Objective: To describe the rare occurrence of coexisting SCA Types 2 and 8 in a pediatric patient.
Background: SCAs are a group of autosomal dominant neurodegenerative diseases characterized by progressive cerebellar dysfunction. As there is a low prevalence in the general population, it is rare to find mutations of two different SCA genes in the same family. SCA2 is characterized by CAG repeats on the cytoplasmic protein ataxin-2 gene (>32 repeats are pathogenic) and SCA8 is characterized by CTA/CTG repeats on overlapping genes ATXN8OS and ATXN8 (sizes of 110-250 most likely to be pathogenic)[1,2].
Method: An 11-year-old male presented with tremors and gait difficulty. He had attention and concentration difficulties starting at age 6. Formal diagnosis of ADHD soon followed, and he continued to demonstrate cognitive and behavioral regression. He had progressive fine motor difficulties, hand tremors, and ataxic gait beginning at age 9. Birth history was reportedly normal and he met all developmental milestones on time. He was adopted, thus family history is unknown. His neurologic exam is significant for difficulty initiating saccadic eye movements, scanning speech, dysmetria, and an intention tremor in bilateral arms. He also had a broad based, ataxic gait with inability to perform tandem gait.
Results: MRI Brain showed cerebellar atrophy. Metabolic workup, microarray, mitochondrial DNA testing, and whole exome sequence analysis was negative. Repeat expansion testing revealed pathogenic expansions in ATXN2 (61/27 repeats), and ATXN8OS (221/24 repeats), both autosomal dominant inheritance. He was diagnosed with SCA2 and SCA8 has started physical, occupational, and speech therapy with modest improvement in symptoms.
Conclusion: SCA8 mutations coexisting with SCA1, SCA3, and SCA6 have been described in several individuals[2-5]. Our patient has a unique combination of gene mutations for SCA2 and SCA8. Coexisting SCA mutations may complicate genetic counseling and clinical prognostication. Our patient’s clinical phenotype of slow saccadic eye movements is more consistent with SCA2, but the other features may be seen in either SCA2 or SCA8. This case, along with other reports of combined SCA gene mutations affords the opportunity to study the interactions of two gene mutations and their effect on clinical expression.
References: 1. Ayhan F, Ikeda Y, Dalton J, Day JW, Ranum LPW. Spinocerebellar ataxia type 8. GeneReviews 2014. 2. Kapur SS, Goldman JG. Two in one: report of a patient with spinocerebellar ataxia types 2 and 10. Arch Neurol 2012;69(9):1200-1203. 3. Izumi Y, Maruyama H, Oda M, Morino H, Okada T, Ito H, Sasaki I, Tanaka H, Komure O, Udaka F, Nakamura S, Kawakami H. SCA8 repeat exapansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6. Am J Hum Genet 2003;72:704-709. 4. Paganoni S, Seelaus C, Ormond KE. Association of spinocerebellar ataxia type 3 and spinocerebellar ataxia type 8 microsatellite expansions: genetic counseling implications. Mov Disord 2008;23(1):154. 5. Sulek A, Hoffman-Zacharska D, Zdzienicka E, Zaremba J. SCA8 repeat expansion coexists with SCA1- not only with SCA6. Am J Hum Genet 2003;73:972-974.
To cite this abstract in AMA style:J. Frey, T. Tholanikunnel, L. Kugelmann, M. Burns, S. Subramony. Spinocerebellar ataxia (SCA) type 2 and type 8: a tale of two repeat expansions in a single patient [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/spinocerebellar-ataxia-sca-type-2-and-type-8-a-tale-of-two-repeat-expansions-in-a-single-patient/. Accessed November 29, 2023.
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