Abstract Details

Title Young-Adulthood Onset Chronic Cough as a Three Decades Prodrome of RFC1-related Autonomic and Sensory Neuropathy

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:00 PM-6:00 PM)

Poster/Presentation
Number 9-016

Objective To inform about CANVAS, a rare overlooked progressive neurodegenerative disorder with various clinical and genetic phenotypes.

Background RFC1-related disease spans a spectrum from full cerebellar ataxia-neuropathy-vestibular areflexia syndrome (CANVAS) to isolated sensory or autonomic neuropathy. CANVAS is due to AAGGG repeat expansion in the second intron of replication factor-C subunit-1 (RFC1) gene. In addition to autonomic dysfunction symptoms as the most prevalent, sensory neuropathy/neuronopathy manifestations with/without overt vestibular dysfunction vary in presentation and severity. Two-thirds of affected individuals report a dry spasmodic cough that may antedate neurologic signs by decades, yet the link is often missed, highlighting cough as an overlooked prodrome.

Design/Methods

Searched PubMed literature (2000–2025) for RFC1-disease.

Results A 57-year-old woman had a refractory dry cough from young adulthood. In her 5^th decade she developed cold feet with paraesthesias, unsteady gait and orthostatic light-headedness. Examination with length-dependent loss of light touch, vibration and proprioception. Autonomic review revealed heat intolerance, anhidrosis and mottled acral skin. Nerve-conduction studies demonstrated absent SNAPs in legs and reduced in arms consistent with sensory neuronopathy. Brain-MRI demonstrated mild parenchymal atrophy and nonspecific periventricular FLAIR-hyperintensities without cerebellar tonsillar descent. Repeat-primed PCR detected biallelic RFC1 AAGGG expansions, establishing an RFC1-related disorder in the spectrum of CANVAS. Chronic cough was therefore recognized as the inaugural symptom, preceding neuropathy by three decades.

Conclusions Refractory chronic cough can represent the sole manifestation of CANVAS for decades. Autonomic dysfunction may be related to a ganglioneuropathy. There is no specific treatment. Neurologists should query for a lifetime chronic cough in late-onset neuropathy even without overt vestibular involvement. Timely recognition enables targeted genetic testing, counselling, appropriate management of symptoms and avoidance of unnecessary immunotherapies. Genetic testing with repeat-primed PCR to detect intronic expansions in RFC1 should be performed in cases with suspicion of CANVAS and/or in case of whole-exome sequencing negative hereditary sensory and autonomic neuropathy.

Authors/Disclosures
Kyle R. Marden, MD (Northwestern Medicine) PRESENTER	Dr. Marden has nothing to disclose.
Goran Rakocevic, MD, FAAN (Thomas Jefferson University)	Dr. Rakocevic has nothing to disclose.

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