Andersons pediatric cardiology 1566

Myocardialinvolvementisverycommon.Itisuncertainatwhatstageit
begins,sincethephysicalincapacitylimitsitsmanifestation.Theheartcanbe
involvedfromanearlyage,though,andinambulatorypatients,subclinical
diseasemaybecomesymptomaticwithexercise.Innonambulatorypatients,a
restingtachycardia,224decreasedheartratevariability,225echocardiographic
evidenceofsystolicanddiastolicdysfunction,226andabnormalmyocardial
strainchangesonmagneticresonanceimaging227mayhelptoalerttheclinician
tosubclinicalmyocardialinvolvementsothatmedicaltherapycanbeinitiated.
Therolesofcardiactroponinsandbrainnatriureticpeptidearealsobeing
evaluatedintheassessmentofthesepatients.228Thecardiacdysfunctionis
progressive,ultimatelyresultinginadilatedcardiomyopathy,andthebenefitsof
earlymedicaltherapyarecontroversial.Someadvocateearlyuseofafterload
reductiontherapy,229,230butothershaveonlyshownabenefitwhenafterload
reductioniscombinedwithβblockade.231
ThereisadistinctiveECGpatternin50%to90%ofpatients.Thisincludes
tallRwavesovertherightprecordialleadswithincreasedR:Samplituderatios,
togetherwithnarrowanddeepQwavesinthelimbandleftprecordialleads.
FemalecarriersmayalsohaveanabnormalECG.232Thesefindingscorrespond
topathologicobservations.Thereisfattyandfibroustissuereplacementofthe
myocardiumwithselectivescarringoftheposterolateralwalloftheleftventricle
and,sometimes,involvementoftheposterolateralpapillarymuscle.Conduction
abnormalitiesarealsofrequentlyseen.Amongtheseareprolongedintra-atrial
conduction,rightbundlebranchblock,asuperiorQRSaxis,andashortPR
interval.Histologicstudiesoftheconductionsystemshowareasoffibrosis,
vacuolization,andfattyinfiltration.233Theechocardiogramrevealsimpairment
ofbothsystolicanddiastolicfunction.Thicknessoftheleftventricularwallis
decreased,andthisisnotrelatedtophysicalinactivity.Theend-diastolicand
end-systolicdimensionsoftheleftventricleincreaseassystolicfunction
deteriorates.
Thediagnosisismadefromtheclinicalcharacteristics,thehighlevelsof
creatinekinaseactivity,andbiopsyoftheskeletalmuscles.Creatinekinase

activityis100to300timesnormalat1to5yearsofage.Othermuscleenzymes
—suchasaldolase,glutamicoxalictransaminase,lacticdehydrogenase,and
pyruvatekinase—arealsogrosslyelevated.Creatinekinaselevelsdiminishlater
inthediseasebutstillremainwellabovenormallimits.Musclebiopsyshows
scatteredhyalinefiberswithactivemusclenecrosisandregeneration.Thereis


splittingofthemusclefiberswithfattyreplacement.Themusclefasciclesalso
becomesurroundedbyperimysialandendomysialconnectivetissue.
Electromyographyrevealsadecreaseinthemeanactionpotentialvoltageandits
duration.Anincreaseinthenumberofpolyphasicpotentialsisalsoseen.
Carefulgeneralmedicalmanagementiscritical.Sincebedrestisharmful,
regularphysicalactivityandexercisearetobeencouraged.Avoidanceofobesity
isanimportantgeneralmeasure,alongwiththepreventionofmuscle
contracturesbypassivestretching.Becauseoftherisksofanesthesiaand
immobilization,thebenefitfrommajororthopedicproceduresmustbecarefully
considered.Preventionofscoliosisandthoracicdeformitiesinthewheelchair
phasehelptoavoidrespiratoryimpairmentandslowthedeteriorationof
respiratoryfunction.Deathisusuallyfromrespiratoryinfectionsand
insufficiency,heartfailure,orcardiacarrhythmias.Detectionofcarriersis
importantforappropriategeneticcounseling.Overhalfthecarrierscanbe
identifiedbytheirelevatedcreatinekinaselevels,electromyography,andmuscle
biopsy.Theanalysisofthepedigreeisparticularlyuseful.
Noveltreatmentsforthismyopathyareactivelybeinginvestigatedand
includegenetherapy,234proteaseinhibitors,235membranestabilizers,236and
muscleprecursorcelltransplantation.237

