Spinocerebellar ataxia 27B (SCA27B)-a systematic review and a case report of a Polish family

Abstract

Dominantly inherited GAA repeat expansions in the FGF14 gene have recently been identified as the cause of spinocerebellar ataxia 27B (SCA27B). Our study focused on a Polish patient case along with asymptomatic family members. Moreover, we systematically reviewed available case reports to better understand the SCA27B phenotype. Genetic tests for SCA27B were performed on genomic DNA isolated from blood. Long-range polymerase chain reaction (LR-PCR) followed by Nanopore sequencing was conducted to establish the number of GAA repeats. The available literature was systematically reviewed per the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The patient's genetic studies identified pure expansions of (GAA) 420/94 repeats in FGF14, confirming the SCA27B diagnosis. A systematic review of 815 cases provides further insight into the typical clinical presentation, with gait ataxia (95.96%) being the most prevalent symptom, followed by abnormal saccadic pursuits (80.69%), nystagmus (71.15%), diplopia (54.05%), and dysarthria (51.22%). Notably, 41.87% of cases exhibited episodic symptoms. The correlation between GAA repeat expansions and the pathogenesis of SCA27B requires further studies. The unique course of the disease with episodic symptoms may cause diagnostic difficulties. Due to its high prevalence in the European population, SCA27B should be considered when diagnosing the causes of late-onset cerebellar ataxia.

Keywords: FGF14; Downbeat nystagmus; GAA repeats; LOCA; SCA27B.

Fig. 1

A—brain MRI (T1 W sagittal) of a healthy man at the age of 64 y, B—brain MRI (T1 W sagittal) of the Polish patient with GAA repeat expansions in FGF14 at the age of 64 y. Slight atrophy of the cerebellum is observed (the primary, secondary, and prepyramidal fissures are open, and a more prominent quadrigeminal cistern is also present)

Fig. 2

The pedigree of the family affected by SCA27B. Symptomatic proband carries a pathological number of 420 GAA repeats in one allele, which undergoes substantial contraction when transmitted to his son. The shorter paternal allele inherited by the daughter also underwent contraction. The mother is homozygous regarding the GAA repeat number and passes her FGF14 alleles to the offspring with no change in repeat size. The alleles with GAA expansions are marked in red. The presented GAA repeats number was established by Nanopore sequencing