Objective: To present what might be a new phenotype of spinocerebellar ataxia type 45.

Background: Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominant, adult-onset neurodegenerative disorders presenting with progressive cerebellar ataxia. With the advent of genetic testing, several new genes have been identified and currently there are 48 subtypes of SCAs described. SCA45 was first reported in 2017 after a WES-based study and, to our knowledge, there are only two families and one sporadic case described.

Method: Case report.

Results: A 75-year-old caucasian female, with unremarkable family history, presented in 2016 complaining of several episodes of falls due progressive gait impairment. In the first visit, neurologic examination revealed spastic paraparesis with bilateral extensor plantar responses, generalized chorea and a pancerebellar syndrome. Neuroaxis MRI only revealed diffuse cerebral and cerebellar atrophy. Blood work for acquired ataxia and chorea aetiologies was unremarkable. Given the exuberant choreiform movements, genetic testing for Huntington’s disease, its main phenocopies and SCA 1,2,3,6,7 were ordered first, which revealed no mutations. Next a NGS panel for dominant and X-linked ataxias revealed an heterozygous missense variant in FAT2 gene, of unknown significance. Currently, the patient is on a wheelchair, maintains a pancerebellar involvement and has developed spastic tetraparesis with no signs of involvement of lower motor neurons, alongside severe dysphagia; the choreiform movements resolved with tetrabenazine 25mg/day.

Conclusion: This patient presented with a complex phenotype characterized by generalized chorea, cerebellar ataxia and upper motor neuron signs. Given the occam’s razor principle, we would be tempted to explain all the symptoms with this mutation. However, all SCA45 cases described so far presented with a late onset pure cerebellar ataxia. We believe that at least the cerebellar symptoms can be accounted by this genetic mutation. After discussion with the genetics team, WES will be ordered. As the patient has no family members, segregation studies are impossible to perform.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/generalized-chorea-cerebellar-ataxia-and-spastic-tetraparesis-with-a-genetic-mutation-in-fat2-gene-coincidence-or-a-new-sca45-phenotype/