Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites

Department of Neurology, Beth Israel Medical Center, New York, NY, USA.
Neurology (Impact Factor: 8.29). 02/2012; 78(9):649-57. DOI: 10.1212/WNL.0b013e3182494d51
Source: PubMed


To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research.
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.
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 telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies.
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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    • "Laboratory testing reveals an elevated serum alpha-fetoprotein (AFP), sensitivity to ionizing radiation (IR) by colony survival assay, chromosomal translocations, and cell cycle abnormalities (Boder and Sedgwick 1958; Woods and Taylor 1992; Gatti 2001; Sun et al. 2002). We have studied a mutation c.6200C>A (p.A2067D) in the ATM gene that is unique to the Mennonite populations of Canada, Mexico, Central America, Northern Germany, and Netherlands, and is usually associated with dystonia, not ataxia, in young patients (Sandoval et al. 1999; Yanofsky et al. 2009; Saunders-Pullman et al. 2012). The c.6200C>A mutation also appears to be a strong predictor for cancer susceptibility and adverse reactions to radiation or chemotherapy. "
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