Objective: We describe a unique case of a 68-year-old man with chronic ataxia, spasmodic cough, neuropathy and hearing loss who was initially felt to have mitochondrial disorder despite inconclusive workup. He was later given the diagnosis of CANVAS after genetic confirmation.

Background: Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome (CANVAS) is an underdiagnosed cause of late-onset hereditary ataxia that emerged in the past 30 years. Besides the classic triad of ataxia, neuronopathy, and vestibulopathy patients often have chronic cough, signs of dysautonomia, and neurogenic pain.

Method: Upon retrospective chart review, this patient’s symptoms started when he was 50 years old. His initial symptoms include bilateral lower extremity numbness that progressively worsened over the years and resulted in gait and balance difficulties. He developed progressive sequential hearing loss in both ears after 10 years. His initial workup with electro-diagnostic testing was consistent with sensory neuropathy and a genetic neuropathy panel revealed heterozygous pathogenic mutation of the POLG gene, however, he does not fit the classic phenotype of autosomal recessive progressive sclerosing poliodystrophy associated with this mutation. variants of unknown significance in KIF1A and NDRG1 were also noted.  He was started on treatment for a presumed mitochondrial disorder without clinical improvement.

Results: Upon further inquiry, patient reported falls, dizziness, clumsiness, dysphagia to solids and lifelong chronic cough. His exam as seen in video was consistent with bilateral hearing loss, dysarthria, diffuse sensory impairment in all modalities in bilateral lower extremities, positive Romberg test, diffuse areflexia, and ataxia. Later a single gene testing for RFC 1 mutation, based on the combination of neuropathy, ataxia, and chronic cough, demonstrated a biallelic pathogenic expansion confirming CANVAS syndrome.

Conclusion: We emphasize the importance of expanding genetic testing to include the RFC1 gene in cases of ataxia, neuropathy, and chronic spasmodic cough with unyielding workup, as CANVAS is an under-diagnosed novel genetic disease that is not covered by routine sponsored gene panels. Accurate history, exam could aid in deciding appropriate genetic testing that would reduce unwanted costs for the patient.

References: Dupré, M., Hermann, R., & Froment Tilikete, C. (2021). Update on Cerebellar Ataxia with Neuropathy and Bilateral Vestibular Areflexia Syndrome (CANVAS). Cerebellum (London, England), 20(5), 687–700. https://doi.org/10.1007/s12311-020-01192-w

Szmulewicz, D. J., McLean, C. A., Rodriguez, M. L., Chancellor, A. M., Mossman, S., Lamont, D., Roberts, L., Storey, E., & Halmagyi, G. M. (2014). Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS. Neurology, 82(16), 1410–1415. https://doi.org/10.1212/WNL.0000000000000352

Szmulewicz, D. J., Roberts, L., McLean, C. A., MacDougall, H. G., Halmagyi, G. M., & Storey, E. (2016). Proposed diagnostic criteria for cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Neurology. Clinical practice, 6(1), 61–68. https://doi.org/10.1212/CPJ.0000000000000215

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