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

Aim. To describe the clinical variability of X-linked Emery-Dreifuss muscul ar 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 carr ier. The Western blot analysis of emerin was performed on lymphoblastoid ce ll lines and followed by sequencing of the emerin gene. Results. A thymine insertion at nucleotide 417 in exon 2, resulting in a fr ameshift with a premature stop codon at position 62 and absence of function al protein, was found in one of the three available patients. In ten-year-o ld proband's dizygotic twin-nephews the intermittent first-degree A-V block , atrial and ventricular ectopy, atrial runs, and exit sinus block were fou nd, although the echocardiographic findings were normal. One of the twins a lso had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm. Conclusion. Cardiac abnormalities in the proband's ten-year-old dizygotic t wins without evident clinical features suggestive of EDMD were remarkable i n 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 muscl e 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 poss ibly preventive implications, It also points at genetic and environmental f actors as causes of clinical features in X-EDMD.