CongenitalHeartDefect
Syndromes
GROUPI:ECTOMESENCHYMALTISSUEMIGRATIONABNORMALITIES
Ventricularseptaldefect,subarterial
Trisomy18
Deletion22q11.2
(DiGeorge/VCFsyndrome)
Kabukisyndrome
Double-outletrightventricle
Trisomy18
Deletion22q11.2
(DiGeorge/VCFsyndrome)
VACTERLAssociation
TetralogyofFallot
Downsyndrome
Trisomy18
Trisomy13
Deletion8p23
Deletion22q11.2
(DiGeorge/VCFsyndrome)
Microdeletion1q21.1
CHARGEsyndrome
Alagillesyndrome
VACTERLassociation
Oculo-auriculo-vertebral
spectrum(Goldenhar)
TetralogyofFallotwithpulmonaryatresia
Deletion22q11.2
(DiGeorge/VCFsyndrome)
CHARGEsyndrome
Aortopulmonarywindow
VACTERLassociation
CHARGEsyndrome
Truncusarteriosus
Deletion22q11.2
(DiGeorge/VCFsyndrome)
Duplication8q(interstitial)
“Distal”deletion22q11.2
CHARGEsyndrome
GROUPII:INTRACARDIACBLOODFLOWDEFECTS
Ventricularseptaldefect,perimembranous
Trisomy13
Trisomy18
Left-sidedobstructiondefects(bicuspidaorticvalve,aorticcoarctation,aorticvalve Turnersyndrome
stenosis,interruptedaorticarchtypeA,hypoplasticleftheart,aorticatresia,mitral
Deletion11q(Jacobsen
atresia)
syndrome)
Williamssyndrome
Noonan
syndrome/RASopathies
Kabukisyndrome
Atrialseptaldefect,ostiumsecundum
Downsyndrome
Trisomy18
Trisomy13
Holt-Oramsyndrome
Noonan
syndrome/RASopathies
Kabukisyndrome
Pulmonaryvalvestenosis
Deletion4p(WolfHirschhornsyndrome)
Noonan
syndrome/RASopathies
Williamssyndrome
GROUPIII:CELLDEATHABNORMALITIES
Ventricularseptaldefect,muscular
Ebsteinmalformationofthetricuspidvalve
GROUPIV:EXTRACELLULARMATRIXABNORMALITIES
Atrialseptaldefect,ostiumprimum,
Ventricularseptaldefect,typeIII(posterior“atrioventricularcanal”type)
Atrioventricularcanal
Dysplasticaorticorpulmonaryvalve
GROUPV:ABNORMALTARGETEDGROWTHDEFECTS
Anomalouspulmonaryvenousreturn(partial)
Anomalouspulmonaryvenousreturn(total)
Cortriatriatum
Atrialseptaldefect,sinusvenosus
Holt-Oramsyndrome
Trisomy18
Trisomy13
Microdeletion1p36
Deletion8p23
Deletion18q(terminal)
Downsyndrome
Deletion8p23
Deletion3p25
Noonansyndrome
Ellis-vanCreveld
syndrome
Oral-Facial-Digital
syndrome
Smith-Lemli-Opitz
syndrome
CHARGEsyndrome
Tetrasomy22(cat-eye
syndrome)
Trisomy22
Turnersyndrome
Holt-Oramsyndrome
Townes-Brockssyndrome
Oculo-auriculo-vertebral
spectrum(Goldenhar
syndrome)
VACTERLassociation
GeneticCounseling
ClinicalevaluationofpatientswithCHDshouldincludereconstructionoffamily
history,phenotypicevaluation,andscreeningforextracardiacmalformations.If
aspecificsyndromeissuspected,therelatedchromosomaltesting(karyotypeor
fluorescenceinsituhybridizationorarraycomparativegenomichybridization
[CGH]analysis)ortherelatedmolecularanalysis(sequencingbySangertesting
ornext-generationsequencing)shouldbeperformed.Chromosomalanalysisand
arrayCGHareindicatedalsoinsyndromicpatientswithoutaspecificdiagnostic
suspicion.Geneticcounselingtofamiliescanthenbeperformedaccordingtothe
recurrencerisksrelatedtothespecificsyndrome.
ManagementofCongenitalHeartDefectsin
GeneticSyndromes
Inthepast,treatmentofCHDassociatedwithgeneticsyndromeshadbeena
debatedissuefromethicalandtechnicalpointsofview.8,12Nowadaysweknow
thatrecognizingthespecificcardiovascularandextracardiacriskfactors
associatedwitheachsyndromicconditionwillfacilitatemanagement,early
detectionofclinicalproblems,andfinallyimprovethesurgicalresultsinthis
differentgroupofpatients.9,18Themultidisciplinarymanagementofthese
complexchildrenrepresentsthelastchallengeforpediatriccardiologistsand
cardiacsurgeons.Thedevelopmentofsyndrome-baseddiagnosticand
perioperativeprotocolsmustguidetheprophylacticactionsandultimately
improvethespecificoutcomesforthemorefrequentlyencounteredgenetic
syndromes.9Theearlyandaccuratecardiaccareofthesechildrenimprovestheir
survival,contributestothereductionofthehandicap,andimprovesthequality
oflifeofthepatientsandtheirfamilies.Moreover,thegeneticstudiesandthe
clinicalcareofthecomplexcaseswithCHDassociatedwithgeneticsyndromes
havealsoimprovedourknowledgeofpathogenesisandourskillsintreatingall
patientswithsyndromicandnonsyndromictypesofcardiacdefects.