ClinicalFeature
Thumbanomaly
Congenitalheartdefect
Atrialseptaldefect,ostiumsecundum
Ventricularseptaldefect,muscular
TetralogyofFallot
Atrioventricularcanaldefect
Anomalouspulmonaryvenousreturn
Other
Shoulderanomalies
Shorteningoftheupperarm
Radialhypoplasia
Cardiacconductiondisease
Frequency(%)
85
75
40
30
10
5
5
10
75
45
40
40
FIG.77.9 RadialhypoplasiainHolt-Oramsyndrome.
CardiacDefects
Acongenitalheartmalformationispresentin75%ofindividualswithHoltOramsyndrome.Anatomictypesincludeatrialseptaldefectostiumsecundum
typeandventricularseptaldefect,particularlyinvolvingmuscularseptum(see
Table77.11).119,120MorecomplexCHDs,suchastetralogyofFallot,havealso
beendescribed,
PatientswithHolt-OramsyndromewithorwithoutCHDareatriskfor
cardiacconductiondisease,includingsinusbradycardiaandfirst-degree
atrioventricularblock.
GeneticDefect
ThemajorityofthepatientshaveheterozygousTBX5pathogenicvariants,a
genememberofthehomeoboxgenefamilyactingastranscriptionfactor.121
Adams-OliverSyndrome
ClinicalFeatures
Adams-Oliversyndromeisararegeneticdisordercharacterizedbyaplasiacutis
congenitaandterminaltransverselimbdefects(Table77.12).122Cardiacdefects
canbeassociated,suchasstructuralorfunctionalvascularabnormalities.123In
addition,anomaliesininternalorgans,includingthecentralnervous,pulmonary,
gastrointestinal,andgenitourinarysystemshavealsobeendescribed(seeTable
77.12).
Table77.12
PrevalenceofClinicalFeaturesinPatientsWithAdams-OliverSyndrome
ClinicalFeature
Transverseterminallimbdefects
Cutisaplasia
Congenitalheartdefect
Left-sidedobstructivelesions
Septaldefects
Other
Neurologicanomalies
CardiacDefects
Frequency(%)
85
80
25
50
30
20
20
CHDsareoccurringin13%to20%ofthepatients,anddifferentanatomictypes
havebeenreported,includingleft-sidedobstructivelesions,septaland
conotruncaldefects,andtricuspidatresia(seeTable77.12).123–125Left-sided
obstructivelesions,particularlyanomaliesatmultiplelevelscharacteristicof
Shonecomplex(parachutemitralvalve,hypoplasticleftventricle,bicuspid
aorticvalve,andhypoplasticaorticarch),126andvascularabnormalities,of
whichcutismarmoratatelangiectaticacongenitaarethemostfrequently
describedlesions.Othervasculardefectsincludelowerlimbvasculature
abnormalities,portalandcorticalrenalveindefects,anddisordersofthe
pulmonaryvasculature,includingbronchopulmonaryhemangioma,pulmonary
arteriovenousmalformations,andpulmonaryhypertension.123–125
GeneticDefect
Adams-Oliversyndromeisprimarilyinheritedasanautosomaldominanttrait
withvariablephenotypicexpression;autosomalrecessivetransmissionhasalso
beenidentifiedinseveralfamilies.Thesyndromeisaheterogeneousdisorder
withmutationsindifferentgenes.126–128
CHARGESyndrome
ClinicalFeatures
CHARGEisanacronymforocularcoloboma,heartdefects,choanalatresia,
retardedgrowthanddevelopment,genitalabnormalities,andearanomalies
(Table77.13).129Cranialnervedysfunctionresultinginhyposmiaoranosmia,
andunilateralorbilateralfacialpalsyisoftenpresent.Earanomaliesmanifestas
abnormalouterears,ossicularmalformations,Mondinidefectofthecochlea,
andabsentorhypoplasticsemicircularcanals.Growthdeficiency,orofacial
clefts,andtracheoesophagealfistulacanalsobepresent.
Table77.13
PrevalenceofClinicalFeaturesinPatientsWithCHARGESyndrome
ClinicalFeature
Characteristiceardysmorphism
Middleearmalformation
Developmentaldelay
Frequency(%)
80–100
80–100
70–100