Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation

The congenital muscular dystrophies (CMDs) are a heterogeneous group of dis orders. Among these, the laminin alpha 2 chain 'merosin' deficient CMD is c aused by mutations of the LAMA2 gene on chr 6q2 and Fukuyama CMD is linked to chr 9q31. We report a 7-year-old boy who was born to consanguineous heal thy parents. His motor and mental development were slow. Creatine kinase (C K) was elevated (2.100 U/l), and the muscle biopsy was dystrophic. He sat u nsupported at 12 months and took his first steps at 3 years of age. At 6 ye ars of age he could walk up to 500 m. He was mentally retarded and spoke si ngle words only. At 1 year, MR imaging of the brain showed abnormal increas ed periventricular T2-signal, consistent with dysmyelination as well as pon tocerebellar hypoplasia and several cerebellar cysts. The pattern of gyrati on was normal. Follow-up at 4 years showed normalization of the previously abnormal periventricular T2-signal. Immunohistochemical analysis of the ske letal muscle showed normal expression of laminin alpha 2 for a C-terminal a ntibody and antibodies to the 300 and 150 kDa fragments, as well as of lami nins alpha 5, beta 1, beta 2 and gamma 1. The boy has two healthy younger b rothers. Linkage analysis excluded the candidate loci on chromosomes 6q2 an d 9q31. As such, the patient's data are suggestive of a new form of laminin alpha 2 positive CMD characterized by transient brain dysmyelination, pont ocerebellar hypoplasia and mental retardation. (C) 1999 Elsevier Science B. V. All rights reserved.