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 ...view middle of the document...
Although the clinical symptoms closely mimic each other, the genetic basis differs from disease to disease. This review will focus on nemaline myopathy, as it is the most common of the congenital myopathies. INCIDENCE
Shy et al1 and Conen et al2 first described the disease in 1963. Because of the presence of thread or rod structures (Greek nema =thread) in muscle fibers, the term nemaline myopathy was coined by Shy et al1 and this is now widely accepted. The disease has been classified into 3 major forms including the severe infantile (congenital), benign congenital (mild, nonprogressive or slowly progressive) and adult onset forms. A recent classification proposed by European Neuromuscular Center Workshop further subdivided the benign congenital form into 3 additional subtypes of intermediate congenital, typical congenital and childhood-onset forms.3 However, this classification is not so clear-cut and is not of practical value in followup of these patients.3 1) Genetic aspects4
The actual incidence of congenital myopathy is unknown. In my laboratory at the National Center of Neurology and Psychiatry, from 1979 to 2000, we have examined muscle biopsies from 449 patients with congenital myopathy (Table 1). During the same period, we had 511 cases of Duchenne muscular dystrophy, therefore congenital myopathy does not appear to be a rare disease, but is relatively common among the childhood myopathies.
The disease is inherited through an autosomal dominant or recessive trait. In an Australian family with an autosomal dominant inheritance, a gene mutation was first found in slow alphatropomyosin (TPM3).5 Subsequently mutations were found in the Nebulin gene (NEB) in patients with an autosomal recessive trait6, and alphaactin gene (ACTA1) mostly in patients with the
Address for correspondence: Dr I. Nonaka, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan. Fax: (81)-42-346-1774; e-mail: firstname.lastname@example.org
Neurol J Southeast Asia
Table 1: Incidence of congenital myopathy (1979-2000: National Center of Neurology and Psychiatry)
Types of congenital myopathy Nemaline myopathy Severe infantile form Benign congenital form Adult onset form Central core disease Myotubular (centronuclear) myopathy Severe infantile myotubular myopathy Congenital fiber type disproportion Congenital myopathy without specific features (Minimal change myopathy) Miscellaneous Number of patients (%) 121 (27%) 43 53 25 27 (6%) 42 (9%) 30 (7%) 89 (20%) 31 (7%) 109 (24%)
Total number of patients Duchenne muscular dystrophy diagnosed during the same period
severe infantile form and actinopathy.7 Recently, a mutation in troponin T1 (TNNT1) was found in an autosomal dominant Amish family.8 Since all mutations were found in genes encoding actin filament components, nemaline myopathy is a disorder of sarcomeric thin filaments or Z disc. 2) Clinical findings
Severe infantile (congenital) form