Spasmodic cough preceding CANVAS phenotype in a family with biallelic repeat expansions in RFC1

Area of Science:

• Neurology
• Genetics
• Rare Diseases

Background:

• Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset, multisystem disorder.
• Previously, CANVAS was defined solely by clinical presentation.
• Recent discovery identified biallelic repeat expansion in the RFC1 gene as the genetic cause.

Purpose of the Study:

• To report the first Portuguese familial case of CANVAS.
• To characterize the clinical features and disease course of affected individuals.
• To underscore the significance of RFC1 gene mutations in late-onset ataxia.

Main Methods:

• Clinical assessment of four affected family members.
• Genetic analysis to identify RFC1 gene expansion.
• Phenotypic characterization and correlation with genetic findings.

Main Results:

• Identification of the first Portuguese familial CANVAS cohort.
• Confirmation of pathogenic RFC1 gene expansion in affected individuals.
• Detailed description of the clinical phenotype and progression in the family.

Conclusions:

• The RFC1 gene expansion is confirmed as the genetic basis for CANVAS in this Portuguese family.
• Phenotypic characterization is crucial for understanding CANVAS.
• The RFC1 mutation is likely a significant cause of idiopathic late-onset ataxia.