Expanding the Landscape of Spinocerebellar Ataxia Type 5

Abstract

Spinocerebellar ataxia type 5 (SCA5) is a rare subtype of SCA that usually affects adults. It has been recently reported in children in Europe, North America, and China. This study aims to describe clinical, radiological, and genetic data of a child presenting with SCA5, caused by a heterozygous likely pathogenic missense variant in SPTBN2 (NM_006946.3: c.1052G > C, p.Arg351Pro). According to databases and a review of the literature, this is one of few cases of SCA5 from Latin America. Expanding the landscape of SCA5 is relevant to the differential diagnosis of ataxic cerebral palsy and the autosomal recessive cerebellar ataxias.

Keywords

spinocerebellar ataxia - hypotonia - developmental delay - genetics

• References

• 1 Dick KA, Ikeda Y, Day JW, Ranum LPW. Spinocerebellar ataxia type 5. Handb Clin Neurol 2012; 103: 451-459
• 2 Romaniello R, Citterio A, Panzeri E. et al. Novel SPTBN2 gene mutation and first intragenic deletion in early onset spinocerebellar ataxia type 5. Ann Clin Transl Neurol 2021; 8 (04) 956-963
• 3 Accogli A, St-Onge J, Addour-Boudrahem N. et al. Heterozygous missense pathogenic variants within the second spectrin repeat of SPTBN2 lead to infantile-onset cerebellar ataxia. J Child Neurol 2020; 35 (02) 106-110
• 4 Nicita F, Nardella M, Bellacchio E. et al. Heterozygous missense variants of SPTBN2 are a frequent cause of congenital cerebellar ataxia. Clin Genet 2019; 96 (02) 169-175
• 5 Gouvêa LA, Raslan IR, Rosa ABR. et al. Spinocerebellar ataxia type 5 (SCA5) mimicking cerebral palsy: a very early onset autosomal dominant hereditary ataxia. Cerebellum 2022;
• 6 Brunet T, Jech R, Brugger M. et al. De novo variants in neurodevelopmental disorders-experiences from a tertiary care center. Clin Genet 2021; 100 (01) 14-28
• 7 Richards S, Aziz N, Bale S. et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17 (05) 405-424
• 8 Zonta A, Brussino A, Dentelli P, Brusco A. A novel case of congenital spinocerebellar ataxia 5: further support for a specific phenotype associated with the p.(Arg480Trp) variant in SPTBN2 . BMJ Case Rep 2020; 13 (12) e238108
• 9 Scott SSO, Pedroso JL, Barsottini OGP, França-Junior MC, Braga-Neto P. Natural history and epidemiology of the spinocerebellar ataxias: insights from the first description to nowadays. J Neurol Sci 2020; 417: 117082
• 10 da Graça FF, Peluzzo TM, Bonadia LC. et al. Diagnostic yield of whole exome sequencing for adults with ataxia: a Brazilian perspective. Cerebellum 2022; 21 (01) 49-54