Myopathies associated with β-tropomyosin mutations

Abstract

Mutations in TPM2, encoding β-tropomyosin, have recently been found to cause a range of muscle disorders. We review the clinical and morphological expression of the previously reported mutations illustrating the heterogeneity of β-tropomyosin-associated diseases and describe an additional case with a novel mutation. The manifestations of mutations in TPM2 include non-specific congenital myopathy with type 1 fibre predominance, nemaline myopathy, cap disease and distal arthrogryposis. In addition, Escobar syndrome with nemaline myopathy is a manifestation of homozygous truncating β-tropomyosin mutation. Cap disease appears to be the most common morphological manifestation. A coarse intermyofibrillar network and jagged Z lines are additional frequent changes. The dominant β-tropomyosin mutations manifest either as congenital myopathy or distal arthrogryposis. The various congenital myopathies are usually associated with moderate muscle weakness and no congenital joint contractures. The distal arthrogryposis syndromes associated with TPM2 mutations include the less severe forms, with congenital contractures mainly of the hands and feet and mild or no muscle weakness. The dominant TPM2 mutations include amino acid deletions/insertions and missense mutations. There is no clear relation between the type of mutations or the localisation of the mutated residue in the β-tropomyosin molecule and the clinical and morphological phenotype.