Background and Aims:

Axonal sensorimotor neuropathy with a chronic, indolent course is a frequent occurrence in middle-aged and older adults, often in the absence of a definite diagnosis after thorough investigations. Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) is an ataxic disorder recently associated with Replication Factor C subunit 1 (RFC1) repeat expansion mutation, presenting as a slowly evolving sensory neuro(no)pathy at onset in many cases.

We described clinical and pathological findings in RFC1-mutated patients identified in a biopsy-investigated Chronic Idiopathic Axonal Polyneuropathy (CIAP) population.

Methods:

We abstracted clinical, instrumental and pathology characteristics from 234 CIAP cases identified out of 594 consecutive patients with peripheral neuropathy evaluated at a single tertiary-care referral center for sural nerve biopsy. Patients were classified as pure sensory, predominantly sensory or sensorimotor according to clinical examination and screened for biallelic RFC1 AAGGG expansion.

Results:

A biallelic RFC1 AAGGG expansion was common in patients with pure sensory neuropathy (21/40, 53%) and more frequent compared to both predominantly sensory (10/56, 18%, P<0.001) and sensorimotor cases (3/138, 2%, P<0.001). Compared to non-mutated patients, RFC1-positive cases presented with greater sensory ataxia and autonomic disturbances, but often retained deep tendon reflexes. Cerebellar or vestibular involvement, on the other hand, was infrequent. On pathology, mutated patients showed scant regenerative changes and loss of both myelinated and unmyelinated nerve fibers, suggestive for sensory neuronopathy.

Conclusions:

RFC1 AAGGG expansion is frequently detected in patients with slowly progressive sensory axonal neuropathy of unknown cause. Specific clinical characteristics should prompt genetic testing in thoroughly investigated patients.

Background and Aims:

Axonal sensorimotor neuropathy with a chronic, indolent course is a frequent occurrence in middle-aged and older adults, often in the absence of a definite diagnosis after thorough investigations. Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS) is an ataxic disorder recently associated with Replication Factor C subunit 1 (RFC1) repeat expansion mutation, presenting as a slowly evolving sensory neuro(no)pathy at onset in many cases.

We described clinical and pathological findings in RFC1-mutated patients identified in a biopsy-investigated Chronic Idiopathic Axonal Polyneuropathy (CIAP) population.

Methods:

We abstracted clinical, instrumental and pathology characteristics from 234 CIAP cases identified out of 594 consecutive patients with peripheral neuropathy evaluated at a single tertiary-care referral center for sural nerve biopsy. Patients were classified as pure sensory, predominantly sensory or sensorimotor according to clinical examination and screened for biallelic RFC1 AAGGG expansion.

Results:

A biallelic RFC1 AAGGG expansion was common in patients with pure sensory neuropathy (21/40, 53%) and more frequent compared to both predominantly sensory (10/56, 18%, P<0.001) and sensorimotor cases (3/138, 2%, P<0.001). Compared to non-mutated patients, RFC1-positive cases presented with greater sensory ataxia and autonomic disturbances, but often retained deep tendon reflexes. Cerebellar or vestibular involvement, on the other hand, was infrequent. On pathology, mutated patients showed scant regenerative changes and loss of both myelinated and unmyelinated nerve fibers, suggestive for sensory neuronopathy.

Conclusions:

RFC1 AAGGG expansion is frequently detected in patients with slowly progressive sensory axonal neuropathy of unknown cause. Specific clinical characteristics should prompt genetic testing in thoroughly investigated patients.