Cramps as the initial presentation of CANVAS/RFC1-related disorder

Abstract

Biallelic mutations in the RFC1 gene are associated with CANVAS syndrome (cerebellar ataxia, neuropathy and vestibular areflexia). Peripheral nerve involvement in the form of sensory neuronopathy and small fiber autonomic axonopathy is a core feature of its presentation. Motor manifestations, in the other hand, remain poorly understood and incompletely characterized. We present two cases referred for evaluation of muscle cramps as the main clinical symptom, who were ultimately diagnosed with CANVAS. We also conducted a literature review on cramps and other motor manifestations as the predominant symptom in this condition. This study highlights the recognition of cramps as a possible isolated motor manifestation, expanding the phenotypic spectrum of RFC1-related disease and the need of a high index of suspicion to accurately identified the condition.