Congenital Fiber-Type Disproportion Type 1

Abstract

Congenital myopathy with fiber-type disproportion (selective hypotrophy of type 1 fibers) is a genetically heterogeneous condition characterized by hypotonia and generalized muscle weakness, which is usually present at birth or within the first year of life. Weakness affects not only the proximal limb-girdle muscles but also the facial muscles, resulting in a long face, high-arched palate and prominent upper lip, and ophthalmoplegia. Approximately 30% of patients have respiratory involvement and feeding difficulties. Joint contractures in ankles, fingers, hips, elbows, and knees, spinal deformities, kyphoscoliosis, lordosis, hip dislocation, and talipes equinovarus may also be present. Cardiac involvement, cognitive impairment, and cryptorchidism are rare. Muscle biopsy shows a characteristic but not specific selective hypotrophy of type 1 fibers, which are also prevalent as compared to type 2 fibers, which are either normal or hypertrophied. Causative mutations have been identified in several genes, including ACTA1, which encodes the sarcomeric protein alpha-actin (Tables 43.1 and 43.2).