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

Neuromuscul Disord. 1999 Mar;9(2):95-101. doi: 10.1016/s0960-8966(98)00091-1.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Cerebellum / abnormalities*
  • Child
  • Genetic Linkage
  • Genetic Markers
  • Haplotypes
  • Humans
  • Intellectual Disability / metabolism*
  • Intellectual Disability / pathology
  • Laminin / analysis*
  • Magnetic Resonance Imaging
  • Male
  • Muscular Dystrophies / congenital
  • Muscular Dystrophies / metabolism*
  • Myelin Sheath / physiology*
  • Pedigree
  • Pons / abnormalities*
  • Time Factors

Substances

  • Genetic Markers
  • Laminin