CONGENITAL MUSCULAR-DYSTROPHY WITH PRIMARY LAMININ ALPHA-2 (MEROSIN) DEFICIENCY PRESENTING AS INFLAMMATORY MYOPATHY

Ten laminin alpha 2-deficient patients were identified by both immunof luorescence and immunoblotting (30% of congenital muscular dystrophy p atients tested). Three of the laminin alpha 2-deficient patients were carrying a diagnosis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin-deficient patients w ere 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 alpha 2-co ding sequence was screened for causative mutations by reverse transcri ptase-polymerase chain reaction/single-stranded conformational polymor phism analysis in muscle biopsy specimens from 5 patients, followed by automatic sequencing of aberrant conformers. Clear loss-of-function d eletion mutations were identified in both alleles of 1 patient. Muscle histopathology in this patient showed a striking inflammatory infiltr ate of T cells and B cells. Reexamination of biopsy specimens from oth er laminin alpha 2-deficient patients showed minor signs of inflammati on in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis mode l for this major subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammato ry process should be considered consistent with congenital muscular dy strophy.