Résumé :
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Communication n° 520 Salih Congenital Muscular Dystrophy (Salih CMD) was described in 1998 in two brothers presenting with neonatal hypotonia, axial and proximal weakness and severe dilated cardiomyopathy leading to death in adolescence. The genetic defect remains unknown and no additional case has been reported yet. To better characterise this phenotype and its unknown genetic basis, we studied 8 patients from 4 families, including the original one. Clinical phenotype was evaluated retrospectively according to records and pictures. Muscle biopsies were reviewed, and complementary immunohistochemical and ultrastructural studies performed. Three families were consanguineous, suggesting an autosomal recessive transmission. All patients presented with early-onset, non- or slowly-progressive muscle weakness more marked in axial and facial muscles. Shoulder girdle amyotrophy contrasted with preserved quadriceps bulk and calf hypertrophy. All cases developed dilated cardiomyopathy from the ages of 4 to 15 years, leading to death in 7 of them between 8 and 19 years. Serum CK was normal or moderately elevated (2-6xN). Childhood muscle biopsies showed a myriad of centrally-located nuclei, predominance of type I fibres, irregular oxidative-negative areas, rare necrotic and regenerative fibres and mild endomysial fibrosis. Ultrastructural studies disclosed several foci of sarcomere disorganisation (minicores). Expression of dystrophin, a- and b-dystroglycan, sarcoglycans, laminin a-2 chain and integrin a-7 was normal. In the 3 consanguineous families, we excluded linkage to known candidate genes associated with muscle and heart disorders, including fukutin related protein (FKRP), cardiac b-myosin heavy chain (MYH7), lamin A/C (LMNA), selenoprotein N (SEPN1) and skeletal actin a-1 (ACTA1) genes. This work confirms the existence of a particular form of early-onset myopathy with severe cardiomyopathy, further delineates its phenotype and establishes its molecular individuality.
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