Andersons pediatric cardiology 2073

FIG.77.4 Facialappearanceofdeletion22q11.2syndrome.

Table77.5
PrevalenceofClinicalFeaturesinPatientsWithDeletion22q11.2Syndrome
ClinicalFeature
Facialanomalies
Learningdifficulties
Congenitalheartdefect
Pulmonaryatresiawithventricularseptaldefect
TetralogyofFallot
Ventricularseptaldefect,subaortic
Interruptedaorticarch
Truncusarteriosus
Vascularring
Atrialseptaldefect
Other
Immunedeficiency
Palatalanomalies
Neonatalhypocalcemia
Renalanomalies
Skeletalanomalies
Ocularanomalies
Analanomalies

Frequency(%)
100
70–90
75
25
25
15

10
10
8
5
2
75
70
50
30
15
7
2


CardiacDefects
CHDsarepresentin75%ofpatientswithdeletion22q11.2;commonly,
conotruncaldefectsarethemajorcauseofmortality(>90%ofalldeaths).
AnatomictypesincludetetralogyofFallot,pulmonaryatresiawithventricular
septaldefect,interruptedaorticarch,mainlytypeB,truncusarteriosus,and
ventricularseptaldefect(seeTable77.5).44–46Commonlyseenaorticarch
anomalies,eitherinisolationorinassociationwithintracardiacanomalies,are
cervicalaorticarch,doubleaorticarch,right-sidedaorticarch,andabnormal
originofthesubclavianarteries.47Asubsetofaffectedindividualsarefoundto
havedilatedaorticroot.48
Thesyndromeissometimesassociatedwithpeculiaraspectsofcardiac
anatomy.Infact,discontinuity,diffusehypoplasia,crossingofthepulmonary
arteries,andmajoraortopulmonarycollateralarteriesmayberecognizable
patternsfortetralogyofFallot(alsointhesettingofanabsentpulmonaryvalve)
andforpulmonaryatresiawithventricularseptaldefect.Discontinuityofthe
pulmonaryarteriesmaybecharacteristicfortruncusarteriosustypeA3

(accordingtoVanPraaghclassification),whereashypoplasiaofinfundibular
septumispresentinbothtetralogyofFallotandinterruptedaorticarch.46,49–51
Theanalysisofsurgicalresultsshowthattheseadditionalcardiacdefectsdo
notworsensurgicalprognosis,anddeletion22q11.2doesnotrepresentasurgical
riskfactorwhensyndrome-specificperioperativemanagementisadopted.Longtermsurvivalofpatientswithconotruncalcardiacdefectsanddeletion22q11.2is
similartothatofpatientswithnonsyndromicconotruncaldefect.Patientswith
pulmonaryatresiaandmajoraortopulmonarycollateralarteriesareanexception
intermsofmortalityrisk,probablyduetothecomplexityofthepulmonary
arteryanatomy.52–54
Majorsystemictopulmonarycollateralsmayberesponsiblefor
bronchomalaciaandpersistentairwayhyperresponsivenesswithbronchospasm
inthepreoperativeandpostoperativeperiods.Inpatientswithdeletion22q11.2,
theperioperativecareshouldbefocusedonpreventionofhypocalcemiaand
infections,includinganalysisoflymphocytepopulationspriortotransfusion,
administrationofirradiatedbloodproducts,andaggressivetreatmentof
perioperativeinfections,andperhapsantifungalprophylaxisinselected
situations.39


GeneticDefect
Thesyndromeiscausedbymicrodeletionsinthe22q11.2chromosomalregion.
Mostpatientshavea3-Mbdeletion,resultingfromnonallelichomologous
recombinationbetweenthetwolargestlow-copyrepeatsflankingtheDiGeorge
criticalregion.41,55Morethan40genesmapwithintheDiGeorgecriticalregion.
TBX1geneisknowntobeacrucialgeneinthesyndromeandlikelyresponsible
formanyheartandvascularanomalies.56Consideringthehighlyvariable
phenotypicexpressionofthesyndrome,itispossiblethatdeletion22q11.2alone
cannotexplainallthemanifestationsofthedisease,andthesensitivityof
individualgeneswithinthe22q11.2regiontogenedosagevariantsand
additional“modifying”variantsoutsidethe22q11.2regionalsoaccountforthe

manifestations.11,57

WilliamsSyndrome
ClinicalFeatures
Williamssyndromeischaracterizedbytypicalfacialanomalies,CHD,
connectivetissueabnormalities,motordevelopmentaldelayandhypotonia,
intellectualdisability,feedingdifficultiesininfancy,growthabnormalities,and
endocrineanomalies(hypercalcemia,hypothyroidism,andearlypuberty)(Table
77.6).58,59Facialanomaliesincludebitemporalnarrowing,periorbitalfullness,a
stellateirispattern,strabismus,malarflattening,shortnosewithanteverted
nares,longphiltrum,widemouthwiththicklips,andlargeearlobes(Fig.77.5).
Table77.6
PrevalenceofClinicalFeaturesinPatientsWithWilliamsSyndrome
ClinicalFeature
Facialanomalies
Developmentaldelay
Shortstature
Congenitalheartdefect
Supravalvaraorticstenosis
Peripheralpulmonaryarterystenosis
Septaldefect
Coarsevoice
Lowbirthweight
Microcephaly
Strabismus

Frequency(%)
100
90
85

80
70
20
10
80
80
70
45