Mutation at the SCA17 locus is not a common cause of primary dystonia.

Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.

Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias.

Primary dystonias represent a clinically and genetically heterogeneous group of movement disorders. Mutations in the epsilon-sarcoglycan (SGCE) gene have been found recently to cause myoclonus-dystonia (MD). Considerable clinical variation of SGCE mutation carriers leads to the hypothesis that mutations in the SGCE gene might also be relevant for other subtypes of dystonias. To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia. Patients with mutations in the DYT1 gene were excluded. We could not detect a mutation in the SGCE gene in any of the 298 patients. Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia.

Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia.

BACKGROUND: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. A 3-base pair (GAG) deletion in the DYT1 gene is held responsible for most cases of early-onset primary generalized dystonia in the Ashkenazi Jewish population as well as in non-Jewish patients. OBJECTIVES: To investigate the prevalence of the GAG deletion in the DYT1 gene and the phenotypic variability in the general population by testing patients with different subtypes of dystonia from 4 different movement disorder outpatient clinics in Germany. METHODS: Two hundred fifty-six patients were tested for the GAG deletion mutation in the DYT1 gene by means of published primers and polymerase chain reaction amplification to determine GAG deletion status. RESULTS: Six of the 256 patients did carry the GAG-deletion in the DYT1 gene. However, only 2 of the 6 mutation carriers presented with what is thought to represent classic features of early-onset primary generalized dystonia. The DYT1 mutation was also detected in 2 patients with multifocal dystonia, 1 of them presenting with involvement of cranial and cervical muscles, and in 2 patients with writer's cramp of both hands with only slight progression. Our findings demonstrate that the mutation may be associated with not only generalized but also segmental and multifocal forms of dystonia. CONCLUSIONS: Our data underline the wide range of phenotypic variability of the DYT1 mutation. A priori prediction of the mutation carrier status in dystonic patients and genetic counseling of affected families with respect to the clinical manifestation may prove difficult.

Low-dose botulinum toxin-a treatment of cervical dystonia - a double-blind, randomized pilot study.

The purpose of the study was to evaluate the clinical efficacy of low-dose botulinum toxin (BTX) treatment of cervical dystonia in a double-blind, randomized pilot study. Thirty-one patients with cervical dystonia and a minimum of 2 previous Dysport treatments received either a mean total target dose of 547 +/- 113 mouse units (MU) (group A, 500 MU Dysport/ml) or a 4-times-diluted preparation 130 +/- 32 MU (group B, 125 MU Dysport/ml). Assessment was made before and 4 weeks after the injection using Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS). Additionally, a self-response scale evaluated the patients' subjective condition for 12 weeks after injection. TWST rating before and after injection revealed comparable clinical improvement in both groups. The severity of cervical dystonia at study entry had no effects on therapeutic effects of either preparation. Self-rating revealed comparable subjective improvement in both groups; however, 3 patients of group B received reinjections due to insufficient effects of the injection. Our findings suggest that low-dose treatment of cervical dystonia with Dysport may be clinically effective during maintenance therapy, at least for a limited period of time. Long-lasting effects of previous Dysport treatments at conventional doses and possibly improved diffusion of a highly diluted toxin preparation may have contributed to the effects of the low-dose regimen. Our data emphasize the need for further studies in order to clearly identify optimal toxin preparations for therapeutic uses of BTX-A in neurologic disorders.