Adults with spinal muscular atrophy: a large-scale natural history study shows gender effect on disease

J Neurol Neurosurg Psychiatry. 2022 Dec;93(12):1253-1261. doi: 10.1136/jnnp-2022-329320. Epub 2022 Oct 11.

Abstract

Background: Natural history of spinal muscular atrophy (SMA) in adult age has not been fully elucidated yet, including factors predicting disease progression and response to treatments. Aim of this retrospective, cross-sectional study, is to investigate motor function across different ages, disease patterns and gender in adult SMA untreated patients.

Methods: Inclusion criteria were as follows: (1) clinical and molecular diagnosis of SMA2, SMA3 or SMA4 and (2) clinical assessments performed in adult age (>18 years).

Results: We included 64 (38.8%) females and 101 (61.2%) males (p=0.0025), among which 21 (12.7%) SMA2, 141 (85.5%) SMA3 and 3 (1.8%) SMA4. Ratio of sitters/walkers within the SMA3 subgroup was significantly (p=0.016) higher in males (46/38) than in females (19/38). Median age at onset was significantly (p=0.0071) earlier in females (3 years; range 0-16) than in males (4 years; range 0.3-28), especially in patients carrying 4 SMN2 copies. Median Hammersmith Functional Rating Scale Expanded scores were significantly (p=0.0040) lower in males (16, range 0-64) than in females (40, range 0-62); median revised upper limb module scores were not significantly (p=0.059) different between males (24, 0-38) and females (33, range 0-38), although a trend towards worse performance in males was observed. In SMA3 patients carrying three or four SMN2 copies, an effect of female sex in prolonging ambulation was statistically significant (p=0.034).

Conclusions: Our data showed a relevant gender effect on SMA motor function with higher disease severity in males especially in the young adult age and in SMA3 patients.

Keywords: MOTOR NEURON DISEASE; NEUROMUSCULAR; SPINAL MUSCULAR ATRO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child, Preschool
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Humans
  • Male
  • Muscular Atrophy, Spinal* / epidemiology
  • Muscular Atrophy, Spinal* / genetics
  • Retrospective Studies
  • Spinal Muscular Atrophies of Childhood* / drug therapy
  • Spinal Muscular Atrophies of Childhood* / epidemiology
  • Spinal Muscular Atrophies of Childhood* / genetics
  • Young Adult