A severe clinical and pathological variant of central core disease with possible autosomal recessive inheritance

Abstract

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 gene on chromosome 19q13.1. We report two unrelated cases with an unusual, early onset congenital myopathy with severe contractures, delayed motor milestones, proximal muscle weakness, normal serum creatine kinase (CK), a non-progressive course, with muscle biopsy findings of central cores and in addition, marked proliferation of connective and adipose tissue, and variation in fibre size. Muscle biopsies from the parents, who were non-consanguineous and healthy, showed minor myopathic changes 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 severe variant of central core disease with secondary dystrophy-like change. The presence of mild changes in the histochemical reactions of biopsies of both parents of these two children supports the hypothesis that they are carriers of a recessive disease gene mutation responsible for this unusually severe form of central core disease.