Dr. Stamelou and Dr. Charlesworth contributed equally to the study.
The phenotypic spectrum of DYT24 due to ANO3 mutations
Article first published online: 17 JAN 2014
© 2014 The Authors. Movement Disorders published by International Parkinson and Movement Disorder Society
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 29, Issue 7, pages 928–934, June 2014
How to Cite
Stamelou, M., Charlesworth, G., Cordivari, C., Schneider, S. A., Kägi, G., Sheerin, U.-M., Rubio-Agusti, I., Batla, A., Houlden, H., Wood, N. W. and Bhatia, K. P. (2014), The phenotypic spectrum of DYT24 due to ANO3 mutations. Mov. Disord., 29: 928–934. doi: 10.1002/mds.25802
Full financial disclosures and author roles may be found in the online version of this article.
Funding agencies: DNA extraction work was undertaken at University College London Hospitals, University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centers funding scheme.
Relevant conflicts of interest/financial disclosures: Nothing to report.
- Issue published online: 12 JUN 2014
- Article first published online: 17 JAN 2014
- Manuscript Accepted: 9 DEC 2013
- Manuscript Revised: 14 NOV 2013
- Manuscript Received: 13 DEC 2012
- cervical dystonia;
- cranial dystonia;
- laryngeal dystonia;
- dystonic tremor;
Genes causing primary dystonia are rare. Recently, pathogenic mutations in the anoctamin 3 gene (ANO3) have been identified to cause autosomal dominant craniocervical dystonia and have been assigned to the dystonia locus dystonia-24 (DYT24). Here, we expand on the phenotypic spectrum of DYT24 and provide demonstrative videos. Moreover, tremor recordings were performed, and back-averaged electroencephalography, sensory evoked potentials, and C-reflex studies were carried out in two individuals who carried two different mutations in ANO3. Ten patients from three families are described. The age at onset ranged from early childhood to the forties. Cervical dystonia was the most common site of onset followed by laryngeal dystonia. The characteristic feature in all affected individuals was the presence of tremor, which contrasts DYT24 from the typical DYT6 phenotype. Tremor was the sole initial manifestation in some individuals with ANO3 mutations, leading to misdiagnosis as essential tremor. Electrophysiology in two patients with two different mutations showed co-contraction of antagonist muscles, confirming dystonia, and a 6-Hz arm tremor at rest, which increased in amplitude during action. In one of the studied patients, clinically superimposed myoclonus was observed. The duration of the myoclonus was in the range of 250 msec at about 3 Hz, which is more consistent with subcortical myoclonus. In summary, ANO3 causes a varied phenotype of young-onset or adult-onset craniocervical dystonia with tremor and/or myoclonic jerks. Patients with familial cervical dystonia who also have myoclonus-dystonia as well as patients with prominent tremor and mild dystonia should be tested for ANO3 mutations. © 2014 The Authors. Movement Disorders published by International Parkinson and Movement Disorder Society