TY - JOUR
T1 - Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites
AU - Saunders-Pullman, R.
AU - Raymond, D.
AU - Stoessl, A. J.
AU - Hobson, D.
AU - Nakamura, T.
AU - Pullman, S.
AU - Lefton, D.
AU - Okun, M. S.
AU - Uitti, R.
AU - Sachdev, R.
AU - Stanley, K.
AU - San Luciano, M.
AU - Hagenah, J.
AU - Gatti, R.
AU - Ozelius, L. J.
AU - Bressman, S. B.
N1 - Funding Information:
Study funding: Supported by NIH (NS26636 to S.B.B., K23NS047256 to R.S.-P.) , the Bachmann-Strauss Dystonia & Parkinson Foundation, and the Parkinson's Disease Foundation (to S.P.).
PY - 2012/2/28
Y1 - 2012/2/28
N2 - Objective: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. Methods: Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. Result: Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangi-ectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. Conclusion: Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.
AB - Objective: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. Methods: Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. Result: Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangi-ectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. Conclusion: Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.
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U2 - 10.1212/WNL.0b013e3182494d51
DO - 10.1212/WNL.0b013e3182494d51
M3 - Article
C2 - 22345219
AN - SCOPUS:84863267494
SN - 0028-3878
VL - 78
SP - 649
EP - 657
JO - Neurology
JF - Neurology
IS - 9
ER -