ChildhoodLimb-GirdleMuscularDystrophy
Thechildhoodlimb-girdlemusculardystrophies(LGMDs)areaheterogeneous
groupofgeneticmusculardisorders.Atleast17differenttypeshavebeen

described.Theycanbeinheritedineitheranautosomaldominantorrecessive
fashion.Sevengeneticdefectshavebeenidentifiedinthedominantforms
(LGMD1)and11intherecessiveforms(LGMD2).Theageatonsetis
variable,butsymptomsgenerallyappearbetween5and10yearsofage.
Weaknessofthepelvicandshouldermusclespredominates.Thediseaseis
slowlyprogressive,andthepatientsoftenbecomeunabletowalkbytheir
twenties.
Thediseaseisfirstsuspectedwhenlimb-girdleweaknessoccurs,although
DuchenneorBeckermusculardystrophymustberuledout.Anelevatedcreatine
kinasewillnotdifferentiatebetweenLGMDandthedystrophinopathies.This
canbedonethroughanalysisofthedystrophingeneandbyexaminationofa
musclebiopsy.
VariousformsofLGMDaffecttheheart.PatientswithLGMD1b,duetoa


mutationinthelaminA/Cgene,frequentlydeveloparrhythmiasthatcanbe
lethalandmayrequireplacementofanimplantabledefibrillator.Atrioventricular
blockcanalsooccur,necessitatingplacementofapacemaker.238Thisdisorder
canalsoresultinadilatedcardiomyopathy.
PatientswithLGMD2I,causedbyadefectinthegeneencodingthefukutinrelatedprotein(FKRP),maydevelopadilatedcardiomyopathybythethird
decade.Evidenceofdysrhythmiasisnotseen.239

MyotonicMuscularDystrophy(SteinertDisease)
Theinvolvementofsystemictissuestogetherwiththepresenceofmyotoniaand
muscularatrophyseparatemyotonicmusculardystrophyfromtheother
musculardystrophies.Myotonicmusculardystrophyhasahighincidence,
calculatedat13.5per100,000livebirths.Onsetisusuallybetween20and50
yearsofage,butmanycasesareclinicallyapparentduringchildhood.This
diseaseisduetoanexpansionofaCTGtrinucleotiderepeatontheqarmof
chromosome19.240Itistransmittedinanautosomaldominantfashionand

demonstratesgeneticanticipation.
Myotoniaisthepresentingclinicalfeatureinone-thirdofcases.Others
presentwithweaknessofthehands,footdrop,oratendencytofall.Theheart
mayoccasionallybecomeinvolvedpriortodiagnosisoftheneuromuscular
disorder.Thefacial,masticatory,sternomastoid,forearm,anteriortibial,and
peronealmusclesarethosefirstaffectedbyweakness.Laterweaknessextendsto
neighboringmusclegroups.Thetypicalfaciesarecharacterizedbylackoffacial
expressionanddifficultyinclosingtheeyesandmovingthemouth.Ptosisand
dysarthriaarefrequent.Myotoniaisoftenlimitedtothetongue,forearms,and
hands,butitmaybegeneralized.Thetendonreflexesintheaffectedmuscle
groupsarereduced.
Cataractsarepresentinalmostallthoseaffected.Impairedpulmonaryvital
capacityandmaximumbreathingcapacityarecommon.Abnormalcontractions
oftheesophagusarethoughttobethecauseofdysphagiaandpulmonary
aspiration.Testicularatrophy,DM,increasedmetabolismofimmunoglobinG
withlowserumlevels,progressivedementia,andsubnormalintelligenceare
frequentassociations.Cardiacinvolvementiscommonandmanifestswith
conductiondefectsandarrhythmias.First-degreeatrioventricularblockis
commonlyseen,andthismayprogresstocompleteheartblockrequiring
pacemakerimplantation.241Norelationshipexistsbetweenthedegreeof