Andersons pediatric cardiology 693
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variationseeninventricularmorphology.Itisnotclearwhyisomerismofthe
rightappendagesshouldmorefrequentlybeassociatedwithauniventricular
atrioventricularconnectionorwitheitherpulmonaryatresiaorstenosis.
Genetics
Theprecisegeneticsofisomerismarestillbeingdelineated.Whatisinteresting
tonoteisthatstudiesinmicedemonstratethatknockoutofthesamegenewill
leadtoasimilarresultinatrialappendagemorphology,whereassplenic
morphologycanvary.Thisfurtherimpliesthatdescribingthisclinicalentityas
isomerismsegregatedbyatrialappendagemorphologyismoreappropriateand
helpfulthandescribingthisclinicalentityasheterotaxysegregatedbysplenic
morphology.Severalgeneshavebeenimplicatedinbeingassociatedwith
isomerism.Atleast20%to30%ofpatientswillhaveamutationinoneofthese
genes.IsomerismhasbeendescribedtohaveX-linkedinheritance,autosomal
dominantinheritancewithreducedpenetrance,andautosomalrecessive
inheritance.129Todate,morethan100geneshavebeenimplicatedinmicewith
isomerism,althoughonlyaproportionofthesearealsoimplicatedinhumans.
Studiesinhumanshavebeenlimitedtosmallerstudiesthatareoftencase
reports.Thereforemoredataareneededovertimetomakeconclusions
regardingthegeneticmechanismsofisomerisminhumans.130Genesthathave
beenrepeatedlynotedtobeaffectedinhumanswithisomerismincludeNodal,
Shh,ZIC3,PITX2,LeftyA,andLeftyB.GenesintheACVR,CCDC,CFC,
DNAAF,DNAH,DANI,FOXH1,andNKXfamilieshavealsobeen
implicated.131–143Recentdatahavedemonstratedthatcertaingenesbeing
affectedmayleadtosimilarphenotypesinpatients.Somegenesaremorelikely
tobeaffectedinthosewithrightisomerism,whereasothersaremorelikelytobe
affectedinthosewithleftisomerism.Theclinicalcoursealsoappearstodiffer
withdifferentaffectedgenes,likelyduetounderlyingseverityofdisease.144
ClinicalConsiderations
Througheducationandadvocacy,cliniciansareableproperlytopreparepatients
andfamiliesofthenuancescommonlyassociatedwithisomerism.Asmentioned
previously,bothleftandrightisomerisminvolvevaryingtypesofcardiacdefects
thatwillrequiresurgicalinterventionduringtheearlystagesoflife.Depending
ontheseverity,childrenmayhavemultiorgansysteminvolvementwithpotential
tobecriticallyill.Childrenmayrequireprolongedhospitalizations,specifically
inanintensivecareunit,whichcaninvolveavarietyofspecialtiessuchas
gastroenterology,pulmonology,andcardiology.Alongwiththeinitialdiagnosis
ofisomerism,theinpatientandoutpatientexperiencespatientsandfamilieswill
endurearelikelytocreatefeelingsofstress,fear,anxiety,andhelplessness.
Clinicalconsiderationsforthispatientpopulationshouldfocusprimarilyon
familyeducation,patientoutcomes,andpatientadvocacy.
Childrenwithisomerismwhoundergomultiplesurgicalinterventionsand
extendedhospitalizationsareatanincreasedriskforlong-termcomplications
suchaspulmonaryhypertension,arrhythmias,neurodevelopmentaldelays,and
mostimportantlybacteremia.Familyeducationistheutmostimportant
considerationbecauseitpromotesearlyidentification,immediatemanagement,
andbestpatientoutcomes.Familiesshouldbecounseledonwhatmayoccur
duringtheinpatienthospitalizationaswellonwhatmayoccurintheoutpatient
setting.Symptomsthatshouldpromptmedicalevaluationasanoutpatientmust
specificallybereviewedwithpatientsandtheirfamilies.Forexample,toreduce
theincidenceofbacteremia,parentsandfamiliesshouldunderstandthe
importanceofgoodhandwashingtechniques,diligentoralhygiene,including
dailycareandregulardentalvisits,andtheneedtoavoidillpersons.Itiscrucial
forparentstoadheretotheadministrationofdailyantibioticprophylaxisand
vaccinations.Amedicalmanagementplanshouldbedevelopedandfollowed
diligentlyamongfamilymembersandschoolpersonnelifapplicable.Schoolagedchildrenshouldwearamedicalbraceletatalltimes.Theclinicianshould
highlightthattheseinfectionrisksarelifelongandcontinueintoadulthood.If
complicationsoccurandhospitalizationisrequired,itisnotuncommonfor
familiestoexperiencebothphysicalandemotionaldifficulties.Cliniciansmust
beskilledinassessingthefamily'sunderstandingofthestatus,treatmentplan,
andprognosisforthechild.Theyshouldassistwithcoordinationofcareand
facilitateestablishmentofreasonablegoalsandexpectationsforboththefamily
