The clinical course and genotype-phenotype correlations in 41 patients aged 1-60 years with selenoprotein-related myopathy (SEPNRM) due to SEPN1 gene mutations were evaluated retrospectively in a study at The Dubowitz Neuromuscular Center, London, and other centers in the UK. Mean age at onset was 2.7 years, ranging from birth to second decade. One third were congenital in onset with hypotonia. In 46%, onset was at 6 months to 5 years of age with delayed motor milestones. Creatine kinase was minimally elevated in 16% and markedly elevated only in 1. All but 2 patients remained independently ambulant. Respiratory insufficiency generally developed and nocturnal noninvasive ventilation was started at a mean age of 13.9 years. Scoliosis preceded by rigid spine developed at a mean age of 10 years and was treated surgically at 13.9 years. Joint contractures were present in 26 (63%) at a mean age of 10.4 years; 2 patients had finger contractures at birth. Motor abilities remained static over time. Twenty of 35 (57%) were underweight. Two patients died from respiratory failure at age 10 and 22 years. Muscle biopsy performed in 34 patients showed multiminicores and nonspecific myopathic changes. Genetic sequencing showed 14 new SEPN1 mutations, 48% missense. [1]

COMMENT. This study expands the spectrum of myopathy with SEPN1 mutations, with respect to severity of the disease, age at onset, and long-term outcome.