Spinocerebellar Ataxia 27: Clinical Phenotype of Twin Sisters with FGF14 Deletion

Introduction

Spinocerebellar ataxias are neurodegenerative syndromes, with spinocerebellar ataxia type 27 (SCA 27) as a rare cause of ataxia in families. The gene involved in the pathogenesis is the fibroblast-stimulating factor 14 (FGF14) gene. We present two twin sisters with episodic ataxia symptoms triggered by fever, along with a learning disorder (low IQ, memory, and executive functions disturbances). The array-CGH identified a heterozygous interstitial deletion of 424 kb on chromosome 13q33.1 including FGF14 gene associated with SCA 27. This deletion was identified in both twins. It was not possible to study their biological parents (adopted children in a social dystocia context). Their evolution was slow over several years, with development of ataxia, incoordination, tremor, dysarthria, dysmetria, disdiadocinesia, and nystagmus. Magnetic resonance imaging (MRI) study was normal. This case supports previous findings that postulate that alterations in the FGF14 gene include a phenotypic spectrum that includes symptoms of episodic ataxia and learning difficulties. Also, the clinical presentation of both patients supports the hypothesis that this gene regulates the activity in the cerebellum through Nav1.2 and 1.6 α subunits, whose functions appear to be susceptible to fever. The study by array-CGH can help in the diagnosis of neurologic disorders and expand the phenotypic and genotypic spectrum known syndromes, as in the case of SCA27 ([Video 1]).[1] [2] [3] [4] [5]

Video 1

Clinical phenotype of twin patients. Online content including video sequences viewable at: www.thieme-connect.com/products/ejournals/html/10.1055/s-0037-1598110.

• References

• 1 Brusse E, de Koning I, Maat-Kievit A, Oostra BA, Heutink P, van Swieten JC. Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): a new phenotype. Mov Disord 2006; 21 (3) 396-401
• 2 van Swieten JC, Brusse E, de Graaf BM , 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 (1) 191-199 Erratum in: Am J Hum Genet 2003 Apr;72(4):1078
• 3 Coebergh JA, Fransen van de Putte DE, Snoeck IN, Ruivenkamp C, van Haeringen A, Smit LM. A new variable phenotype in spinocerebellar ataxia 27 (SCA 27) caused by a deletion in the FGF14 gene. Eur J Paediatr Neurol 2014; 18 (3) 413-415
• 4 Yan H, Pablo JL, Pitt GS. FGF14 regulates presynaptic Ca2+ channels and synaptic transmission. Cell Reports 2013; 4 (1) 66-75
• 5 Dalski A, Atici J, Kreuz FR, 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 2005; 13 (1) 118-120