Clinical variability and molecular diagnosis in a four-generation family with X-linked Emery-Dreifuss muscular dystrophy

Abstract

Aim: To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in the STA gene.

Methods: Clinical data were provided for 4 affected males and a female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene.

Results: A thymine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of the three available patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm.

Conclusion: Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without a pacemaker, and to the proband who had a very early onset of muscle wasting and weakness, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T) has practical early diagnostic and possibly preventive implications. It also points at genetic and environmental factors as causes of clinical features in X-EDMD.