Atypical ataxic-spastic syndrome with SYNE1 variant association: Coincidence or contribution?

Abstract

Spinocerebellar ataxias encompass a group of hereditary ataxias notable for their degenerative changes in the cerebellum, brainstem, and spinal cord. This case study details the clinical course of a 42-year-old male presenting with an ataxic-spastic syndrome, harboring a homozygous variant in the SYNE1 gene, classically associated with Autosomal Recessive Spinocerebellar Ataxia type 8 (SCAR8), who also exhibited unusual bilateral thalamic and midbrain hyperintensities. While the significance of this imaging finding remains unclear, it raises the question of whether it represents a rare manifestation of SYNE1-related ataxic-spastic syndrome or an incidental, unrelated observation. The patient's condition deteriorated progressively, characterized by a relevant decline in motor functions and speech articulation, prompting further neurological evaluation and psychomotor rehabilitation. This case underscores the importance of prioritizing detailed clinical assessment while cautiously integrating genetic findings, particularly when variants are of uncertain relevance, in atypical presentations of ataxia. It also highlights the need for continued research into the broader phenotypic spectrum, pathogenic mechanisms, and potential targeted therapies.