Objective: The objective is to investigate the genetic basis of cerebellar ataxia and identify a novel variant associated with this condition in an active-duty military member.

Background: The idea that a single gene can manifest a specific phenotype is often challenged due to the apparent pleiotropy many genes exhibit. The SPTAN1 gene is known to encode αII spectrin, a scaffolding protein that plays an important role in the membrane integrity of myelinated axons and synaptogenesis. Pathologic mutations in SPTAN1 have resulted in various neurologic manifestations from epileptic encephalopathy to ataxia and spastic paraplegia. Recent studies discuss a variety of de novo and inherited SPTAN1 variants causing both pure and complex cerebellar ataxia phenotypes in 22 patients from 14 families. We report a novel loss-of-function de novo mutation in SPTAN1 in a young male with evident cerebellar ataxia.

Method: N/A

Results: A 34-year-old active-duty Navy male, with Hispanic heritage and no family history of neurologic problems, was evaluated for adult-onset tremors and clumsiness that have been progressively worsening over 5 years. The patient reports involuntary episodes of truncal tremulousness and lower limb movements that affect his gait. The patient reports normal upbringing and developmental milestones and has no evidence of intellectual disability. He participated in martial arts, cross country, and wrestling throughout high school without difficulty. On exam, the patient had dysmetria on heel-to-shin and difficulty with tandem gait. The patient’s Scale for the Assessment and Rating of Ataxia (SARA) score was 10. On MRI brain, the patient had marked atrophy of the cerebellum. Genetic testing revealed likely pathogenic heterozygous mutation c.2158C>G (p.His720Asp) in the SPTAN1 gene, likely a de novo variant given that it was not detected in his asymptomatic parents with concurrent genetic testing.

Conclusion: SPTAN1 is known to be a very rare cause of cerebellar ataxia with pathogenesis impairing myelin stability. Our case reports a novel variant in the SPTAN1 gene. Screening of SPTAN1 variants should be considered in young patients with evidence of mild-moderate cerebellar ataxia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-sptan1-variant-in-adult-onset-cerebellar-ataxia-in-active-duty-military-member/