Congenital myopathies: Natural history of a large pediatric cohort.

Abstract

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.

• Authors: Irene Colombo, Mariacristina Scoto, Adnan Y Manzur, Stephanie A Robb, Lorenzo Maggi, Vasantha Gowda, Thomas Cullup, Michael Yau, Rahul Phadke, Caroline Sewry, Heinz Jungbluth, Francesco Muntoni
• Journal: Neurology (Neurology) Vol. 84 Issue 1 Pg. 28-35 (Jan 06 2015) ISSN: 1526-632X [Electronic] United States
• PMID: 25428687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Academy of Neurology.

Chemical References

• Muscle Proteins

Topics

• 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, genetics, pathology)
• Myopathies, Structural, Congenital (complications, genetics, pathology)
• Myopathy, Central Core (complications, genetics, pathology)
• Respiratory Insufficiency (etiology)
• Retrospective Studies
• Scoliosis (etiology)
• Young Adult