Chapter 95 - Hereditary Inclusion-Body Myopathies

Abstract

The hereditary inclusion-body myopathies (HIBM) include muscle disorders with autosomal recessive or dominant inheritance and muscle pathology characterized by the presence of muscle fibers with rimmed vacuoles and the collection of cytoplasmic or nuclear 15–21-nm diameter tubulofilaments. The most common form of HIBM is due to mutations of the GNE gene that possibly generate an imbalance of sialic acid metabolism leading to muscle fiber degeneration. Mutations of the valosin-containing protein are instead responsible for hereditary inclusion-body myopathy with Paget disease of the bone and frontotemporal dementia (IBMPFD), with the three phenotypic features having a variable penetrance. IBMPFD represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the myosin heavy chain IIa gene that exerts a pathogenic effect through interference with filaments assembly or functional defects in ATPase activity.