Clinical and pathologic aspects of congenital myopathies
Ikuya NONAKA MD
National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan Abstract
The term “congenital myopathy” is applied to muscle disorders presenting in infancy with generalized muscle weakness and hypotonia followed by delayed developmental milestones. The myopathy has been differentiated diagnostically on the basis of their morphologic characteristics and includes nemaline myopathy, central core disease, myotubular (centronuclear) myopathy and congenital fiber type disproportion. In most of these disorders, there are 3 distinct subtypes: severe infantile, benign congenital and adult onset forms. The mode of inheritance and gene loci are variable, although each disorder shares the common clinical features including facial and prominent neck flexor weakness and preferential respiratory muscle involvement. All mutations identified in nemaline myopathy are localized to the actin filament components, suggesting that the disease is related to sarcoplasmic thin filaments or Z-protein abnormalities. On the other hand, X-linked myotubular myopathy has mutations in a family of tyrosine phosphatase (myotubularin gene) and central core disease in ryanodine receptor gene. In all these disorders, the common pathologic features are small muscle fibers with type 1 fiber atrophy and predominance, which account for the small muscle bulk and generalized muscle weakness. INTRODUCTION NEMALINE MYOPATHY

The term congenital myopathy is applied to muscle disorders presenting with generalized muscle weakness and hypotonia from early infancy with delayed developmental milestones. Dysmorphic features such as elongated face, scoliosis and contracture of joints are common. The congenital myopathies have been classified into various diseases based on pathologic characteristics, including nemaline myopathy, central