Dysferlinopathy (LGMD2B): a 23-year follow-up study of 10 patients homozygous for the same frameshifting dysferlin mutations

The limb-girdle muscular dystrophies are a group of inherited neuromuscular disorders which are clinically and genetically heterogeneous. We have been able to carry out a follow-up study on 10 patients from a large Palestinia n family with a confirmed mutation in the dysferlin gene. These patients ha ve been followed for more than 23 years since the onset of the disease. The y all had normal developmental milestones. The onset of the disease was usu ally in the second decade, more rarely in the third and fourth decades. The first symptoms were difficulty with running and climbing stairs. Patients showed a distinct type of gait due to the unique pattern of muscle involvem ent which was characterised by early involvement of the posterior muscle co mpartment of the thighs and legs (hamstrings, adductors, gastrocnemius and soleus). The shoulder and upper limb musculature became involved later, esp ecially supra and infraspinatus and biceps. In the early stages of disease these patients may clinically show only proximal lower Limb-girdle muscle w eakness; however, the use of muscle imaging techniques were very important, always detecting in these patients also distal lower limb muscle involveme nt, so that the pattern of muscle involvement found in dysferlin deficiency may not strictly conform to the definition of limb-girdle muscular dystrop hy. The pattern of muscular dystrophy is essentially uniform and has clearl y distinct features (involving mainly the initial pattern of muscle involve ment and the mode of gait) which differ significantly from the well reporte d clinical features associated with sarcoglycanopathy, calpainopathy and Mi yoshi myopathy. (C) 2001 Elsevier Science B.V. All rights reserved.