RFC1 Spectrum Disorder in a Norwegian CANVAS Cohort.
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| Title: | RFC1 Spectrum Disorder in a Norwegian CANVAS Cohort. |
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| Authors: | Prestsæter, Sjur (AUTHOR), Koht, Jeanette (AUTHOR), Berland, Siren (AUTHOR), Høyer, Helle (AUTHOR), Selmer, Kaja Kristine (AUTHOR), Vedeler, Christian Alexander (AUTHOR), Wedding, Iselin (AUTHOR), Varhaug, Kristin Nielsen (AUTHOR), Carlsen, Trude Morken (AUTHOR), Knappskog, Per (AUTHOR), Rydning, Siri Lynne (AUTHOR), Saleem, Suraiya (AUTHOR) |
| Source: | Acta Neurologica Scandinavica. 5/29/2026, Vol. 2026, p1-7. 7p. |
| Subjects: | Cerebellar ataxia, Genetic profile, Phenotypes, Disease progression, Neurodegeneration, Vestibulo-ocular reflex, Neuropathy, Genes |
| Abstract: | Background: Late‐onset cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive neurodegenerative disorder defined by sensory neuropathy, cerebellar ataxia, and bilateral vestibulopathy. While each symptom impairs balance, their combination causes substantial disability. The most common cause is a biallelic intronic repeat expansion in RFC1, now recognized as a frequent etiology of late‐onset cerebellar ataxia. Objective: The objective of this study is to describe the phenotype, clinical course, and genetic profile of a Norwegian cohort with genetically confirmed CANVAS. Methods: Patients with late‐onset progressive ataxia, without a prior molecular diagnosis, and with at least one additional CANVAS‐associated feature were screened for the RFC1 (AAGGG) repeat expansions. Individuals with confirmed biallelic expansions underwent detailed clinical evaluation. Results: Among the 162 patients tested, 44 (27%) carried biallelic RFC1 expansions. Thirty‐two were clinically assessed, and one additional patient with compound heterozygosity (expansion plus truncating variant) was included. All but one (32/33) exhibited the characteristic triad. Mean age at symptom onset was 50.3 years (range 40–70). All demonstrated additional features beyond the triad, most commonly chronic cough (97%), bulbar dysfunction (85%), and dysautonomia (70%). Limb dystonia, not previously associated with RFC1‐related disease, occurred in two patients (6%). Aspiration pneumonia was the predominant cause of death (7/9, 80%). Conclusion: Our results shed light on the clinical course of CANVAS and expand its phenotypic spectrum. They underscore frequent bulbar dysfunction, dysautonomia, and the risk of aspiration pneumonia, while identifying limb dystonia as a novel manifestation of RFC1‐related disease. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Background: Late‐onset cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive neurodegenerative disorder defined by sensory neuropathy, cerebellar ataxia, and bilateral vestibulopathy. While each symptom impairs balance, their combination causes substantial disability. The most common cause is a biallelic intronic repeat expansion in RFC1, now recognized as a frequent etiology of late‐onset cerebellar ataxia. Objective: The objective of this study is to describe the phenotype, clinical course, and genetic profile of a Norwegian cohort with genetically confirmed CANVAS. Methods: Patients with late‐onset progressive ataxia, without a prior molecular diagnosis, and with at least one additional CANVAS‐associated feature were screened for the RFC1 (AAGGG) repeat expansions. Individuals with confirmed biallelic expansions underwent detailed clinical evaluation. Results: Among the 162 patients tested, 44 (27%) carried biallelic RFC1 expansions. Thirty‐two were clinically assessed, and one additional patient with compound heterozygosity (expansion plus truncating variant) was included. All but one (32/33) exhibited the characteristic triad. Mean age at symptom onset was 50.3 years (range 40–70). All demonstrated additional features beyond the triad, most commonly chronic cough (97%), bulbar dysfunction (85%), and dysautonomia (70%). Limb dystonia, not previously associated with RFC1‐related disease, occurred in two patients (6%). Aspiration pneumonia was the predominant cause of death (7/9, 80%). Conclusion: Our results shed light on the clinical course of CANVAS and expand its phenotypic spectrum. They underscore frequent bulbar dysfunction, dysautonomia, and the risk of aspiration pneumonia, while identifying limb dystonia as a novel manifestation of RFC1‐related disease. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 00016314 |
| DOI: | 10.1155/ane/6613732 |
