Tải bản đầy đủ (.pdf) (3 trang)

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.



×