Can CANVAS due to <i>RFC1</i> biallelic expansions present with pure ataxia?

Abstract

Biallelic expansion of AAGGG in the replication factor complex subunit 1 (<i>RFC1</i>) was identified as a major cause of cerebellar ataxia, neuropathy (sensory ganglionopathy, or SG) and vestibular areflexia syndrome (CANVAS). We wanted to clarify if <i>RFC1</i> expansions can present with pure ataxia and if such expansions could be responsible for some cases where an alternative diagnosis had been made. We identified patients with a combination of ataxia and SG and no other cause found, patients where an alternative diagnosis had been made, and patients with pure ataxia. Testing for <i>RFC1</i> expansions was done using established methodology. Among 54 patients with otherwise idiopathic sporadic ataxia without SG, none was found to have <i>RFC1</i> expansions. Among 38 patients with cerebellar ataxia and SG in which all other causes were excluded, 71% had <i>RFC1</i> expansions. Among 27 patients with cerebellar ataxia and SG diagnosed with coeliac disease or gluten sensitivity, 15% had <i>RFC1</i> expansions. Isolated cerebellar ataxia without SG makes the diagnosis of CANVAS due to <i>RFC1</i> expansions highly improbable, but CANVAS is frequently the cause of the combination of idiopathic cerebellar ataxia with SG. It is important to screen patients diagnosed with other causes of acquired ataxia and SG as a small percentage were found to have <i>RFC1</i> expansions.