Valuable resource for much-needed research
Canada can well be proud of a collaborative national initiative resulting in the establishment of a large database of HSP information, providing invaluable information that will help researchers everywhere finding effective treatments in the future.
.
526 HSPers are in the Canadian database that will provide critical information for the development of a ‘natural history of HSP’ that is so important as a benchmark in evaluating potential treatments.
OBJECTIVE:
To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP.
METHODS:
We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65).
RESULTS:
A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset (p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04-548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes (p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI (p = 0.014).
CONCLUSIONS:
The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.
SOURCE: Neurol Genet. 2016 Dec 5;3(1):e122. eCollection 2017. PMID: 27957547 PMCID: PMC5141523 DOI: 10.1212/NXG.0000000000000122 [PubMed – in process]
Clinical and genetic study of hereditary spastic paraplegia in Canada.
Chrestian N1, Dupré N1, Gan-Or Z1, Szuto A1, Chen S1, Venkitachalam A1, Brisson JD1, Warman-Chardon J1, Ahmed S1, Ashtiani S1, MacDonald H1, Mohsin N1, Mourabit-Amari K1, Provencher P1, Boycott KM1, Stavropoulos DJ1, Dion PA1, Ray PN1, Suchowersky O1, Rouleau GA1, Yoon G1.
1 Division of Neurology (N.C., G.Y.), Division of Clinical and Metabolic Genetics (S. Ahmed, H.M., G.Y.), Department of Paediatrics, University of Toronto, The Hospital for Sick Children; Faculty of Medicine (N.C., N.D., J.-D.B., K.M.-A.), Laval University, Quebec City; Department of Neurological Sciences (N.D., P.P.), CHU de Québec; Department of Neurology and Neurosurgery (Z.G.-O., N.M., P.A.D., G.A.R.), McGill University, Montreal Neurological Institute, Quebec; Department of Medical Genetics (A.S.), University of Montreal, CHUM, Quebec; The Hospital for Sick Children Research Institute (S.C.), Child Health Evaluative Sciences/Biostatistics Design & Analysis Unit, Toronto, Ontario; Department of Medicine (A.V., O.S.), Division of Neurology, Department of Medical Genetics (S. Ashtiani, O.S.), University of Alberta, Edmonton; Department of Genetics (J.W.-C., K.M.B.), Children’s Hospital of Eastern Ontario, Ottawa; CHU de Québec (K.M.-A.), Hôpital Enfant-Jésus, Quebec City; Department of Paediatric Laboratory Medicine (D.J.S., P.N.R.), The Hospital for Sick Children, Toronto, Ontario; and Department of Molecular Genetics (P.N.R.), The University of Toronto, Canada.