Spinal Muscular Atrophy (SMA) Subtype Concordance in Siblings: Findings From the Cure SMA Cohort

J Neuromuscul Dis. 2020;7(1):33-40. doi: 10.3233/JND-190399.


Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous survival of motor neuron 1 (SMN1) gene disruption. Despite a genetic etiology, little is known about subtype concordance among siblings.

Objective: To investigate subtype concordance among siblings with SMA.

Methods: Cure SMA maintains a database of newly diagnosed patients with SMA, which was utilized for this research.

Results: Among 303 sibships identified between 1996 and 2016, 84.8% were subtype concordant. Of concordant sibships, subtype distribution was as follows: Type I, 54.5%; Type II, 31.9%; Type III, 13.2%; Type IV, 0.4%. Subtype and concordance/discordance association was significant (Fisher's exact test; p < 0.0001). Among discordant sibships (chi-square test, p < 0.0001), Types II/III (52.2%) and Types I/II (28.3%) were the most common pairs. No association was found between sibling sex and concordance. Our findings show that most siblings with SMA shared the same subtype concordance (most commonly Type I).

Conclusions: These data are valuable for understanding familial occurrence of SMA subtypes, enabling better individual treatment and management planning in view of new treatment options and newborn screening initiatives.

Keywords: Child; epidemiology; genetics; growth & development; infant; mutation; neuromuscular disease.

MeSH terms

  • Databases, Factual
  • Female
  • Humans
  • Infant
  • Male
  • Muscular Atrophy, Spinal* / classification
  • Muscular Atrophy, Spinal* / epidemiology
  • Muscular Atrophy, Spinal* / genetics
  • Muscular Atrophy, Spinal* / physiopathology
  • Phenotype
  • Siblings*