SCA27 is a cause of early-onset ataxia and developmental delay

Abstract

Spinocerebellar ataxias (SCA) refer to rare neurodegenerative inherited disorders which constitute a highly heterogeneous group of autosomal dominant cerebellar ataxias. 1 Schöls L. Bauer P. Schmidt T. Schulte T. Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004; 3: 291-304 Abstract Full Text Full Text PDF PubMed Scopus (796) Google Scholar Typically, SCA have an adult-onset and the prevalence is low, about 0.3–2 per 100,000. 1 Schöls L. Bauer P. Schmidt T. Schulte T. Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004; 3: 291-304 Abstract Full Text Full Text PDF PubMed Scopus (796) Google Scholar , 2 Rossi M. Perez-Lloret S. Doldan L. Cerquetti D. Balej J. Millar Vernetti P. et al. Autosomal dominant cerebellar ataxias: a systematic review of clinical features. Eur J Neurol Off J Eur Fed Neurol Soc. 2014; 21: 607-615 PubMed Google Scholar Mutations in the FGF14 gene are responsible for SCA27, a rare cause of SCA initially described in a large Dutch family with 14 affected relatives. 3 Van Swieten J.C. Brusse E. de Graaf B.M. Krieger E. van de Graaf R. de Koning I. et al. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet. 2003; 72: 191-199 Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar A total of six SCA27 families have been reported to date, with a median age of onset of 28 years. 3 Van Swieten J.C. Brusse E. de Graaf B.M. Krieger E. van de Graaf R. de Koning I. et al. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet. 2003; 72: 191-199 Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar , 4 Brusse E. de Koning I. Maat-Kievit A. Oostra B.A. Heutink P. van Swieten J.C. Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): a new phenotype. Mov Disord Off J Mov Disord Soc. 2006; 21: 396-401 Crossref PubMed Scopus (86) Google Scholar , 5 Dalski A. Atici J. Kreuz F.R. Hellenbroich Y. Schwinger E. Zühlke C. Mutation analysis in the fibroblast growth factor 14 gene: frameshift mutation and polymorphisms in patients with inherited ataxias. Eur J Hum Genet EJHG. 2005; 13: 118-120 Crossref PubMed Scopus (77) Google Scholar , 6 Misceo D. Fannemel M. Barøy T. Roberto R. Tvedt B. Jaeger T. et al. SCA27 caused by a chromosome translocation: further delineation of the phenotype. Neurogenetics. 2009; 10: 371-374 Crossref PubMed Scopus (33) Google Scholar , 7 Shimojima K. Okumura A. Natsume J. Aiba K. Kurahashi H. Kubota T. et al. Spinocerebellar ataxias type 27 derived from a disruption of the fibroblast growth factor 14 gene with mimicking phenotype of paroxysmal non-kinesigenic dyskinesia. Brain Dev. 2012; 34: 230-233 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar , 8 Coebergh J.A. Fransen van de Putte D.E. Snoeck I.N. Ruivenkamp C. van Haeringen A. Smit L.M. A new variable phenotype in spinocerebellar ataxia 27 (SCA 27) caused by a deletion in the FGF14 gene. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2014; 18: 413-415 Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar Recently, Coebergh et al. 8 Coebergh J.A. Fransen van de Putte D.E. Snoeck I.N. Ruivenkamp C. van Haeringen A. Smit L.M. A new variable phenotype in spinocerebellar ataxia 27 (SCA 27) caused by a deletion in the FGF14 gene. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2014; 18: 413-415 Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar described in this journal a new SCA27 family caused by the first intragenic deletion identified in FGF14, spanning the first four exons. Interestingly, a highly variable expression of the disease was observed. The index case displayed a severe early-onset ataxia and delayed motor skills, although her mother, who also carried the deletion, suffered from a classical form of adult ataxia. The authors concluded to phenotypic variability with apparent complete penetrance. Similarly, a young girl carrier of a translocation disrupting the FGF14 gene was described with psychomotor delay, small occipito-frontal circumference (OFC) since birth and progressive moderate to severe ataxia at age 5.5 years. 6 Misceo D. Fannemel M. Barøy T. Roberto R. Tvedt B. Jaeger T. et al. SCA27 caused by a chromosome translocation: further delineation of the phenotype. Neurogenetics. 2009; 10: 371-374 Crossref PubMed Scopus (33) Google Scholar Her mother shared the same translocation and presented seizures during childhood, learning difficulties, and a mild cerebellar atrophy on examination at age 42 years.