Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies

Détails

Ressource 1Télécharger: REF.pdf (329.60 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
ID Serval
serval:BIB_C80784A4BD27
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies
Périodique
Brain
Auteur⸱e⸱s
Le Ber  I., Moreira  M. C., Rivaud-Pechoux  S., Chamayou  C., Ochsner  F., Kuntzer  T., Tardieu  M., Said  G., Habert  M. O., Demarquay  G., Tannier  C., Beis  J. M., Brice  A., Koenig  M., Durr  A.
ISSN
0006-8950 (Print)
Statut éditorial
Publié
Date de publication
12/2003
Peer-reviewed
Oui
Volume
126
Numéro
Pt 12
Pages
2761-72
Notes
Case Reports Journal Article Research Support, Non-U.S. Gov't --- Old month value: Dec
Résumé
Ataxia with ocular motor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia (ARCA) associated with oculomotor apraxia, hypoalbuminaemia and hypercholesterolaemia. The gene APTX, which encodes aprataxin, has been identified recently. We studied a large series of 158 families with non-Friedreich progressive ARCA. We identified 14 patients (nine families) with five different missense or truncating mutations in the aprataxin gene (W279X, A198V, D267G, W279R, IVS5+1), four of which were new. We determined the relative frequency of AOA1 which is 5%. Mutation carriers underwent detailed neurological, neuropsychological, electrophysiological, oculographic and biological examinations, as well as brain imaging. The mean age at onset was 6.8 +/- 4.8 years (range 2-18 years). Cerebellar ataxia with cerebellar atrophy on MRI and severe axonal sensorimotor neuropathy were present in all patients. In contrast, oculomotor apraxia (86%), hypoalbuminaemia (83%) and hypercholesterolaemia (75%) were variable. Choreic movements were frequent at onset (79%), but disappeared in the course of the disease in most cases. However, a remarkably severe and persistent choreic phenotype was associated with one of the mutations (A198V). Cognitive impairment was always present. Ocular saccade initiation was normal, but their duration was increased by the succession of multiple hypometric saccades that could clinically be confused with 'slow saccades'. We emphasize the phenotypic variability over the course of the disease. Cerebellar ataxia and/or chorea predominate at onset, but later on they are often partially masked by severe neuropathy, which is the most typical symptom in young adults. The presence of chorea, sensorimotor neuropathy, oculomotor anomalies, biological abnormalities, cerebellar atrophy on MRI and absence of the Babinski sign can help to distinguish AOA1 from Friedreich's ataxia on a clinical basis. The frequency of chorea at onset suggests that this diagnosis should also be considered in children with chorea who do not carry the IT15 mutation responsible for Huntington's disease.
Mots-clé
Adult Apraxias/*genetics/pathology/psychology Cerebellar Ataxia/*genetics/pathology/psychology Cognition Disorders/etiology DNA-Binding Proteins/genetics Disease Progression Electrooculography Humans Magnetic Resonance Imaging Male Mutation Neuropsychological Tests Nuclear Proteins/genetics Ocular Motility Disorders/*genetics/pathology/psychology Phenotype Sural Nerve/ultrastructure
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 12:43
Dernière modification de la notice
14/02/2022 7:57
Données d'usage