Background: Sex is a significant risk factor in many neurodegenerative disorders. A better understanding of the molecular mechanisms behind sex differences could help develop more targeted therapies that would lead to better outcomes. Untreated spinal muscular atrophy (SMA) is the leading genetic motor disorder causing infant mortality. SMA has a broad spectrum of severity ranging from prenatal death to infant mortality to normal lifespan with some disability. Scattered evidence points to a sex-specific vulnerability in SMA. However, the role of sex as a risk factor in SMA pathology and treatment has received limited attention.
Objective: Systematically investigate sex differences in the incidence, symptom severity, motor function of patients with different types of SMA, and in the development of SMA1 patients.
Methods: Aggregated data of SMA patients were obtained from the TREAT-NMD Global SMA Registry and the Cure SMA membership database by data enquiries. Data were analyzed and compared with publicly available standard data and data from published literature.
Results: The analysis of the aggregated results from the TREAT-NMD dataset revealed that the male/female ratio was correlated to the incidence and prevalence of SMA from different countries; and for SMA patients, more of their male family members were affected by SMA. However, there was no significant difference of sex ratio in the Cure SMA membership dataset. As quantified by the clinician severity scores, symptoms were more severe in males than females in SMA types 2 and 3b. Motor function scores measured higher in females than males in SMA types 1, 3a and 3b. The head circumference was more strongly affected in male SMA type 1 patients.
Conclusions: The data in certain registry datasets suggest that males may be more vulnerable to SMA than females. The variability observed indicates that more investigation is necessary to fully understand the role of sex differences in SMA epidemiology, and to guide development of more targeted treatments.
Keywords: Spinal muscular atrophy; development; male/female ratio; motor function; severity; sex difference.