title: Apical hypertrophic cardiomyopathy due to a de novo mutation Arg719Trp of the beta-myosin heavy chain gene and cardiac arrest in childhood. A case report and family study.
abstract: Hypertrophic cardiomyopathy (HCM) is a myocardial disease with variable phenotpye and genotype. To demonstrate that the mutation Arg719Trp in the cardiac beta-myosin heavy chain (beta MHC) gene is a high risk factor for sudden death and can be associated with an unusual apical non-obstructive HCM, we report the case of a 6 1/2 year old boy, who suffered cardiac arrest. The proband had a de novo mutation of the beta MHC gene (Arg719Trp) on the paternal beta MHC allele and a second maternally transmitted mutation (Met349Thr), as was shown previously (Jeschke et al. 1998 (11)). Here we report the clinical phenotype of the proband and of his relatives in detail. The proband had a marked apical and midventricular hypertrophy of the left and right ventricle without obstruction. There was an abnormal relaxation of both ventricles. Holter monitoring detected no arrhythmia. Ventricular fibrillation was inducible only by aggressive programmed stimulation. The boy died 3 1/2 years later after another cardiac arrest due to arrhythmia. Five carriers of the Met349Thr mutation in the family were asymptomatic and had no echocardiographic changes in the heart, suggesting a neutral inherited polymorphism or a recessive mutation. It is concluded that there is an association of the mutation Arg719Trp in the beta-myosin heavy chain with sudden cardiac death in a young child. Disease history in conjunction with the genetic analysis suggests that the implantation of a defibrillator converter would have been a beneficial and probably life saving measure.
authors.affiliation: Universitätskinderklinik der LMU-Kardiologie, München, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Döhlemann
authors.forename: J
authors.initials: J
authors.lastname: Hebe
authors.forename: T
authors.initials: T
authors.lastname: Meitinger
authors.forename: H P
authors.initials: HP
authors.lastname: Vosberg
mesh_terms: D001120:Arginine / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D003062:Codon / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004452:Echocardiography; D004562:Electrocardiography; D004594:Electrophysiology; D006801:Humans; D008297:Male; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014364:Tryptophan / Q000235:genetics
chemical_list: D003062:Codon; D014364:Tryptophan; D001120:Arginine; D018995:Myosin Heavy Chains