P.179European collaboration on clinical and genetic heterogeneity of sarcoglycanopathies

Abstract

Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutation in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with sarcoglyconopathies created a European network. The aim of this study in to determine the clinical and genetic spectrum of a large cohort of European patients with sarcoglycanopathy from this European network. A total of 32 neuromuscular centers agreed to establish a European network on sarcoglycanopathies. Eleven 11 of them have provided patients demographic, genetic and clinical data. A total of 127 patients were collected, of which 49 had a confirmed diagnosis of LGMDR3, 15 of LGMDR4, 58 of LGMDR5 and 5 of LGMDR6. Thirteen patients were reported as asymptomatic. The global mean age at symptoms onset was 7.9 years, being LGMDR5 the disease with earliest onset. At last visit, 48.4% of patients were wheelchair bound at average age of 15.4 years. Twenty percent of the patients had respiratory involvement, with most of them requiring non-invasive ventilation. Cardiomyopathy was present in 14% of patients. Approximately 60% of SGCA patients carried one of the following mutations, either as homozygous or heterozygous: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in SGCG patients were c.521delT or c.848G>A. This study reports clinical and molecular data in sarcoglycanopathies European patients. Sarcoglycanopathies are rare diseases and our European network emphasizes the importance of international efforts to collect detailed clinical data on large cohort of patients. Our study provides data that could be important in the design of natural history studies in view of the development of new potential therapeutic approaches for sarcoglycanopathies.