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ExtracardiacAnomalies
Isomerismisamultiorganissue.Assuch,anatomicandfunctionalanomalies
maybefoundinnearlyanyorgansystem.Thenumberoforgansystems,andthe
extenttowhicheachsystemisimpacted,ishighlyvariablefrompatientto
patient.

CentralNervousSystem
Anecroscopystudydemonstratedanatomiccentralnervoussystemanomaliesin
nearlyhalfofthosewithrightisomerism,albeitnoneofthepatientsinthis
particularserieswithleftisomerismhadcentralnervoussystemanomalies.48
Studiesinmicehavealsodemonstratedthatthosewithrightisomerismshowan
isomericarrangementofthesynapsesinthehippocampus.Whereasinthe
normalsituationsynapticarrangementdiffersinthetwohemispheresofthe
hippocampus,thesemicedemonstratedright-sidedsynapticarrangementinboth
hemispheres.71Centralnervoussystemanomaliesthatmaybepresentinclude
neuraltubedefects,corpuscallosumabnormalities,variouscranialdeformities,
andaqueductalstenosis.31,72–77Hydrocephalusmayalsobenotedinthosewith
isomerism.78Theprecisefunctionalimpactsofisomerismonthecentralnervous
systemhaveyettobedelineated.Whileitisunderstoodthatthosewith
congenitalheartdiseaseareathigherriskfordevelopmentaldelayand
behavioralissues,decreasedexecutivefunctioning,anddeficitsinattention,
whetherthereisanadditiveeffectduetoisomerismhasyettobe
determined.79,80

PulmonarySystem
Fromananatomicstandpoint,thepulmonarysystemisnearlyalwaysaffected.
Themostcommonanatomicanomalyinthepulmonarysysteminthosewith
isomerismisisomericarrangementofthebronchiandthelungsthemselves.As
describedearlierinthischapter,thosewithrightisomerismwillhaveshort,
eparterialbronchibilaterally,whilethosewithleftisomerismwillhavelong,
hyparterialbronchibilaterally.Additionally,thetracheobronchialangleinthose

withleftisomerismwillgenerallybelessthan135degreesbilaterallywhilein


thosewithrightisomerismitwillgenerallybegreaterthan135degrees.68–70
Therehavealsobeenthreeinstancesofamoreunusualbronchialarrangement
describedintheliterature.Inthesecasestherehavebeenatotaloffourbronchi
arisingfromthetracheadirectly.Inallthesecasesthetracheafirstgaverisetoa
pairofbronchi(onetotheleftandothertotherightlung)thatwereisomericin
appearancebutthetracheacontinuedinferiorlytoonceagaingiverisetoapair
ofbronchi(onetotheleftandothertotherightlung)thatwerealsoisomericin
appearance.48Thelungsthemselveswillalsodemonstrateisomerismina
majorityofpatientswithisomerism.Thosewithleftisomerismwilltendtohave
bilobedlungsbilaterallywhilethosewithrightisomerismwilltendtohave
trilobedlungsbilaterally.48,70
Functionalissueshavealsobeennotedinthepulmonarysystemofthosewith
isomerism.Whileboththosewithrightandleftisomerismtendtohave
increasedsinopulmonaryissuescomparedtothosewithoutisomerism,those
withleftisomerismaremorelikelytohaverecurrentupperrespiratory
infections,requirechronicpulmonologyfollow-up,andrequirehomeoxygen.81
Anecdotally,thosewithisomerismalsoappeartobemorelikelytohavegreater
chesttubedrainageandrequirelongerperiodsofpostoperativemechanical
ventilation.
Cardiopulmonaryexercisetestingdemonstratesthepresenceofboth
restrictiveandobstructivelungdiseaseinthosewithisomerism.Whilethe
etiologyoftherestrictivecomponentislikelyrepeatsternotomies,theetiology
oftheobstructivecomponenthasyettobedelineated.Cardiopulmonaryexercise
testingalsodemonstratesthatchildrenandadolescentswithisomerismdonot
tendtohaveimpairedexercisetolerancealthoughthismaybeduetoasurvival
andselectionbiasassome“sicker”isomerismpatientswilldieininfancy.In
addition,thosewithisomerismwhodosurvivetoanageappropriatefor

