Objective: To describe a case of a man with pathogenic repeat expansions in both ATXN3 and ATXN10.

Background: SCA3 is caused by abnormal polyglutamine repeat expansions in ATXN3 and is among the most common forms of spinocerebellar ataxia (SCA). It may present with prominent ataxia in addition to ophthalmoplegia, peripheral neuropathy, and dystonia [1]. SCA10 is caused by abnormal pentanucleotide repeat expansions in ATXN10 and may present with seizures in addition to ataxia. It has been described primarily in individuals with Mexican and Brazilian heritage [2]. Rare cases of individuals with two combined forms of SCA have been reported [3]. To our knowledge, this is the first report of combined SCA3 and SCA10.

Method: A 23 year-old man with Mexican and Puerto-Rican ancestry presented for evaluation at Mount Sinai Beth Israel for an 8 year history of progressive neurologic symptoms with no known neurologic family history. He had normal cognitive and motor milestones but mild learning difficulties in elementary school. At age 15 he began to fall. MRI brain was unremarkable. By age 19 he had dysarthria, saccadic visual pursuit, dystonic posturing in the right hand, limb spasticity, and worsened gait instability. Chromosome analysis and microarray were unrevealing. By age 21 he was wheelchair bound and had progressive cognitive decline. He developed generalized dystonia. Whole exome sequencing was unrevealing. At age 23 exam showed marked cognitive impairment, dysarthria, and impaired supraduction. He had generalized dystonia affecting face, neck, trunk, and extremities. He had mild distal weakness in the upper extremities and spasticity in all limbs with sustained ankle clonus. He had marked limb dysmetria and profound gait ataxia with inability to stand without full assistance. Serum testing for repeat expansions associated with ataxia was performed.

Results: He was found to have 1911 and 12 repeats in ATXN10 alleles (Normal </=22, Positive >/=700) and 82 and 29 repeats in ATXN3 alleles (Normal </=40, Positive >/=53). He recently relocated to California and established care at UCSF. He has had modest benefit to dystonia with baclofen, clonazepam, and botulinum toxin injections to finger and wrist flexors.

Conclusion: We report the unique occurrence of combined SCA3 and SCA10 resulting in a syndrome of dystonia, spasticity, ataxia, and cognitive decline.

References: 1.) Nunes, M. B., Martinez, A. R. M., Rezende, T. J. R., Friedman, J. H., Lopes-Cendes, I., D’Abreu, A., & França Jr, M. C. (2015). Dystonia in Machado–Joseph disease: Clinical profile, therapy and anatomical basis. Parkinsonism & related disorders, 21(12), 1441-1447. 2.) Nunes, M. B., Martinez, A. R. M., Rezende, T. J. R., Friedman, J. H., Lopes-Cendes, I., D’Abreu, A., & França Jr, M. C. (2015). Dystonia in Machado–Joseph disease: Clinical profile, therapy and anatomical basis. Parkinsonism & related disorders, 21(12), 1441-1447. 3.) Baizabal‐Carvallo, J. F., Xia, G., Botros, P., Laguna, J., Ashizawa, T., & Jankovic, J. (2015). Bolivian kindred with combined spinocerebellar ataxia types 2 and 10. Acta Neurologica Scandinavica, 132(2), 139-142.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/concurrent-sca3-and-sca10-in-a-young-man-with-ataxia-and-prominent-dystonia/