Congenital Muscular Dystrophy Type 1C

Abstract

MDC1C is a form of congenital muscular dystrophy with mental retardation and structural brain abnormalities and belongs to a group of disorders resulting from defective glycosylation of dystrophin-associated glycoprotein-1, collectively known as dystroglycanopathies. The clinical phenotype of four patients is characterized by onset at birth and inability to acquire independent ambulation. Other features included significant facial weakness, hypertrophy of the lower limb muscles, wasting of the shoulder girdle with pronation of the forearm, contractures of the Achilles tendon, and elevated CK. Muscle biopsies showed a severe decrease in alpha-dystroglycan and a mild secondary reduction in the laminin-alpha-2 chain (LAMA2). These findings suggested that the DAG1 protein is abnormally glycosylated in MDC1C and is central to the pathogenesis of the disorder. In seven families with MDC1C, the causative mutations were recognized to be the FKRP gene, encoding fukutin-related protein, a glycosyltransferase.