engleski

Diagnostic dilemma in an atypical X-linked Emery-Dreifuss family

Emery-Dreifuss muscular dystrophy can be caused by mutations of X-linked EMD gene (XL-EDMD), and autosomal dominant LMNA gene (AD-EDMD). Aim. To report the phenotypic heterogeneity of XL-EDMD leading to diagnostic dilemma, especially when autosomal dominant transmission cannot be excluded because of affected females. Emphasis is made on the diagnostic value of extensive clinical, genetic and protein investigations. Patients and Methods. Ten members (6M/4F ; 4 affected, 4 non-affected and 2 inconclusive) of a five-generation Croatian family were assessed at neuro-muscular and cardiac levels. A large clinical and genetic survey was also indispensable. Western-blot analysis of emerin was performed on proband's lymphoblastoid cells. DHPLC/sequencing screened LMNA and EMD was sequenced. Results. The male proband presented as LGMD associated with calves hypertrophy, rigid spine and cardiomyopathy requiring pacemaker. His mother had moderate LGMD with neither cardiac involvement nor contractures. Proband's two sons, 11 and 12 year-old, had scapular winging. A maternal male cousin had moderate LGMD with contractures and pacemaker implanted in adulthood. AD-EDMD was suspected based on these data, but LMNA gene mutation was excluded. Further analysis of the pedigree showed that it could fit with X-linked inheritance: two maternal female cousins were asymptomatic, the son of one of them presented as severe EDMD since childhood, and a deceased maternal uncle had got pacemaker. The western blot found total absence of emerin in proband's sample. A large 142bp deletion in the EMD exon 1, removing the start and first codons, was characterized in 5 patients, confirming the diagnosis of XL-EDMD.

X-linked Emery-Dreifuss muscular dystrophy ; atypical ; diagnosis

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