X-linked Emery-Dreifuss muscular dystrophy: a multicenter, Italian, cohort study

X-linked Emery-Dreifuss muscular dystrophy (EDMD1) is a rare early-onset myopathy, affecting 1/400.000 individuals, characterized by humeroperoneal weakness, contractures and cardiac involvement. EDMD1 natural history has been poorly investigated, with most of the studies including only a few patients. The aim of the study was to investigate the clinical and molecular features in a large Italian cohort of EDMD1.

We retrospectively collected data of 38 genetically defined EDMD1 males (16 members of 6 families, and 22 sporadic cases) and 10 female carriers, from 14 referral neuromuscular centers in Italy. Patients were included only if showing detectable muscle weakness or contractures at the neurological examination.

Mean age at onset of patients was 12.0 ± 3.4 years (range 2-61). Among them 32 (84.2%) presented with muscle weakness or contractures and 6 (15.8%) with cardiac symptoms. Twenty-nine (76.3%) patients had heart involvement, with a mean age at onset of 24.2 ± 13.1 years. Age at disease onset was significantly different (p = 0.0011) between patients with cardiac onset and those with muscular onset. Moreover, patients with muscular onset had worse (p = 0.0163) motor performance at last follow-up (LFU), according to Gardner-Medwin-Walton Scale (GMWS). Loss of walking ability was observed in 3/38 (7.9%) patients, after a disease duration of 35, 49 and 35 years, respectively. Most of the remaining patients showed a mild disease severity, scoring 1-3 at the GMWS at LFU. Ten EMD mutations were novel and unreported in the literature.

Our data provide further insight in the field of EDMD1 and suggest that the disease natural history is dominated by heart involvement, while skeletal muscle weakness slowly progresses over the years.