CONGENITAL MUSCULAR-DYSTROPHY ASSOCIATED WITH MEROSIN DEFICIENCY

''Classic'' congenital muscular dystrophy is a heterogeneous group of disorders, characterized by early-onset muscle weakness and hypotonia, absence of overt cerebral or ocular symptoms, and muscle pathology co nsistent with a dystrophic process. A subset of patients with congenit al muscular dystrophy have recently been found to be deficient in the extra-cellular matrix protein merosin. Consequently, we reviewed the c linical, pathologic, and immunohistochemical features of 12 patients ( six males and six females) with classic congenital muscular dystrophy who have been seen at the Children's Hospital, Boston, over the past 1 5 years. There was marked clinical heterogeneity within this patient p opulation, with age of independent ambulation ranging from 13 months t o 6 years. Immunocytochemical analysis using; antibodies to merosin, d ystrophin, 43-kDa dystroglycan, adhalin, and laminin was normal in 11 of 12 patients. One patient had markedly abnormal staining for merosin ; the majority of fibers were negative, although occasional fibers dem onstrated patchy staining. Immunoblot analysis in this patient demonst rated markedly reduced levels of merosin (< 10% compared to controls a nd other patients), of apparently normal size. Clinically this patient could be differentiated from the others by a marked elevation of seru m creatine kinase (> 1000 U/L) and the presence of early white-matter changes on magnetic resonance imaging. The results of this study suppo rt the observation that abnormalities of merosin are present in a subg roup of patients with classic congenital muscular dystrophy. Although marked elevation of serum creatine kinase and white-matter changes on magnetic resonance imaging may serve to distinguish these patients fro m other patients with congenital muscular dystrophy, there remains a l arge proportion of patients in whom the underlying pathogenesis remain s to be elucidated.