title: An early onset muscular dystrophy with diaphragmatic involvement, early respiratory failure and secondary alpha2 laminin deficiency unlinked to the LAMA2 locus on 6q22.
abstract: We present four subjects from one family and one subject (with an affected sibling who had died) from a second, unrelated family, with early onset, Duchenne-like, muscular dystrophy who presented with proximal girdle weakness, calf and generalized muscle hypertrophy, selective wasting of the sternomastoid muscles, rigidity of the spine and contractures of the tendo Achilles. Intellect was normal. Serum creatine kinase was grossly elevated and the muscle biopsies showed a dystrophic picture. All five subjects have developed early respiratory failure due to severe diaphragmatic involvement; two have already died aged 4 and 7 years of age and the remaining three are dependent on night time ventilation. There has been very little deterioration over time in the skeletal muscle function, and the survivors remain ambulant, the oldest being 11 years. Immunocytochemical studies of the muscle biopsy showed a normal pattern for dystrophin and the dystrophin-associated glycoproteins, but a reduction of the laminin alpha2 chain of merosin. Magnetic resonance imaging of the brain was normal. The disease did not link to the LAMA2 locus for laminin alpha2 on chromosome 6q, so that these families seem to represent a new form of autosomal recessive muscular dystrophy with a secondary merosin deficiency. The primary protein deficiency has not yet been identified.
authors.affiliation: Department of Paediatrics and Neonatal Medicine, MRC Clinical Sciences Centre Imperial College School of Medicine, Hammersmith Hospital, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: I
authors.initials: I
authors.lastname: Naom
authors.forename: V
authors.initials: V
authors.lastname: Dubowitz
mesh_terms: D000367:Age Factors; D001707:Biopsy, Needle; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003964:Diaphragm / Q000473:pathology*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D018392:Genomic Imprinting; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007150:Immunohistochemistry; D007797:Laminin / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012131:Respiratory Insufficiency / Q000235:genetics* / Q000473:pathology
chemical_list: D007797:Laminin