# Novel genetic and nerve imaging characterization of Charcot-Marie-Tooth disease type 4F

## TL;DR

This paper describes a child with a rare nerve disorder called CMT4F and identifies a new genetic variant that may cause the disease.

## Contribution

The study identifies a novel PRX gene variant and a rare variant in the 5’ untranslated region potentially linked to CMT4F.

## Key findings

- A pathogenic PRX variant and a rare variant in the 5’ untranslated region were found in a child with CMT4F-like symptoms.
- High-resolution ultrasound showed nerve enlargement and muscle hyperechogenicity consistent with other CMT4 subtypes.
- The findings suggest these genetic variants may be causative for CMT4F.

## Abstract

Charcot-Marie-Tooth disease type 4F (CMT4F) is a rare hereditary sensorimotor neuropathy, linked to the periaxin (PRX) gene. Early onset, pronounced sensory ataxia and comparatively moderate muscular weakness are characteristic hallmarks. We here report a child with corresponding features carrying a pathogenic PRX variant in trans with a very rare variant of uncertain significance in the 5’ untranslated region predicted to interfere with splicing. High-resolution ultrasound depicted an age-related pattern of nerve enlargement and muscle hyperechogenicity resembling other CMT4 subtypes with similar clinical and histopathological characteristics. Based on this differential analysis, we propose these genetic findings to be possibly causative.

The online version contains supplementary material available at 10.1007/s10048-026-00891-6.