cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome is a neurological condition that principally affects balance and coordination. It is associated with pathogenic variants in the RFC1 gene, which play a role in essential cellular processes. The condition is inherited in an autosomal recessive manner and is very rare, affecting fewer than 1 in 1,000,000 people. While the age of onset can vary, the syndrome is typically characterized by a combination of cerebellar dysfunction, sensory deficits, and vestibular impairment.

Individuals with this syndrome consistently exhibit neurological and balance-related features. Characteristic findings include gaze-evoked nystagmus, decreased distal sensory nerve action potentials, peripheral neuropathy, axonal loss, ataxia, and saccadic smooth pursuit interruptions, all reported to be present in every case. Many also experience cerebellar and limb ataxia along with additional features such as vestibular areflexia, dysmetria, intention tremor, and variable sensory deficits including impaired vibratory sensation and absent Achilles reflex. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the RFC1 gene. Although detailed molecular mechanisms are not fully explained in the available data, alterations in RFC1 are understood to disrupt normal cellular processes essential for nerve function. It is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the altered gene, one from each parent. This condition is more common when parents share a common ancestor. Because both parents must carry the same rare variant, the risk of an affected child is increased in families with shared ancestry. Genetic counseling is recommended for family planning and to discuss recurrence risk. Associated genes include RFC1.