Clinical and genetic characteristics, prognostic risk factors, and classification of nemaline myopathy (NM) are examined in a study of 143 cases identified at two centers in Australia and North America and reported from the Neurogenetics Research Unit, University of Sydney, Australia; Children’s Hospital, Boston; and other centers. Of the 143 cases, 23(16%) were typed as severe congenital NM, 29(20%) were intermediate congenital, 66(46%) typical congenital, 19(13%) of childhood onset, and 6(4%) of adult onset. Severe congenital cases had absence of spontaneous movements and respiration, and contractures (arthrogryposis multiplex congenita (AMC) in 8 cases) and fractures at birth, and 74% died of respiratory insufficiency (ld-1.3y). Intermediate congenital cases presented neonatally (<28 days) with hypotonia, their motor milestones were delayed, they developed contractures (only 1 AMC) in early childhood, they had respiratory symptoms, and were confined to a wheelchair by 11 years, and 28% died (2w-2.9y). Typical congenital cases presented in infancy (usually after 28 days) or early childhood, 1/3 had neonatal hypotonia, weakness was initially proximal and later distal, most were ambulant before 18 months of age, the course was slowly progressive in 23%, and 6% died (6-19y). Childhood onset cases presented with delayed motor milestones and facial diplegia, but diagnosis was delayed for years after onset, and only 5% died (46y). Adult onset cases presented at 41 to 59 years of age, 4(66%) were symptomatic for up to 20 years before diagnosis, all had mild facial and proximal weakness, 4 had myalgia, and none died. Additional symptoms in some congenital cases included food intolerance with gavage feeding and gastrostomy, bulbar dysfunction with dysarthria, drooling and aspiration, cardiac dysfunction, and seizures. Electromyography was abnormal in 42 of 64 patients tested. Inheritance was autosomal recessive in 29 cases (20%), autosomal dominant in 41(29%), and sporadic in 72(50%). Risk factors for early mortality, mainly in severe congenital cases, were arthrogryposis, neonatal respiratory failure, and delayed motor milestones. Motor outcome was correlated with respiratory involvement; patients requiring ventilatory support in the first year never walked, In children surviving the neonatal period, muscle weakness and respiratory function improved with increasing age. [1]

COMMENT. Nemaline myopathy, first described by Shy and coworkers in 1963, is characterized by a slowly progressive, or static weakness and hypotonia of pelvic and other muscles, and threadlike, intracellular rods, staining red with modified trichrome stain, in muscle fibers. The term nemaline is derived from the Greek word nema or thread. Inheritance is autosomal dominant, recessive, or sporadic. Clinical classification of nemaline myopathy (NM) is determined by three factors: 1) respiratory function, 2) severity and distribution of weakness, and 3) motor milestones. Severe congenital subtype has clearly defined symptoms with a poor outcome. Intermediate and typical congenital subtypes are difficult to distinguish in infancy but can be separated in later childhood; patients with typical congenital NM crawl before 12 months and walk before 18 months, whereas intermediate cases are more delayed, the course is more progressive, and mortality is significantly higher. Childhood- and adult-onset cases have overlapping characteristics and a good prognosis. Prenatal expression of NM has been associated with fetal akinesia sequence (Lammens et al, 1997, cited by above authors), and frequent obstetric complications. Mortality, especially in severe and intermediate congenital subtypes, is almost invariably caused by respiratory insufficiency, and motor outcome is correlated with respiratory involvement. After the neonatal period, treatment of pulmonary infection and feeding problems can lower mortality. For earlier references to congenital nemaline myopathy, see Progress in Pediatric Neurology III, PNB Publ, 1997;pp349-351).