Survival and severity in dominant cerebellar ataxias.
Inherited spinocerebellar ataxias (SCAs) are known to be genetically and clinically heterogeneous. Whether severity and survival are variable, however, is not known. We, therefore, studied survival and severity in 446 cases and 509 relatives with known mutations. Survival was 68 years [95% CI: 65-70] in 223 patients with polyglutamine expansions versus 80 years [73-84] in 23 with other mutations (P < 0.0001). Disability was also more severe in the former: at age 60, 30% were wheelchair users versus 3% with other SCAs (P < 0.001). This has implications for genetic counseling and the design of therapeutic trials.
AP-HP, Genetic Department, Pitié-Salpêtrière University Hospital F-75013, Paris, France ; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06 UMR S 1127, INSERM U 1127, CNRS UMR 7225, ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital F-75013, Paris, France.
Marie-Lorraine
ML
Monin
Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, UMR S 1136, INSERM U 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique F-75013, Paris, France ; AP-HP, Biostatistics Unit, Groupe Hospitalier Pitié-Salpêtrière F-75013, Paris, France.
Sophie
S
Tezenas du Montcel
Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06 UMR S 1127, INSERM U 1127, CNRS UMR 7225, ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital F-75013, Paris, France ; Department of Neurology, CHRU Guy de Chauliac Montpellier, France.
Cecilia
C
Marelli
AP-HP, Genetic Department, Pitié-Salpêtrière University Hospital F-75013, Paris, France.
Cecile
C
Cazeneuve
AP-HP, Genetic Department, Pitié-Salpêtrière University Hospital F-75013, Paris, France.
Perrine
P
Charles
Department of Neurology, Oslo University Oslo, Norway ; Faculty of Medicine, Oslo University Oslo, Norway.
Chantal
C
Tallaksen
Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06 UMR S 1127, INSERM U 1127, CNRS UMR 7225, ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital F-75013, Paris, France.
Sylvie
S
Forlani
Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06 UMR S 1127, INSERM U 1127, CNRS UMR 7225, ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital F-75013, Paris, France ; Neurogenetics Team, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle épinière F-75013, Paris, France.
Giovanni
G
Stevanin
AP-HP, Genetic Department, Pitié-Salpêtrière University Hospital F-75013, Paris, France ; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06 UMR S 1127, INSERM U 1127, CNRS UMR 7225, ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital F-75013, Paris, France.
Alexis
A
Brice
AP-HP, Genetic Department, Pitié-Salpêtrière University Hospital F-75013, Paris, France ; Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06 UMR S 1127, INSERM U 1127, CNRS UMR 7225, ICM (Brain and Spine Institute) Pitié-Salpêtrière Hospital F-75013, Paris, France.
Alexandra
A
Durr