# Hereditary, non HINT1 related, axonal neuropathy with neuromyotonia

## TL;DR

Two unrelated men with a rare inherited nerve disorder were found to have a mutation in the MPZ gene, suggesting a new type of hereditary neuropathy with neuromyotonia.

## Contribution

Identifies a novel autosomal dominant MPZ mutation causing axonal neuropathy with neuromyotonia, expanding the CMT disease spectrum.

## Key findings

- Two unrelated patients with late-onset axonal neuropathy and neuromyotonia shared an autosomal dominant MPZ mutation.
- Clinical features included progressive muscle weakness, stiffness, and electrophysiological signs of length-dependent neuropathy.
- This mutation defines a new subtype of Charcot-Marie-Tooth disease with neuromyotonia.

## Abstract

To date, neuromyotonia in the context of an inherited axonal neuropathy has been linked to autosomal recessive mutations in the histidine triad nucleotide binding protein 1 (HINT1) gene. In this study we describe two unrelated male patients with late-onset, predominantly motor, axonal neuropathy with neuromyotonia, who carried an autosomal dominant c.103G > A mutation in the myelin protein zero (MPZ) gene (NM_000530.8:c.103G > A, p.Asp35Asn), identified by whole-exome sequence analysis (WES).

The first patient presented progressive leg muscle weakness and stiffness with difficulty in walking, pain and increased creatine kinase levels,during his fifth decade of life. Electrophysiological examination revealed findings of an axonal, length-dependent polyneuropathy with spontaneous activity, mainly neuromyotonia. Over the 20-year disease course since the first reported symptoms, muscle weakness gradually worsened and he is currently unable to walk without assistance. A second male patient, unrelated to the first one, showed similar clinical and electrophysiological features of a length-dependent axonal neuropathy with neuromyotonia. WES detected the same MPZ missensevariant.

This study suggests a novel entity in the spectrum of Charcot-Marie-Tooth hereditary neuropathies, characterized by autosomal dominant axonal neuropathy with neuromyotonia (AD-NMAN).

The online version contains supplementary material available at 10.1007/s10072-025-08022-z.