Pearls & Oy-sters: ATX-FGF14 Mimicking Autoimmune Pathology.

Area of Science:

• Neurogenetics
• Autosomal dominant disorders
• Genetic neurology

Background:

• Autosomal dominant spinocerebellar ataxia 27 (ATX-FGF14) is caused by pathogenic variants in the fibroblast growth factor 14 (FGF14) gene.
• Variable phenotypic expression often complicates diagnosis, particularly in patients lacking a known family history.

Observation:

• Two cases of ATX-FGF14 within a single family presented with episodic neurological symptoms, initially raising suspicion for autoimmune etiologies.
• Both patients exhibited coexistent systemic autoimmunity and lacked cerebellar or brainstem volume loss, further complicating initial diagnostic assessments.
• Initial evaluations revealed limited family history, underscoring the challenge in early diagnosis without comprehensive genetic and familial information.

Findings:

• Genetic testing confirmed a pathogenic structural variant in the FGF14 gene in both affected family members, establishing the diagnosis of ATX-FGF14.
• The study identified a pathogenic structural variant in the FGF14 gene, confirming ATX-FGF14 in both patients.

Implications:

• Highlights the critical importance of obtaining detailed interval family histories during patient follow-ups for undiagnosed adult neurological conditions.
• Emphasizes the need for objective analysis of immunotherapy trials to prevent unnecessary treatments when diagnosing neurogenetic disorders.
• Underscores the necessity of genetic testing for accurate diagnosis of ATX-FGF14, especially when clinical presentations mimic autoimmune neurological diseases.