Distal myopathy secondary to a mutation in myotilin

Abstract

Distal myopathies are inherited primary muscle and may be caused by defects in structural components of the sarcomere. We present a family with a distal myopathy secondary to a mutation in myotilin. A 70-year-old male reported progressive difficulty walking from his early 50s when he developed a tendency for his feet to flap followed by increasing problems rising from a chair. A younger sister had identical symptoms and their father had an abnormal gait from his fifth decade. On examination, he had a lordotic gait and a distal pattern of weakness in his lower limbs. Creatine kinase was marginally raised and an MRI of his legs showed a distinctive pattern of fatty replacement of muscle. Muscle biopsy revealed non-selective fibre atrophy and numerous eosinophilic inclusions surrounded by asophilic granules. Molecular genetic analysis of titan was normal but a myotilin S60C missense mutation was found in both siblings. Myotilin is a 57 kDa Z-disc component that interacts with alpha-actinin, filamin-C, calsarcin and actin which controls sarcomere assembly. Seven mutations have been reported which give rise to two phenotypes—either LGMD1A or a distal myofibrillar myopathy. This family is only the second to be reported with this particular mutation