Patients meeting the clinical criteria for HSP in Alberta were recruited through Neurogenetics clinics in Edmonton and Calgary between 2012 and 2019, and enrolled in an observational study. Clinical features were collected via a standardized inventory. Research whole exome sequencing was performed, and results confirmed in an accredited lab. For some patients, additional testing with commercial multi-gene panels was conducted. Disability was assessed using Spastic Paraplegia Rating Scale (SPRS).

A total of 105 HSP patients were enrolled and five patients were lost to follow up. Sixty-seven patients (67%) were found to have mutations in 21 genes. The majority of cases had complicated HSP (56%). Inheritance patterns were 32% autosomal dominant, 21% autosomal recessive, 4% X-linked, and 43% sporadic. Mutations were most frequent in SPAST (27%), SPG7 (22%), SACS (7%), SPG11 (6%), CAPN1 (4%), and SYNE1 (4%). Patients with SPG4 (SPAST) had an age of onset ranging from 1 to 38 years while SPG7 ranged from 13 to 55 years. Compared to SPG4, patients with SPG7 had a lower mean SPRS score (26.00 ± 12.2 vs.14.8 ± 5.9). Abnormalities of brain MRI were more frequently observed in patients SACS (80%, progressive cerebellar atrophy) and SPG11 (50%, thin corpus callosum). SPG7 was more associated with polyneuropathy.