Congenital muscular dystrophy with primary laminin α2 (Merosin) deficiency presenting as inflammatory myopathy

Elena Pegoraro, Pedro Mancias, Steven H. Swerdlow, Radmila B. Raikow, Carlos Garcia, Harold Marks, Thomas Owen Crawford, Virginia Carver, Brad Di Cianno, Eric P. Hoffman

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Abstract

Ten laminin α2-deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin α2-deficient patients were carrying a diagnosis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin-deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10-kb laminin α2-coding sequence was screened for causative mutations by reverse transcriptase-polymerase chain reaction/single-stranded conformational polymorphism analysis in muscle biopsy specimens from 5 patients. Followed by automatic sequencing of aberrant conformers. Clear loss-of-function deletion mutations were identified in both alleles of 1 patient. Muscle histopathology in this patient showed a striking inflammatory infiltrate of T cells and B cells. Reexamination of biopsy specimens from other laminin α2-deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammatory process should be considered consistent with congenital muscular dystrophy.

Original languageEnglish (US)
Pages (from-to)782-791
Number of pages10
JournalAnnals of Neurology
Volume40
Issue number5
Publication statusPublished - Nov 1996

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pegoraro, E., Mancias, P., Swerdlow, S. H., Raikow, R. B., Garcia, C., Marks, H., ... Hoffman, E. P. (1996). Congenital muscular dystrophy with primary laminin α2 (Merosin) deficiency presenting as inflammatory myopathy. Annals of Neurology, 40(5), 782-791.