Clinical Presentation and Early Evolution of Spastic Ataxia of Charlevoix-Saguenay Antoine Duquette, MD, MSc, FRCP(C), 1 * Bernard Brais, MD, MPhil, PhD, FRCP(C), 2 Jean-Pierre Bouchard, MD, FRCP(C) 3 and Jean Mathieu, MD, MSc, FRCP(C) 4 1 Unit e des Troubles du Mouvement Andr e-Barbeau, Services de Neurologie et de M edecine G enique, D epartement de M edecine, Facult e de M edecine et Centre Hospitalier de l’Universit e de Mon- tr eal, Montr eal, Quebec, Canada 2 Departments of Neurology and Neurosurgery and Human Genetics, Montreal Neurological Hospital, Faculty of Medicine, McGill University, Montr eal, Quebec, Canada 3 H^ opital Enfant-J esus, CHU de Qu ebec et D epartement des Scien- ces Neurologiques, Facult e de M edecine de l’Universit e Laval, Qu ebec, Quebec, Canada 4 Complexe Hospitalier de la Sagamie et Facult e de M edecine et des Sciences de la Sant e de l’Universit e de Sherbrooke, Jonquie ` re, Quebec, Canada ABSTRACT Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an increasingly rec- ognized form of spastic ataxia worldwide, but early diagnosis remains a challenge. Methods: We reviewed the initial presentation (n 5 40) and early clinical evolution (n 5 50) of a large ARSACS cohort that was followed at the Saguenay Neuromus- cular clinic. Results: The average age at presentation was 3.41 6 1.55 years. Increased deep tendon reflexes were more common than spasticity initially, and the neuropathy only became apparent clinically in the sec- ond decade. Despite a homogeneous genetic back- ground, some patients showed no signs of neuropathy or spasticity by the age of 18 years. Conclusions: At presentation, ARSACS lacks certain features that are considered typical in adults after years of evolution. Considering that ARSACS is prob- ably under-diagnosed, it should be included in the dif- ferential diagnosis of early onset ataxias with or without pyramidal features and is worthwhile to con- sider in older patients, even when some features are absent. V C 2013 Movement Disorder Society Key Words: spinocerebellar ataxia; spasticity; neu- ropathy; French-Canadian; ARSACS Autosomal recessive spastic ataxia of Charlevoix- Saguenay (ARSACS) was described as a French-Canadian founder effect in 1978. 1 After mutations were uncovered in the SACS gene in French-Canadians, 2 cases were rec- ognized in several countries, including Turkey, 3 Tunisia, 4 Japan, 5 Italy, 6,7 Spain, 8 Belgium, 9 the Netherlands, 10 the United Kingdom, 10 France, 11 Hungary, 12 Serbia, 12 Morocco, 12 Germany, 13 and the United States. 14 With a carrier rate of 1 of 22 individuals in the Charlevoix and Saguenay-Lac-Saint-Jean regions, 15 the disease is readily diagnosed on a clinical basis at an early age in Quebec. However, its prevalence may be underestimated in other populations, as suggested by the presence of SACS muta- tions in 37% of patients with early onset Friedreich- negative ataxia in a Dutch cohort. 10 Although more than 100 SACS mutations have been characterized worldwide, including 12 in the Quebec population, 16 the adult ARSACS clinical picture of progressive ataxia, pyramidal involvement, and axonal neuropathy, with both demyeli- nating and dying-back distal features, remains surpris- ingly uniform. 17 Early ARSACS diagnosis is a challenge outside of Quebec, because awareness of the condition is still relatively low, and a detailed description of the clini- cal characteristics upon initial presentation has yet to be published. Here, we analyze the presentation and early clinical evolution of 71 French-Canadian ARSACS cases from the Saguenay region. Patients and Methods Patients We reviewed all visits of the 71 patients with ARSACS who were seen before the age of 18 years at ------------------------------------------------------------ Additional Supporting Information may be found in the online version of this article. *Correspondence to: Dr. Antoine Duquette, Unit e des troubles du mouvement Andr e-Barbeau, Service de Neurologie, D epartement de M edecine, Centre Hospitalier de l’Universit e de Montr eal, 1560 rue Sher- brooke Est GR-1185, Montr eal, QC, Canada, H2L 4M1; antoine.duquette@umontreal.ca Funding agencies: A.D. was supported by a Fonds de Recherche du Qu ebec-Sant e fellowship, a Bourse de prestige du R eseau Qu eb ecois de Recherche sur le Vieillissement, a Canadian Institute for Health Research (CIHR) clinician-scientist (phase 1) training grant, and a Parkin- son Society Canada fellowship. J.-P.B., B.B., and J.M. were supported by a CIHR and Ataxia of Charlevoix-Saguenay Foundation Team Grant. Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 24 October 2012; Revised: 25 April 2013; Accepted: 29 May 2013 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25604 BRIEF REPORT Movement Disorders, Vol. 00, No. 00, 2013 1