A SEVERE CLINICAL AND PATHOLOGICAL VARIANT OF CENTRAL CORE DISEASE WITH POSSIBLE AUTOSOMAL RECESSIVE INHERITANCE

Central core disease (CCD) is a well recognized, relatively mild, non- or slowly progressive, dominantly inherited, congenital myopathy due, at least in some families, to mutations in the ryanodine receptor gen e on chromosome 19q13.1. We report two unrelated cases with an unusual , early onset congenital myopathy with severe contractures, delayed mo tor milestones, proximal muscle weakness, normal serum creatine kinase (CK), a non-progressive course, with muscle biopsy findings of centra l cores and in addition, marked proliferation of connective and adipos e tissue, and variation in fibre size. Muscle biopsies from the parent s, who were non-consanguineous and healthy, showed minor myopathic cha nges and uneven staining with oxidative enzymes, but no central cores. The marked histological muscle changes, the distribution of weakness and the non-progressive course of the disease suggest that this is a s evere variant of central core disease with secondary dystrophy-like ch ange. The presence of mild changes in the histochemical reactions of b iopsies of both parents of these two children supports the hypothesis that they are carriers of a recessive disease gene mutation responsibl e for this unusually severe form of central core disease. (C) 1998 Els evier Science B.V. All rights reserved.