Long-term MRI and clinical follow-up of symptomatic and presymptomatic carriers of dysferlin gene mutations.

We report the results of a longitudinal study involving MRI and clinical follow-up in nine siblings from four families with Miyoshi myopathy (MM). All individuals carried pathogenic dysferlin gene (DYSF) mutations with six of them suffering from symptomatic disease and three being presymptomatic. In presymptomatic subjects, MRI was sensitive to detect alterations in muscle tissue years before disease onset. The first MRI alteration to disclose was evidence for myoedema in dorsal compartment muscles of the legs followed by fatty degeneration. Moreover, MRI changes anticipated the topography of subsequent clinical muscle involvement and progressed from distal to proximal dorsal leg muscles. In symptomatic subjects, MRI changes reflected the pattern and severity of clinical muscle involvement. MRI evidence, however, suggests that muscle involvement is much more prominent in early disease stages than clinically seen. Clinical follow-up up to 8 years made evident that MM onset occurs at a mean age of 18.4 years. The most prominent initial deficit was impaired tiptoe gait due to muscle plantarflexor dysfunction followed by impaired dorsiflexor function. Dorsal compartments were predominantly affected not only in distal but also in proximal leg muscles, and a more rapid progression was noticed during the early phase of the disease. Our data suggest that MRI is a helpful diagnostic tool for an early diagnosis of MM and other distal myopathies since it provides sensitive and topographic information about initial and even preclinical muscle involvement. This is of particular relevance in Miyoshi myopathy because distinct CK elevation is present long before its clinical onset and often misdiagnosed as "idiopathic".