Muscular dystrophy due to dysferlin deficiency in Libyan Jews - Clinical and genetic features

The cluster in Jews of Libyan origin of limb-girdle muscular dystrophy type 2B due to a dysferlin 1624delG mutation is described. The carrier frequenc y of this mutation is calculated to be similar to 10% in this population, i n which the disease prevalence is at least 1 per 1300 adults. Twenty-nine p atients from 12 families were all homozygous for the same mutation. However , clinical features were heterogeneous even within the same family: in half of the patients onset was in the distal muscles of the legs, which is simi lar to Miyoshi myopathy, while in others onset was in the proximal musculat ure, which is similar to other forms of limb-girdle dystrophies. Age at ons et varied from 12 to 28 years (mean 20.3 +/- 5.5 years), One patient was pr esymptomatic at age 28 years. Progression was slow regardless of age of ons et, patients remaining ambulatory until at least 33 years, Five patients de scribed subacute, painful enlarged calves as an early, unusual feature. The variable features in this ethnic cluster contribute to the definition of t he clinical spectrum of dysferlinopathies in general, The cause of the obse rved heterogeneity remains unclear.