Résumé :
|
Communication n° 316 Introduction : Mutations in myotilin have been previously associated with limb girdle muscular dystrophy type 1A and a subgroup of myofibrillar myopathy. Objective : To analyze clinical/pathological manifestations associated with myotilin mutations in a group of newly identified Spanish patients and define the phenotypic spectrum of myotilinopathies. Methods : Five patients from two unrelated kindreds and six patients without family history of disease carrying myotilin mutations have been identified. Periodic clinical exams were performed in each patient and muscle biopsy in nine. Results : The disease is characterized by the onset at the age of 42 to 77 years with muscle weakness initially in distal and sometimes proximal leg muscles, eventually spreading to other muscle groups of the lower and upper extremities, and associated signs of cardiomyopathy, respiratory failure and peripheral neuropathy in the minority of cases. Focal myofibrillar destruction resulting in intracytoplasmic deposits strongly immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemmally located non-rimmed vacuoles and streaming Z-lines - allow to establish continuum between our observations and previously reported cases and define diagnostic limits of myotilinopathy. Conclusion : Clinical/myopathological studies of Spanish patients with myopathy associated with myotilin mutations and comparison to previously reported cases establish a continuum of phenotypic manifestations characteristic of myotilinopathies, an emerging neuromuscular disorder.
|