Motor, Extrapyramidal, and Cognitive Involvement in RFC1 Disease

Q: What is the clinical evidence from this study?

Study design: Systematic Review. Population: RFC1 disease. Primary outcome: Prevalence and features of motor neuron, extrapyramidal, and cognitive involvement.

Sara Massucco; Mehrnaz Hamedani; Marta Ponzano; Riccardo Manca; Edoardo Roveta; Anna Pichiecchio; Carlo Asteggiano; Federico Zaottini; Maria João Malaquias; Riccardo Curró; Matteo Pardini; Angelo Schenone; Federico Massa; Andrea Cortese; Marina Grandis

doi:10.1212/nxg.0000000000200393

May 8, 2026Neurology GeneticsOpen Access

Motor, Extrapyramidal, and Cognitive Involvement in RFC1 Disease

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Key result

Systematic review evaluates the prevalence of motor neuron, extrapyramidal, and cognitive involvement in RFC1 disease.

Why the study?

Recent evidence suggests a broader phenotypic spectrum beyond cerebellar ataxia, neuropathy, and vestibular areflexia syndrome in RFC1 disease.

Key Points

To assess the prevalence and clinical features associated with motor neuron, extrapyramidal, and cognitive involvement in RFC1 disease.
Conducted a systematic review and meta-analysis of RFC1 disease literature
Evaluated clinical features and prevalence of various symptoms
Analyzed data from multiple studies on RFC1 gene mutations.
Identified significant motor, cognitive, and extrapyramidal symptoms in individuals with RFC1 gene mutations
Reported variability in symptom prevalence, indicating a broad phenotypic spectrum
Highlighted the need for awareness of cognitive involvement alongside classic motor symptoms.

Study Design

Type

Systematic Review

Structured PICO

P

Population

Patients with RFC1 disease (biallelic intronic repeat expansions in the replication factor C subunit 1 gene)

O

Outcome

Prevalence and features of motor neuron, extrapyramidal, and cognitive involvement

This systematic review and meta-analysis aims to define the broader phenotypic spectrum of RFC1 disease, specifically motor neuron, extrapyramidal, and cognitive involvement.

Implication

Supports expanded phenotyping for motor neuron, extrapyramidal, and cognitive features in RFC1 disease; extends spectrum but leaves open true prevalence and impact pending prospective studies.

Abstract

Biallelic intronic repeat expansions in the replication factor C subunit 1 (RFC1) gene are a common cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome and other late-onset ataxias. Recent evidence suggests a broader phenotypic spectrum. This systematic review and meta-analysis evaluated the prevalence and features of motor neuron, extrapyramidal, and cognitive involvement in RFC1 disease.