FIG.77.3 Facialappearanceofdeletion8p23syndrome.
Table77.4
PrevalenceofClinicalFeaturesinPatientsWithTerminal8pDeletion
ClinicalFeature
Developmentaldelay/learningdifficulties
Congenitalheartdefect
Atrioventricularcanaldefect(withorwithoutpulmonaryvalvestenosis)
Pulmonaryvalvestenosis(alone)
Atrialseptaldefect
TetralogyofFallot
Heterotaxia
Other
Facialanomalies
Microcephaly
Hypospadia
Cryptorchidism
Epilepsy
Frequency(%)
100
70
60
15
10
5
5
5
65
55
40
30
25
CardiacDefects
Cardiacmalformationsarepresentintwo-thirdsofthepatients,andAVCDis
diagnosedinapproximately40%ofthecases,documentingastrongassociation
oftheatrioventricularseptaldefectwithterminaldeletionsof8p.34Ingeneral,
theAVCDiscompleteandoftenassociatedwithpulmonaryvalvestenosis.In
addition,thefindingofdextrocardia,abnormalitiesofthepulmonaryand
systemicvenousreturns,commonatrium,pulmonarystenosis,singleventricle,
andtranspositionofthegreatarteriesinanumberofpatientswithdeletion8p23
suggestthatcardiaclateralitydefectsmaybeinvolved.34–36
Nevertheless,thespectrumofCHDsinthissyndromeiswidebecause
conotruncalanomalies,ventricularoratrialseptaldefects,pulmonaryvalve
stenosis,andpatentductusarteriosushavebeenalsoreported36(seeTable77.4).
GeneticDefect
Thesyndromeisduetodeletionofthedistalpartofchromosome8p.35,37A
clusterofgenesaffectingheartdifferentiationislocatedonthedistal
chromosome8p.GATA4isconsideredacandidategeneforheartdefects
becauseitaffectstheinitialstepsofcardiacmorphogenesisandisfoundtobe
deletedinmajorityofpatientswithdeletion8pandCHD.38Nevertheless,itis
unclearatpresentifasinglegeneorseveralgenesinthisregionhavearolein
heartdifferentiation,andpositionaleffectscannotbeexcluded.36
MicrochromosomalAnomalies
Deletion22q11.2(Digeorge/Velocardiofacial
Syndrome)
ClinicalFeatures
Clinicalcharacteristicsofdeletion22q11.2includeCHD,palatalmalformations,
neonatalhypocalcemia,immunedeficit,speechandlearningdisabilities,facial
anomaliessuchashypertelorism,“hoodedeyelids,”tubularnose,smallmouthor
micrognathia,auricularabnormalities,andasymmetriccryingfacies(Fig.77.4
andTable77.5).39–41Palatalabnormalitiesarerepresentedbycleftpalate,
velopharyngealincompetence,submucosalcleftpalate,bifiduvula,and
functionalproblemssuchashypotoniaofthevelopharyngealmusculature.
Immunodeficiencyoccursasaresultofthymichypoplasia.Infact,impairedTcellproductionistheprimarydefectbecausetheroleofthethymusistosupport
thematurationofTcells.Hypocalcemiaistypicallymostrelevantinthe
neonatalperiodandissecondarytohypoparathyroidism.However,itmayrecur
inadulthood,especiallyconcomitantlywithbiologicstresssuchasfeveror
surgery.Developmentaldelayisexpressedasspeechdelay,intellectual
disability,andlearningdifficultiesinspecificareas.Psychiatricillnessand
predispositiontoschizophreniaarethemostcommongroupoflate-onset
conditionsinadolescentandadultpatients.42,43