NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.
Clinical characteristics: Nemaline myopathy (referred to in this entry as NM) is characterized by weakness, hypotonia, and depressed or absent deep tendon reflexes. Muscle weakness is usually most severe in the face, the neck flexors, and the proximal limb muscles. The clinical classification defines six forms of NM, which are classified by onset and severity of motor and respiratory involvement: Considerable overlap occurs among the forms. There are significant differences in survival between individuals classified as having severe, intermediate, and typical congenital NM. Severe neonatal respiratory disease and the presence of arthrogryposis multiplex congenita are associated with death in the first year of life. Independent ambulation before age 18 months is predictive of survival. Most children with typical congenital NM are eventually able to walk.
Diagnosis/testing: Diagnosis is based on clinical findings and the observation of characteristic rod-shaped structures (nemaline bodies) on muscle biopsy stained with Gomori trichrome. Pathogenic variants have been identified in ten different genes, six of which encode protein components of the muscle thin filament, while three appear to be involved in the protein turnover in the muscle sarcomere via the ubiquitin proteosome pathway.
Management: Treatment of manifestations: Aggressive treatment of lower respiratory tract infections, ventilator use for nocturnal hypoxia, preoperative assessment of pulmonary function to ensure optimal timing of surgical procedures and to minimize anesthetic risk, monitoring of nutritional status, special feeding techniques, standard care for gastroesophageal reflux, mobility and physical therapy to help prevent joint contractures, speech therapy, and assessment of cardiac status. Surveillance: Routine assessment for respiratory function, scoliosis, joint contractures, and the need for assistive devices. Agents/circumstances to avoid: Neuromuscular blocking agents, because of possible association with malignant hyperthermia susceptibility.
Genetic counseling: NM is inherited in an autosomal dominant or autosomal recessive manner. In one series, approximately 20% of cases were autosomal recessive, approximately 30% autosomal dominant, and approximately 50% simplex (i.e., single occurrences in a family) representing heterozygosity for a de novo dominant pathogenic variant or biallelic autosomal recessive pathogenic variant. Accurate recurrence risk information requires determination of the mode of inheritance, if possible, through pedigree analysis and a combination of clinical evaluation, molecular genetic testing, and muscle biopsy of the parents. Carrier testing for at-risk relatives in families with autosomal recessive NM is possible if the pathogenic variants in the family are known. Prenatal molecular genetic testing is possible for pregnancies at increased risk for autosomal dominant and autosomal recessive NM if the pathogenic variant(s) in the family are known.
Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.