Spinal muscular atrophy with respiratory distress type 1: A multicenter retrospective study

Neuromuscul Disord. 2019 Feb;29(2):114-126. doi: 10.1016/j.nmd.2018.10.002. Epub 2018 Oct 31.

Abstract

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disorder characterized by progressive motor and respiratory decline during the first year of life. Early and late-onset cases have recently been reported, although not meeting the established diagnostic criteria, these cases have been genotyped. We thus conducted a national multicenter observational retrospective study to determine the prognosis of children with SMARD1 according to their phenotype. We recorded all known French pediatric cases with mutations identified on the immunoglobulin μ-binding protein 2 gene and the presence of respiratory symptoms. Thirty centers provided 22 observations. A diaphragmatic palsy was diagnosed 1.5 months (p = 0.02) after first respiratory symptoms, and hypotonia preceded areflexia by 4 months (p = 0.02). Early onset of symptoms leading to specialist consultation before the age of 3 months was associated with a significantly worse prognosis (p < 0.01). Among the 6 patients who were still alive, all were tracheostomized. Only one case survived beyond 2 years without artificial ventilation. The remaining patients died at a median age of 7 months. Our results may help pediatricians to provide medical information to parents and improve the decision-making process of setting up life support.

Keywords: DSMA1; Heterogeneity; IGHMBP2; Multicenter; Prognosis; SMARD1.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Female
  • France
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Muscular Atrophy, Spinal / diagnosis*
  • Muscular Atrophy, Spinal / genetics
  • Mutation
  • Phenotype
  • Prognosis
  • Respiration, Artificial
  • Respiratory Distress Syndrome, Newborn / diagnosis*
  • Respiratory Distress Syndrome, Newborn / genetics
  • Retrospective Studies
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • IGHMBP2 protein, human
  • Transcription Factors

Supplementary concepts

  • Spinal muscular atrophy with respiratory distress 1