cardiopulmonaryexercisetestingmaybedeemedtooilltobeevaluatedby
cardiopulmonaryexercisetesting.82Thosewithisomerismarealsomoreprone
topulmonaryvasculardiseaseandpulmonaryhypertensionthanthosewithout
isomerism.Whileobjectivedatahavenotbeenpublishedtodocumentthisin
children,suchdatahavebeendocumentedinadultswithisomerism.Isomerism
inadultsindependentlyincreasedtheoddsofpulmonaryvasculardiseaseor
pulmonaryhypertensionby80%.Asthemechanismofthisincreaseisnotclear
atthispoint,itisalsonotpossibletocommentonspecifictherapeutic
interventionsinthisspecificpatientpopulation.83,84


GastrointestinalSystem
Asdiscussedpreviouslyinthischapter,abnormallateralizationoftheabdominal
organsiscommonlynotedinisomerism.Whilethisismostreadilyapparentin
thepositionofthestomachandliver,itmustbekeptinmindthatthegallbladder,
pancreas,andspleenarealsofrequentlyaffected.48Whendescribingthe
lateralityoftheabdominalorgans,theterm“situsambiguous”isnotahelpful
term.Thereis,infact,nothingambiguousaboutthelocationoftheorgans.The
sidednessofeachorganshouldbedescribedexplicitly.Othergastrointestinal
anomaliesthatmayoccurinthesettingofisomerismincludetracheoesophageal
fistula,congenitaldiaphragmatichernia,omphalocele,biliaryatresia,duodenal
atresia,pancreaticagenesis,analatresia,andAbernethymalformation.48,85–87
Eachoneofthoseanomaliesisnotedinlessthan10%ofisomerismpatients
whenstudiedindividually.
Inthesettingofisomerism,theintestinesarealsooftenabnormally
lateralized.Whatisuniquetotheintestinecomparedtotheotherabdominal
organsisthattheintestineswillremainpresentinbothhalvesoftheabdomen,
buttherotationwillbeabnormal.Indeed,aformofintestinalmalrotationmay
betheentireabsenceofrotationtobeginwith.Inthiseffect,thereisaspectrum
ofintestinalmalrotationthatmaybepresentinthechildrenwithandwithout

isomerism.Someformofintestinalmalrotationispresentinamajorityof
patients,withstudiesdemonstratingafrequencyof33%to90%dependingon
thespecificevaluationdone.88,89Whatisuniquetothosewithisomerism,
however,isthegreaterfrequencyofrotationalanomalieswithoutaparticularly
increasedriskofvolvulus.Thosewithisomerismandintestinalmalrotationhave
approximatelya1%frequencyofvolvulus.89–92Thosewiththeduodenojejunal
junctiononthecontralateralsideasthestomach,resultinginanarrow
mesentery,aremorelikelytoexperiencevolvulus.
Manycenterswillevaluateallisomerismpatientsforintestinalmalrotationvia
uppergastrointestinalstudies.Insomeofthesecenters,thosefoundtohaveany
anomalyofintestinalrotationwillundergoaprophylacticLaddprocedure.
Uppergastrointestinalstudieswillrequiresomecriticallyillinfantstobe
transportedtoradiologysuites,tasksthatcanbelaborintensiveandhighrisk.In
addition,theseproceduresareassociatedwithanadditionalcost.Furthermore,
asymptomaticpatientswhoarefoundtohaveintestinalmalrotationmayundergo
aprophylacticLaddprocedure,incurringmorecostandrisk.
Thisraisesthequestionofwhetherallinfantswithisomerismshouldbe