Table77.2
PrevalenceofClinicalFeaturesinPatientsWithDownSyndrome
ClinicalFeature
Developmentaldelay
Facialanomalies
Congenitalheartdefect
Atrioventricularcanaldefect
Ventricularseptaldefect,inlettype
Atrialseptaldefect
TetralogyofFallot
Other
Duodenalatresia
Hirschsprungdisease
Analatresiaorstenosis
Ocularanomalies
Frequency(%)
100
100
50
40
25
20
10
5
20
10
8
5
CardiacDefects
CHDsarediagnosedinapproximately50%ofpatientsbuttheincidenceislower
inthosewithtrisomy21mosaicism.13Theclassicstudiesreportedthatthemore
frequentcardiacdefectisAVCD,followedbyatrialseptaldefects,ventricular
septaldefects,andtetralogyofFallot(seeTable77.2).14However,inAsianand
NativeAmericanchildrenwithDownsyndrometheprevalenceofvarioustypes
ofcardiacdefectisquitedifferentincomparisonwiththewhitepopulation.The
mostcommoncardiacdefectinAsianandNativeAmericanchildrenwithDown
syndromeissimilarfromageneticpointofview15andistheventricularseptal
defectfollowedbytheAVCDthatisprevalentinwhites.14Thisfinding
suggestedthat,inpersonswithDownsyndrome,othergeneticfactors(different
fromtrisomy21)maybeinvolvedinthepathogenesisofthevarioustypesof
CHD.
SomeanatomicpatternsofCHDarequitedistinctinthecondition.In
particular,thecompleteformofAVCD,whichisprevalentinDownsyndrome,
israrelyassociatedwithothercardiacanomalies,excludingtetralogyofFallot.
Particularly,left-sidedobstructivelesions,includingrightventriculardominance,
subaorticstenosis,andaorticcoarctation,arerare,incontrasttotheAVCD
patientswithnormalkaryotype.Anomaliesofthevisceralsitus,ventricularloop,
andtranspositionofthegreatarteriesarevirtuallyabsentinthesepatients.16
Theinlettypeventricularseptaldefect(VSD)isprevalentinpatientswith
Downsyndrome,whereasmuscularandsubarterialseptaldefectsareveryrare.17
Amajorimpactincardiologicmedicalandsurgicalmanagementofpatients
withDownsyndromeisduetotheobservedfavorableanatomiccharacteristics
oftheheart.Infact,surgicalresultsofboththepartialandthecompletetype
AVCDarebetterinpatientswithDownsyndromecomparedwithnonsyndromic
children,withtheexceptionfortheknowntendencytodeveloppulmonary
hypertensioninDownsyndrome.18Downsyndromehasbeenidentifiedasthe
mostsignificantriskfactorforatrioventricularblockaftersurgicalclosureof
perimembranousVSD,andthisshouldbeexplainedconsideringtheprevalence
ofinletextensionofthemalformation.
ParticularattentionintheperioperativeperiodinDownsyndromepatients
shouldbeaddressedtotheassociatednoncardiacissues,suchasrespiratory
obstructivedisease,immunesystemdisorders,andinfections.
GeneticDefect
Downsyndromeiscausedbytrisomyofchromosome21.Theoverexpressionof
genesmappingonthischromosomeshouldbeconsideredrelatedtotheetiology
ofmalformationsanddevelopmentaldelayinDownsyndrome,althoughthe
molecularbasisregulatingthepresenceandanatomyofCHDisstillunclear.
AcriticalregionforCHDhasbeenidentifiedonchromosome21,butvariants
ingenesmappingondifferentchromosomeshavealsobeenconsideredtobe
etiologicallyinvolved,suchasCRELD1,FBLN2,FRZB,andGATA5.19In
addition,apotentialroleofcopynumbervariationsmappingonchromosomes
differentfromthe21hasbeenevidencedinthepathogenesisofCHDinDown
syndrome.20Thesegeneticvariantsmayexplainthevariabilityofcardiac
phenotypeandtheethnicdifferences.
SomerecentobservationsinmousemodelshavepointedtoaroleoftheShh
signalingpathwayinDownsyndrome.Cerebral,skin,liver,andintestinemice
trisomiccellshaveshowndefectivemitogenicShhactivitywithcell
proliferationimpairmentduetoahigherexpressionofPtch1,areceptor
normallyrepressingtheShhpathway.21Inaddition,subcutaneousadministration
oftheShhpathwayagonistSAGtotrisomicTs65Dnmiceatbirthresultedinan
increasedproliferationofgranulecellprecursorsinthecerebellum.22
TurnerSyndrome
ClinicalFeatures
Clinicalcharacteristicsincludeshortstature,gonadaldysgenesis,CHD,renal
malformation,pectusexcavatum,cubitusvalgum,pterygiumcolli,lymphedema,
andfacialanomalies,includingpalpebralptosiswithelongatedfissures,
epicanthalfolds,flatnasalbridge,anddownturnedmouth(Table77.3andFig.
77.2).23MostpatientswithTurnersyndromehaveintelligencefallingwithinthe
normalrange.Thephenotypeishighlyvariablebetweenaffectedsubjects.
Table77.3
PrevalenceofClinicalFeaturesinPatientsWithTurnerSyndrome
ClinicalFeature
Shortstature
Gonadaldysgenesis
Pterygiumcolli/Shortneck
Facialanomalies
Lymphaticanomalies
Skeletalanomalies
Hypertension
Renalanomalies
Congenitalheartdefect(45,Xkaryotype)
Aorticcoarctationalone
Bicuspidaorticvalvealone
Aorticcoarctationandothercardiovascularanomalies
Aorticvalvestenosis
Hypoplasticleftheartsyndrome
Anomalouspulmonaryvenousreturn
Other
Conductiveorsensorineuraldeafness
Developmentaldelay
Frequency(%)
95
95
80
75
60
50
45
25–45
25–40
25
25
10
10
5
5
20
25
3