Congenital myopathies: Natural history of a large pediatric cohort

Neurology. 2015 Jan 6;84(1):28-35. doi: 10.1212/WNL.0000000000001110. Epub 2014 Nov 26.


Objective: To assess the natural history of congenital myopathies (CMs) due to different genotypes.

Methods: Retrospective cross-sectional study based on case-note review of 125 patients affected by CM, followed at a single pediatric neuromuscular center, between 1984 and 2012.

Results: Genetic characterization was achieved in 99 of 125 cases (79.2%), with RYR1 most frequently implicated (44/125). Neonatal/infantile onset was observed in 76%. At birth, 30.4% required respiratory support, and 25.2% nasogastric feeding. Twelve percent died, mainly within the first year, associated with mutations in ACTA1, MTM1, or KLHL40. All RYR1-mutated cases survived and did not require long-term ventilator support including those with severe neonatal onset; however, recessive cases were more likely to require gastrostomy insertion (p = 0.0028) compared with dominant cases. Independent ambulation was achieved in 74.1% of all patients; 62.9% were late walkers. Among ambulant patients, 9% eventually became wheelchair-dependent. Scoliosis of variable severity was reported in 40%, with 1/3 of (both ambulant and nonambulant) patients requiring surgery. Bulbar involvement was present in 46.4% and required gastrostomy placement in 28.8% (at a mean age of 2.7 years). Respiratory impairment of variable severity was a feature in 64.1%; approximately half of these patients required nocturnal noninvasive ventilation due to respiratory failure (at a mean age of 8.5 years).

Conclusions: We describe the long-term outcome of a large cohort of patients with CMs. While overall course is stable, we demonstrate a wide clinical spectrum with motor deterioration in a subset of cases. Severity in the neonatal/infantile period is critical for survival, with clear genotype-phenotype correlations that may inform future counseling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Consanguinity
  • Cross-Sectional Studies
  • Deglutition Disorders / etiology
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mobility Limitation
  • Muscle Proteins / genetics*
  • Muscle, Skeletal* / pathology
  • Myopathies, Nemaline / complications
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / pathology
  • Myopathies, Structural, Congenital / complications
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / pathology
  • Myopathy, Central Core / complications
  • Myopathy, Central Core / genetics*
  • Myopathy, Central Core / pathology
  • Respiratory Insufficiency / etiology
  • Retrospective Studies
  • Scoliosis / etiology
  • Young Adult


  • Muscle Proteins