ChromosomalAnomalies
DownSyndrome
ClinicalFeatures
Downsyndromeischaracterizedbyneonatalhypotonia,developmentaland
cognitivedelay,cardiacandgastrointestinalmalformations,andspecificfacial
anomalies,includingflatface,upslantingpalpebralfissures,epicanthalfolds,
smallnosewithlownasalbridge,anddownturnedsmallmouthwithtendencyto
protrudethetongue(Fig.77.1).Associatedgastrointestinalmalformationinclude
duodenalatresia,Hirschsprungdisease,analatresia,orstenosis(Table77.2).
Additionalmedicalcomplicationscanmanifestasthyroidglandmalfunctioning,
upperrespiratoryinfections,audiologicproblems,orhematologicdiseases.12

FIG.77.1 FacialappearanceofDownsyndrome.