Research Papers
RFC1-Related Disorders
RFC1-related disorders should be suspected in individuals with onset after age 25 years of one or more of the following clinical findings with supportive electrodiagnostic, vestibular, and imaging findings as well as family history.
Common neurologic findings
Sensory neuropathy or neuronopathy
Bilateral vestibulopathy
Cerebellar dysfunction
Chronic cough (can be the main presenting symptom)
Autonomic dysfunction (mild and rarely disabling)
Less common neurologic findings
Cognitive impairment typically involving executive function and attention / working memory
Upper and lower motor neuron involvement: brisk reflexes, particularly in the upper limbs and at the knees. Muscle atrophy, fasciculations, and weakness are rare.
Extrapyramidal involvement: resting tremor, bradykinesia, rigidity, and postural instability.
Targeted neurological screening for RFC1-related disease in unexplained chronic cough
Findings suggest that standardized neurological and electrophysiological assessment can detect subclinical sensory neuropathy in unexplained chronic cough (UCC) patients lacking overt neurological symptoms, thereby identifying those more likely to carry RFC1 expansions. There is support for incorporating RFC1 testing into the diagnostic approach for selected UCC patients.
An Updated Canvas of the RFC1-mediated CANVAS (Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome)
How CANVAS progresses, how the illness starts, spreads, and progresses at the cellular and molecular levels, remains a subject of intensive research, yet its precise mechanisms remain elusive. This article is a comprehensive review of the epidemiology, clinical ramifications, molecular mechanisms, genetics, and potential therapeutics in light of the current findings, extending an overview of the most significant research on CANVAS.
RFC Related Disease - Molecular and Clinical Insights
Genetic studies suggest RFC1 expansions may be the most common genetic cause of ataxia and are likely underdiagnosed. This review summarizes the current molecular and clinical knowledge of RFC1-related disease, with a focus on the evaluation of recent phenotype associations and highlighting the current challenges in clinical pathways to diagnosis and molecular testing.
Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia
Using nonparametric linkage analysis and genome sequencing, we determined RFC1 (Repeat expansion in the replication Factor C subunit 1), as the cause of familial CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome) and a frequent cause of late-onset ataxia. Ataxia refers to a lack of voluntary muscle control, causing clumsy, awkward movements. It affects balance, walking, fine motor skills, speech, and eye movements.
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis
Based on a review of 27 patients with visual vestibulo-ocular reflex deficit syndrome, an impaired ability to maintain spatial orientation, it was determined that this syndrome is an integral component of CANVAS. The characteristic clinical sign - the visual vestibulo-ocular reflex deficit - can be demonstrated and measured clinically using video-oculography, a non-invasive diagnostic technique that uses infrared cameras mounted in specialized goggles to track and measure eye movements.
Rare Causes of Unexplained Chronic Cough in Adults
One of the first studies to link chronic cough to sensory neuropathies including RFC1.
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