Familial dilated cardiomyopathy secondary to dystrophin splice site mutation.
BACKGROUND
Idiopathic dilated cardiomyopathy (DCM) encompasses a heterogeneous group of disorders, posing significant diagnostic challenges. Genetic etiologies underlie an important subset of DCM, including 20 genes and 5 X-linked disorders to date. We report a family with a rare dystrophin gene alteration, identified after evaluation of asymptomatic children whose extended family history included cardiomyopathy, premature cardiac death, or cardiac transplantation.


RESULTS
Record review, clinical evaluations, and DNA samples were obtained from members of a 5-generation pedigree with early onset DCM. Five of 6 affected males experienced death or cardiac transplant in their second or third decades. No affected individuals had skeletal muscle weakness before acute cardiac decompensation. Dystrophin gene analysis of an affected family member revealed sequence alteration at the conserved 5' splice site of exon 1 of the muscle-specific isoform of dystrophin (IVS1 +1 G>T) and co-segregated with cardiac disease in this family.


CONCLUSIONS
Young males presenting with apparent isolated cardiomyopathy or acute myocarditis may harbor dystrophin mutations without overt skeletal muscle pathology. The etiology of familial risk was not evident in this pedigree before retrospective cardiovascular genetics assessment, highlighting ongoing diagnostic challenges and limitations of standardized screening panels (which do not include dystrophin) in patients with "idiopathic" DCM.
Obler
Dita
D
Department of Cardiology, Children's Hospital, Boston, MA 02115, USA. dita.obler.cgc@gmail.com
Wu
Bai-Lin
BL
Lip
Va
V
Estrella
Elicia
E
Keck
Sally
S
Haggan
Coral
C
Semigran
Marc
M
Smoot
Leslie B
LB
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002648:Child; D049029:Dystrophin-Associated Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011379:Prognosis; D012326:RNA Splicing / Q000235:genetics*; D018570:Risk Assessment; D015996:Survival Rate
D049029:Dystrophin-Associated Proteins