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Adult Onset Spinocerebellar Ataxia in a Canadian Movement Disorders Clinic

Published online by Cambridge University Press:  02 December 2014

Scott Kraft ,
Sarah Furtado ,
Ranjit Ranawaya ,
Jillian Parboosingh ,
Stacey Bleoo ,
Karen McElligott ,
Peter Bridge ,
Sian Spacey ,
Shyamal Das  and
Oksana Suchowersky
Scott Kraft*
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
Sarah Furtado
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
Ranjit Ranawaya
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
Jillian Parboosingh
Affiliation:
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
Stacey Bleoo
Affiliation:
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
Karen McElligott
Affiliation:
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
Peter Bridge
Affiliation:
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
Sian Spacey
Affiliation:
Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Shyamal Das
Affiliation:
Bangur Neurological Institute, Kolkata, India
Oksana Suchowersky
Affiliation:
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
*
The Movement Disorders Program, Dept. of Clinical Neurosciences, University of Calgary, 3350 Hospital Dr. NW, Calgary, Alberta, Canada T2N 4N1.
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Abstract:

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Background:

The spinocerebellar ataxias (SCAs) are a genetically and clinically heterogeneous group of neurodegenerative disorders. Relative frequencies vary within different ethnic groups and geographical locations.

Objectives:

1) To determine the frequencies of hereditary and sporadic adult onset SCAs in the Movement Disorders population; 2) to assess if the fragile X mental retardation gene 1 (FMR1) premutation is found in this population.

Methods:

A retrospective chart review of individuals with a diagnosis of adult onset SCA was carried out. Testing for SCA types 1, 2, 3, 6, 7, and 8, Dentatorubral-pallidoluysian atrophy (DRPLA), Friedreich ataxia and the FMR1 expansion was performed.

Results:

A total of 69 patients in 60 families were identified. Twenty-one (35%) of the families displayed autosomal dominant and two (3.3%) showed autosomal recessive (AR) pattern of inheritance. A positive but undefined family history was noted in nine (15%). The disorder appeared sporadic in 26 patients (43.3%). In the AD families, the most common mutation was SCA3 (23.8%) followed by SCA2 (14.3%) and SCA6 (14.3%). The SCA1 and SCA8 were each identified in 4.8%. FA was found in a pseudodominant pedigree, and one autosomal recessive pedigree. One sporadic patient had a positive test (SCA3).Dentatorubral-pallidoluysian atrophy and FMR1 testing was negative.

Conclusion:

A positive family history was present in 53.3% of our adult onset SCA patients. A specific genetic diagnosis could be given in 61.9% of dominant pedigrees with SCA3 being the most common mutation, followed by SCA2 and SCA6. The yield in sporadic cases was low. The fragile X premutation was not found to be responsible for SCA.

Résumé:

RÉSUMÉ: Contexte:

Les ataxies spinocérébelleuses (ASCs) constituent un groupe hétérogène de maladies neurodégénératives tant au point de vue génétique qu’au point de vue clinique. Leur fréquence relative est très variable selon le groupe ethnique et le lieu géographique.

Objectifs:

1) déterminer la fréquence d’ASCs héréditaires et sporadiques débutant chez l’adulte chez des patients fréquentant une clinique de désordres du mouvement ; 2) évaluer si on retrouve chez ces patients des prémutations du gène FMR1 causant le syndrome de retard mental du X fragile.

Méthodes:

Nous avons procédé à une revue rétrospective de dossiers de patients chez qui un diagnostic d’ASC de l’adulte a été posé. Des tests de biologie moléculaire ont été faits pour détecter des anomalies des gènes responsables de l’ASC de type 1, 2, 3, 6, 7 et 8, de l’atrophie dentato-rubro-pallido-luysienne (ADRPL), de l’ataxie de Friedrich (AF) ainsi que l’expansion de FMR1.

Résultats:

69 patients appartenant à 60 familles différentes ont été identifiés. Chez 21 familles (35%), l’hérédité était autosomique dominante (AD) et chez 2 (3,3%) l’hérédité était autosomique récessive (AR). Une histoire familiale positive mal définie était présente chez 9 familles (15%). La maladie semblait sporadique chez 26 patients (43,3%). Chez les familles où l’hérédité était AD, la mutation la plus fréquents était une mutation du gène ASC3 (23,8%) suivie d’ASC2 (14,3%) et d’ASC6 (14,3%). Une mutation du gène ASC1 et ASC8 a été identifiée chez 4,8% des patients. Une mutation du gène de l’AF a été identifiée dans un pedigree où la maladie était pseudo dominante et dans un où la maladie était AR. Chez un cas sporadique on a trouvé une mutation du gène ASC3. Les tests pour l’ADRPL et le FMR1 étaient négatif.

Conclusion:

Une histoire familiale positive était présente chez 53,3% des patients atteints d’ASC adulte. Un diagnostic génétique spécifique a pu être établi chez 61,9% des pedigrees où l’hérédité était dominante et une mutation du gène ASC3 était l’anomalie la plus fréquente, suivie d’ASC2 et d’ASC6. Le rendement était faible chez les cas sporadiques. La prémutation du gène responsable du syndrome du X fragile n’était pas responsable de l’ASC chez nos cas.

Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 32 , Issue 4 , November 2005 , pp. 450 - 458
Copyright
Copyright © The Canadian Journal of Neurological 2005

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