Late-onset progressive ataxia associated with biallelic expansion of the RFC1 gene: genetically confirmed CANVAS syndrome — case report

Abstract

Case Presentation: A 79-year-old female patient with a history of hypertension presented with chronic cough and a three-year history of progressive imbalance associated with orthostatic dizziness. The condition progressed to marked postural instability and recurrent falls during the past year, resulting in a right forearm fracture. She also reported mild impairment of recent memory. Neurological examination revealed cerebellar ataxia with ataxic gait, dysmetria, and mild dysdiadochokinesia. Distal sensory impairment was present in the lower limbs, including hypoesthesia, reduced vibration sense in a length-dependent gradient pattern, and bilateral Achilles hyporeflexia. Vestibular examination demonstrated vestibular areflexia, with a positive Romberg sign. Electroneuromyography showed symmetric axonal sensory neuropathy, as well as carpal tunnel syndrome and ulnar neuropathy at the elbow. Brain magnetic resonance imaging revealed white matter microangiopathy, Fazekas grade 2. Immunological and paraneoplastic investigations were negative. A genetic panel for ataxias identified a pathogenic biallelic (AAGGG)n repeat expansion in the RFC1 gene, confirming the diagnosis of CANVAS syndrome. Discussion: CANVAS syndrome (Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome) is a neurodegenerative disorder recently associated with a pathogenic biallelic (AAGGG)n repeat expansion in the RFC1 gene. It is characterized by the clinical triad of cerebellar ataxia, sensory neuropathy, and vestibular areflexia. Diagnosis may be challenging in elderly patients with progressive ataxia, as symptoms are often attributed to more prevalent etiologies. Final Comments: This case highlights the importance of considering CANVAS syndrome in the differential diagnosis of late-onset progressive ataxias. Recognition of the characteristic clinical triad and confirmation through genetic analysis are essential for accurate diagnosis, helping to avoid extensive investigations and enabling appropriate patient counseling.