title: Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.
abstract: The congenital muscular dystrophies (CMDs) are a heterogeneous group of disorders. Among these, the laminin alpha 2 chain 'merosin' deficient CMD is caused 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 healthy parents. His motor and mental development were slow. Creatine kinase (CK) was elevated (2.100 U/l), and the muscle biopsy was dystrophic. He sat unsupported at 12 months and took his first steps at 3 years of age. At 6 years of age he could walk up to 500 m. He was mentally retarded and spoke single words only. At 1 year, MR imaging of the brain showed abnormal increased periventricular T2-signal, consistent with dysmyelination as well as pontocerebellar hypoplasia and several cerebellar cysts. The pattern of gyration was normal. Follow-up at 4 years showed normalization of the previously abnormal periventricular T2-signal. Immunohistochemical analysis of the skeletal muscle showed normal expression of laminin alpha 2 for a C-terminal antibody and antibodies to the 300 and 150 kDa fragments, as well as of laminins alpha 5, beta 1, beta 2 and gamma 1. The boy has two healthy younger brothers. Linkage analysis excluded the candidate loci on chromosomes 6q2 and 9q31. As such, the patient's data are suggestive of a new form of laminin alpha 2 positive CMD characterized by transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, University of Essen, Germany. thomas.voit@uni-essen.de
authors.forename: T
authors.initials: T
authors.lastname: Voit
authors.forename: R D
authors.initials: RD
authors.lastname: Cohn
authors.forename: J
authors.initials: J
authors.lastname: Sperner
authors.forename: B
authors.initials: B
authors.lastname: Leube
authors.forename: L
authors.initials: L
authors.lastname: Sorokin
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: R
authors.initials: R
authors.lastname: Herrmann
mesh_terms: D001706:Biopsy; D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000378:metabolism* / Q000473:pathology; D007797:Laminin / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008297:Male; D009136:Muscular Dystrophies / Q000151:congenital / Q000378:metabolism*; D009186:Myelin Sheath / Q000502:physiology*; D010375:Pedigree; D011149:Pons / Q000002:abnormalities*; D013997:Time Factors
chemical_list: D005819:Genetic Markers; D007797:Laminin