Hereditary Spastic Paraplegia in Alberta: Lessons from a Well-Defined Cohort Including the Indigenous Population

Area of Science:

• Neurology
• Genetics
• Epidemiology

Background:

• Hereditary spastic paraplegias (HSP) are rare neurological disorders characterized by leg spasticity and gait impairment.
• Over 50% of HSP cases remain genetically unsolved, with limited understanding of HSP genetics in Indigenous populations.

Purpose of the Study:

• To characterize the clinical, radiological, and genetic features of HSP in Alberta, Canada.
• To evaluate genetic variability of HSP across different ethnic groups within Alberta.

Main Methods:

• An observational study enrolled 100 patients from 86 families with HSP between 2012 and 2021.
• Genetic testing was conducted through research and/or clinical laboratories to identify pathogenic variants.

Main Results:

• The overall prevalence of HSP in Alberta was 2.3 per 100,000, with 2.8 per 100,000 in the Indigenous population.
• Pathogenic variants were identified in 56% of families across 17 genes (SPAST, SPG7, SPG11, CAPN1, SACS most common).
• Genetic diagnoses were confirmed in White (54%), Indigenous (62.5%), Asian (50%), and Middle Eastern (66.7%) families, with unique variants found in Indigenous families.

Conclusions:

• This study provides the first detailed examination of HSP prevalence and genetic causes in Alberta's Indigenous population.
• Findings underscore the importance of considering ethnic diversity when diagnosing and researching HSP phenotypes and genotypes.