Andersons pediatric cardiology 2080

ocularepibulbardermoid,andcervicalvertebralmalformations(Table77.15).144
CongenitalmalformationsincludedinthespectrumareCHD,renalanomalies,
andrarelycentralnervoussystemmalformations.144–146
Table77.15
PrevalenceofClinicalFeaturesinPatientsWithGoldenharSyndrome
ClinicalFeature
Mandibularhypoplasia
Microtia
Preauriculartags
Conductivehearingloss
Velopharyngealinsufficiency
Congenitalheartdefect
Conotruncalheartdefect
Septaldefects
Abnormalpulmonaryvenousreturn/scimitarsyndrome
Situsandloopingdefects
Left-sidedobstructions
Other
Cervicalspinemalformation
Epibulbardermoid
Cleftlipand/orpalate
Sensorineuralhearingloss
Colobomaoftheuppereyelid
Limbanomalies
Genitourinarymalformation
Pulmonaryanomaly

Frequency(%)
100
70–90
40–60

60
55
30–50
40
30
15
7
4
4
20–40
35
22
15
15
10
10
8

CardiacDefects
ThefrequencyofCHDsinGoldenharsyndromeisvaryingindifferentseries,
rangingfrom5%to60%inseveralstudies.ThemostcommonCHDsare
conotruncalandseptaldefects(seeTable77.15).146,147Conotruncalheartdefects
includetetralogyofFallot(classicorwithpulmonaryatresia),subaortic
ventricularseptaldefect,double-outletrightventricle,anddoubleaorticarch.
Cardiaclateralitydefectsinthesettingofvisceralheterotaxiahavealsobeen
reported.Pulmonaryanomaliesassociatedwithvasculardefects,including
Scimitarsyndrome(anomalousconnectionoftherightpulmonaryveinstothe
inferiorvenacava)associatedwithhypoplasticrightpulmonaryarteryandlung,
havebeendescribed.147ThepresenceandthetypeofCHDistheclinicalfeature
thatmostcommonlyinfluencesprognosisofindividualswithGoldenhar

syndrome.

GeneticDefect
ThediagnosisofGoldenharsyndromeisbasedonclinicalfindingsbecausethe
geneticbasisisatpresentunknown.Apathogeneticroleofneuralcrestcell
migrationabnormalities148inagroupofpatientswithoculo-auriculo-vertebral
spectrumcouldhypotheticallyexplaintheoccurrenceofconotruncalheart
defectsandmainphenotypicalfeatures,includingear,mandible,andneck
malformations.Heterogeneityofcardiacdefectscouldberelatedtodifferent
pathogeneticcausesofthesyndrome.Infact,environmental,heritable,and
multifactorialcausesarehypothesizedtobeimplicated.149Maternal
environmentalriskfactorsincludetheuseofvasoactivedrugs,maternaldiabetes
mellitus,multiplegestations,andtheuseofassistedreproductivetechnologies.
Inaddition,severalchromosomalregionsorgenesarebeingevaluatedforcausal
relationship.


Heterotaxy
Theheterotaxysyndromeischaracterizedbycombinationofabnormal
arrangementoftheabdominalandthoracicorganswithcomplexCHDs,
includingAVCD,commonatrium,anomaloussystemicandpulmonaryvenous
drainage,persistentleftsuperiorvenacavawithunroofedcoronarysinus,and
conotruncaldefects.150Severalsyndromescanbeassociatedwithpartialor
completemanifestationsofheterotaxy,includingpolydactylysyndromes(oralfacial-digital,EVC,shortribpolydactyly,Smith-Lemli-Opitz,Bardet-Biedl,
hydrolethalus,andJoubertsyndromes)andVACTERLassociation.97Acommon
pathogeneticbasisbetweencardiaclateralitydefectsandthesesyndromeshas
beenevidencedbecausemolecularstudieshavedemonstratedthatseveralgenes
responsibleforsyndromeswithheterotaxyarecausallyinvolvedinciliary

functionand/orabnormalprocessingofproteinswithroleinHedgehog
signaling.95,151–153Hedgehogsignalingcoordinatesmultipleaspectsofleft-right
lateralizationandcardiovasculargrowth.Inaddition,SonicHedgehogknockout
miceshowCHDsinthesettingofheterotaxyandleftpulmonary
isomerism.154,155Ithasbeenfoundthatperturbationsofthedifferent
componentsofSonicHedgehogpathwayareassociatedwithdifferent
developmentalerrorsinpatientsmanifestingpartiallyoverlapping
features.156,157Thecommoncardiacmanifestationsofciliopathiesarepartial
atrioventricularcanalwithcommonatriumandpersistentleftsuperiorvena
cava.97

TypesofAnatomicCongenitalHeartDefectsand
AssociatedSyndromes
PatientswithspecificgeneticsyndromesoftenpresentCHDsrelatedthroughthe
pathogeneticbasis.10,158Themorecommonidentifiableassociationsforthe
differentpathogeneticgroupsareshowedinTable77.16.
Table77.16
GeneticSyndromesAssociatedtoSpecificPathogeneticGroupsof
CongenitalHeartDefect