Novel In-Frame FGF14 Deletion Causes Spinocerebellar Ataxia Type 27A: Clinical Response to Deep Brain Stimulation and 4-Aminopyridine.

Abstract

Background: Spinocerebellar ataxia 27A (SCA27A) is a rare neurodegenerative disorder characterized by childhood-onset tremor and progressive cerebellar dysfunction. SCA27A is usually caused by loss-of-function FGF14 variants.

Objectives: We report the identification of a novel FGF14 variant in a five-generation family with autosomal dominant ataxia and describe the clinical phenotype and response to subthalamic nucleus deep brain stimulation (STN-DBS) and 4-aminopyridine (4-AP).

Methods: Whole genome sequencing was performed on the proband, two affected sisters (Patients 2 and 3), and one unaffected sister (III5). Sanger sequencing was performed to confirm the variant and sequence additional family members.

Results: A novel heterozygous in-frame deletion (p.Val119del) in FGF14 was identified in this family affected by childhood-onset tremor followed by late-onset progressive ataxia. Two patients showed significant tremor reduction following STN-DBS and balance improvement with 4-AP.

Conclusions: We identified a novel likely pathogenic FGF14 variant segregating in a family with SCA27A. Additionally, we suggest STN-DBS and 4-AP as promising treatment options for this condition. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.