Congenital muscular dystrophy

Congenital muscular dystrophy (CMD) falls into two major categories: the classical (Occidental) form with no apparent CNS involvement and the Fukuyama type (FCMD) with significant CNS manifestations. The recent discovery of merosin deficiency leads the classical form to subclassify to the merosin-positive and merosin-negative forms. ^[1] The merosin-negative form has relatively homogeneous clinical and pathologic features, with marked motor disability and normal mentality, but with areas with low signal intensity on MRI and decreased attenuation on CTs, as well as relatively high CK levels. ^[2] This disease is linked to chromosome 6q22-23, ^[3] a merosin coding region, and appears to be a single disease entity.

We performed this study to characterize the merosin-positive form of CMD (MP-CMD) clinically and pathologically. We selected patients with the Occidental, non-FCMD, who fulfilled the following diagnostic criteria: (1) muscle weakness and hypotonia during early infancy, delayed developmental milestones, or apparent muscle weakness when they began to walk, (2) no CNS symptoms except for mild mental retardation, (3) no brain CT/MRI abnormalities except for white matter lucency, (4) muscle findings consisting of necrotic and regenerating processes, (5) normal immunohistochemistry and immunoblotting to antibodies to dystrophin and dystrophin-associated glycoproteins. We applied an antimerosin antibody to the muscle biopsy specimens to subdivide these patients into the merosin-positive and merosin-negative groups.

Methods.

From the 4,434 muscle biopsy specimens examined in our laboratory from 1978 to 1993, we selected patients with MP-CMD based on both clinical and pathologic findings. Questionnaires were sent to their attending physicians to learn the present status of these patients and their laboratory findings. We examined seven patients personally at the time of muscle biopsy and followed them for 4 to 14 years. We evaluated the following clinical features: age at onset of symptoms, motor milestones, maximal motor function achieved, progression of muscle weakness, intelligence, nonmuscular …