Abstract
Spinocerebellar ataxia type 2 (SCA2) is a late-onset autosomal dominant cerebellar ataxia caused by triplet CAG/CTG expansion in the ATX2 gene. The initial symptoms usually appear when subjects are in their 30s. Pediatric onset is less common and usually associated with larger triplet expansions. We here report the case of a 1-year-old girl who presented with facial dysmorphism, dystonic features, developmental delay, and retinitis pigmentosa. She was diagnosed as carrying an expanded CAG/CTG tract (92 repeats) before a molecular diagnosis of SCA2 was made in her father. Facial dysmorphism associated with developmental delay and retinitis pigmentosa in early childhood should prompt a careful family investigation for ataxia and study of ATX2.
References
Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet. 1983;21(1):1151–5.
Geschwind DH, Perlman S, Figueroa CP, et al. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet. 1997;60(4):842–50.
Durr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol. 2010;9(9):885–94.
Velázquez-Pérez L, Rodríguez-Labrada R, García-Rodríguez JC, Almaguer-Mederos LE, Cruz-Mariño T, Laffita-Mesa JM. A comprehensive review of spinocerebellar ataxia type 2 in Cuba. Cerebellum. 2011;10(2):184–98.
Pulst SM, Nechiporuk A, Nechiporuk T, et al. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet. 1996;14(3):269–76.
La Spada AR, Paulson HL, Fischbeck KH. Trinucleotide repeat expansion in neurological disease. Ann Neurol. 1994;36(6):814–22.
Dueñas AM, Goold R, Giunti P. Molecular pathogenesis of spinocerebellar ataxias. Brain. 2006;129(Pt 6):1357–70.
Ramos EM, Martins S, Alonso I, et al. Common origin of pure and interrupted repeat expansions in spinocerebellar ataxia type 2 (SCA2). Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):524–31.
Sakamoto N, Larson JE, Iyer RR, et al. GGA*TCC-interrupted triplets in long GAA*TTC repeats inhibit the formation of triplex and sticky DNA structures, alleviate transcription inhibition, and reduce genetic instabilities. J Biol Chem. 2001;276(29):27178–87.
Stevanin G, Dürr A, Brice A. Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology. Eur J Hum Genet. 2000;8(1):4–18.
Pearson CE, Nichol Edamura K, Cleary JD. Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet. 2005;6(10):729–42.
Babovic-Vuksanovic D, Snow K, Patterson MC, Michels VV. Spinocerebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat expansion. Am J Med Genet. 1998;79(5):383–7.
Moretti P, Blazo M, Garcia L, et al. Spinocerebellar ataxia type 2(SCA2) presenting with ophthalmoplegia and developmental delay in infancy. Am J Med Genet. 2004;124A(4):392–6.
Mao R, Aylsworth AS, Potter N, et al. Childhood onset ataxia: testing for large CAG repeats in SCA2 and SCA7. Am J Med Genet. 2002;110(4):338–45.
Abdel-Aleem A, Zaki MS. Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy. J Neurol. 2008;255(3):413–9.
Cagnoli C, Stevanin G, Michielotto C, et al. Large pathogenic expansions in the SCA2 and SCA7 genes can be detected by fluorescent repeat-primed polymerase chain reaction assay. J Mol Diagn. 2006;8(1):128–32.
Jacobi H, Bauer P, Giunti P, et al. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology. 2011. doi:10.1212/WNL.0b013e31822e7ca0.
Whaley NR, Fujioka S, Wszolek ZK. Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis. 2011;6:33.
Ramocki MB, Chapieski L, McDonald RO, Fernandez F, Malphrus AD. Spinocerebellar ataxia type 2 presenting with cognitive regression in childhood. J Child Neurol. 2008;23(9):999–1001.
Benton CS, de Silva R, Rutledge SL, et al. Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype. Neurology. 1998;51(4):1081–6.
Acknowledgments
We thank Mrs. Catherine Wrenn for her valuable help in the English writing.
Conflict of interests
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Di Fabio, R., Santorelli, F., Bertini, E. et al. Infantile Childhood Onset of Spinocerebellar Ataxia Type 2. Cerebellum 11, 526–530 (2012). https://doi.org/10.1007/s12311-011-0315-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12311-011-0315-9