Spectrum disorder of RFC1 expansions/CANVAS: Clinical and electrophysiological characterization of a group of 31 patients

Abstract

Introduction/Objective

Biallelic expansion of the pentanucleotide AAGGG in the RFC1- gene is associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to comprehensively characterise this condition by conducting an in-depth neurophysiological examination of afflicted patients.

Methods

A retrospective analysis was conducted in 31 RFC1-positive patients. Assessment included clinical examination and electrodiagnostic tests: nerve conduction studies, F waves, needle electromyography, H, blink and masseter reflexes; Autonomic Nervous System (ANS): Heart Rate Variability, Sympathetic Skin Response and Electrochemical Skin Conductance, and Quantitative Sensory Test (QST). Medullar tracts were assessed using Somatosensory Evoked Potentials (SEPs) and Transcranial Magnetic Stimulation.

Results

All patients exhibited moderate to severe sensory axonal neuropathy/neuronopathy, whereas motor nerve conduction parameters and the pyramidal pathway showed no abnormalities. Tibial nerve SEPs were absent or severely attenuated in all patients, and were moderately affected by the median nerve. H-reflexes were preserved in 85.7% and blink reflex in 60% of tested patients. ANS tests yielded predominantly normal results, although 74% demonstrated impaired QST.

Conclusions

Our findings highlight the characteristic features of sensory neuropathy/neuronopathy and severe somatosensory deficits, with predominantly preserved H-reflexes and motor sparing. Thermoalgesic fibres are frequently involved, whereas the ANS is relatively preserved.

Significance

Neurophysiological examinations can objectively characterize the spectrum of RFC1-related disease.