Objective: First case report to demonstrate an overlap of two autosomal dominant ataxia’s (SCA8 and SCA14) in same patient expanding the clinical spectrum of spinocerebellar ataxia syndromes.

Background: SCA14 is caused by mutations in the protein kinase C gamma (PKCγ, PRKCG) gene. The pathogenesis of SCA8 involves a (CAG)n repeat in ATXN8. Genetic testing, demonstrating a triplet repeat expansion of the SCA8 gene on chromosome 13q21, has been critical in confirming the diagnosis of SCA8 [1]. Cases has been encountered in the past where SCA8 may rarely coexist with SCA6 [2] or SCA1 [3] but no case report to date available of its coexistence with SCA14. In previous reports there are many overlapping clinical sign’s have mentioned for both ataxia syndromes (Tremor, myoclonus, ataxia and cerebellar atrophy).

Method: 21 year old right handed man patient presented with 2 year history of intermittent muscle twitches, headache’s and tremors. He noted to have head tremor with mild abnormal head posture. There was mild ataxia and difficulty with tandem walking. Patient noted to have hyperreflexia on examination. Brain MRI without contrast demonstrated marked volume loss involving the cerebellar hemispheres and vermis which was advanced for patient’s chronological age.

Results: Comprehensive Athena diagnostic Ataxia Panel of tests identified a variant of uncertain clinical significance (VUS), SCA14 (PRKCG) C:362_379 18 bp duplication. Additionally patient possesses a borderline repeat expansion in the ATXN8OS gene (SCA8).
ATXN8OS [69 and 21 repeats]
PRKCG c.362_379: 18bp. Duplication; Codon: 121-127 [Heterozygous mRNA reading frame maintained]

Conclusion: First case report of coexistence of two autosomal dominant ataxia syndromes (SCA8 and SCA14). Our patient shown sign’s of muscle twitches (myoclonus), head tremor and difficulty with tandem walking which has also been seen previously in both types ataxia’s. Cerebellar atrophy on brain MRI seen in our patient has also been reported previously in SCA8 and SCA14 patients. However abnormal posture of head in our patient indicating cervical dystonia has not been previously reported in either of ataxia syndromes and could be result coexistence of both pathogenic genes mutations.

References: [1] Koob MD, Moseley ML, Schut LJ, Benzow KA, Bird TD, Day JW, et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 1999;21:379–84. [2] Izumi Y, Maruyama H, Oda M, Morino H, Okada T, Ito H, et al. SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6. Am J Hum Genet 2003;72:704–9. [3] Sulek A, Hoffman-Zacharska D, Zdzienicka E, Zaremba J. SCA8 repeat expansion coexists with SCA1–not only with SCA6. Am J Hum Genet 2003;73:972–4.

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-presentation-of-coexistence-of-spinocerebellar-ataxia-sca14-gene-duplication-variant-in-association-with-spinocerebellar-ataxia-sca8-gene-mutation-in-a-same-patient/