Andersons pediatric cardiology 1654
Bạn đang xem bản rút gọn của tài liệu. Xem và tải ngay bản đầy đủ của tài liệu tại đây (126.78 KB, 3 trang )
FamilialDCMistypicallytransmittedinanautosomaldominantfashion,
althoughX-linkedandautosomalrecessivetransmissiondooccur,especiallyin
thesettingofneuromusculardisease.Itisworthnotingthatthefamilyhistory
aloneisinsufficientlysensitivetoassessthepossibilityoffamilialDCM.279
Furthermore,DCMshowsincompletepenetrance,age-relatedpenetrance,and
variableexpressivity,underscoringtheimportanceoflong-termscreeningand
monitoring,giventhecurrentyieldofgenetictesting.Thisisreflectedinthe
consensusstatementsregardingtheneedforlong-termscreening.
Anumberofmutationsincystoskeletal,nuclear,sarcomeric,ionchanneland
desmosomalproteinsmaycausedilatedcardiomyopathy(seeTable61.1).The
majorityofpatientswithapositivegenetictestwillhaveamutationintitin
(~20%ofpatients)withlessthan5%ofpatientshavingmutationsinothergenes
(mostcommonlyMYH7,LMNA,TNNT2,andTPM1).284,285Therelative
proportionofcaseswithpositivegenetestingandthefrequencyofmutation
withinspecificgenesappearstobedifferentinpediatricandadultdisease.Titin
appearstoagainharborthemostmutations,whereasthereappearstobea
concentrationofcasesduetoRNAbindingmotifprotein20RBM20in
children.285However,itisagainworthnotingthatthereclassificationof
pathogenicityiscommoninthecurrentera,andthustheyieldandfrequencyof
individualmutationsislikelytochangeovertime.
AsmallproportionofpatientswithfamilialDCMwillhaveX-linked
transmission.Themostcommoncausesareassociatedwithmusculardystrophy
(Duchenne,Becker,andEmery-Dreifussmusculardystrophies).286Rarecasesof
dystrophinopathyinfemaleshavebeenreported;however,themajorityof
carriersdonothavecardiacdiseaseuntilwellintoadulthood.287,288Barth
syndromeisanothercauseofX-linkedDCMduetomutationsintheTAZgene.
Itistypicallycharacterizedbyskeletalmyopathy,growthrestriction,
neutropenia,andDCM,althoughthereissignificantheterogeneityinthespecific
phenotype.289
Pathology
Grossly,DCMischaracterizedbyaglobularheartwithventricularcavity
enlargementaswellasdilationoftheatria(Fig.61.8).Thehearttypicallyhas
increasedoverallmassbutdecreasedwallthickness.290Microscopically,DCM
showsnonspecificpathologicfindingscharacterizedbyfiberhypertrophy,
myocytedegeneration,andinterstitialfibrosis.Theremaybeoccasionalfociof
inflammatorycellsaswell,althoughthecharacteristicsofinfiltratehelpto
distinguishDCMfromactivemyocarditis.291,292
FIG.61.8 Grosspathologicspecimenshowingconcentricleftventricular
hypertrophyinan8-week-oldinfantwithmitochondrialdisease.
Pathophysiology
Morethan50genesinmultiplesignalingpathwayshavebeenreportedtocause
DCM(seeTable61.1).282Mutationsinsarcomericproteinsaswellas
cytoskeletalandnuclearproteinsareassociatedwithDCM.282Althoughthe
molecularsignaturesmaybeunique(rangingfromabnormalforcegenerationto
abnormalitiesinmaintainingstructuralintegrityofthesarcomere),thefinal
phenotypicexpressionofdiseaseiscommonandnonspecific,featuringmyocyte
deathandfibrosis.
ClinicalFeatures
ThesymptomsofDCMaretypicallyagedependentandoftennonspecific.
Historically,approximately90%ofchildrenpresentwithsymptomsof
congestiveheartfailure,withonly5%presentingwithsuddendeath,3%
identifiedbyscreening,and2%duetoexerciseintoleranceor
arrhythmia.35,232,273,293,294
Symptoms
Respiratorysymptomsandfeedingintoleranceand/orfailuretothrivearethe
predominantsymptomsandpresentationamonginfants.Aspatientsbecome
progressivelyolder,theywillincreasinglyreportsubjectiveactivityintolerance
orshortnessofbreathonexertion;nonspecificgastrointestinalcomplaintsalso
persistaspatientsgetolder.
PhysicalExamination
Giventhatthemajorityofpediatricpatientsaresymptomaticatthetimeof
diagnosis,thephysicalexamistypicallyabnormal.Patients,especiallyinfants,
typicallypresentwithpersistentsinustachycardia,whereaspatientswithmore
advanceddiseasemaypresentwithweakpulses,pulsusalternans,and
hypotension.Isolatedatrialandventricularectopyiscommon,andconduction
abnormalitiesoratrial/ventriculartachycardiaraisethepossibilityofmyocarditis
orspecificgeneticdefects.Theapicalimpulseistypicallyprominentand
laterallydisplaced,andtheleftchestmaybedisproportionatelyprominentas
comparedwiththeright.Auscultationmayrevealagallopaswellasamurmur
consistentwithmitralregurgitation.
Respiratoryfindings,includingtachypneaandincreasedworkofbreathing,
maybefounduponpresentationinchildrenofallages.Wheezingandbasilar
cracklesmaybepresent,especiallyamonginfants;thismaydelaytheinitial
diagnosisduetoapresumptivediagnosisofreactiveairwaydiseaseor
bronchiolitis.
Jugularvenousdistentionisoftendifficulttoassessorevaluateintheinfant
butiscommonlypresentinallchildren.Hepatomegalyandelevationofliver
enzymesmayalsobepresentandreflectelevatedvenouspressures.Edemaof
theextremitiesandfaceandascitesmayalsobepresent.
Assessingmyotonia,musculartone,andbulkisimportantgiventhe
heterogeneouscausesofDCMinchildren,includingmitochondrialdiseaseand
neuromusculardisease.Itmaybedifficulttodistinguishinherentmuscle
weaknessfromchronicfailuretothriveoninitialpresentationandwithout
longitudinalexams.Abnormalophthalmologicorsensorineuraldeafnessmaybe
presentinmitochondrialdisease.Woollyhairandkeratodermamayoccurinthe
settingofcardiocutaneoussyndromes.
