Motor Neuronopathy With Widespread Fasciculations in MCM3AP‐Related Disorder: Clinical and Muscle MRI Insights

TL;DR

A patient with MCM3AP gene variants showed motor neuronopathy and unique muscle MRI findings, expanding the known effects of this genetic disorder.

Contribution

First report of MCM3AP-related motor neuronopathy with muscle MRI insights and electrophysiological evidence of denervation.

Findings

Patient with MCM3AP variants presented with motor neuronopathy and widespread fasciculations.

Muscle MRI revealed a selective pattern of fatty infiltration without length dependence.

Findings suggest overlap between hereditary motor neuropathies and anterior horn cell diseases.

Abstract

Biallelic pathogenic variants in MCM3AP, encoding the germinal center–associated nuclear protein (GANP), have been linked to autosomal recessive peripheral neuropathies variably accompanied by cognitive impairment and multisystem involvement. To date, anterior horn cell involvement has not been documented in association with MCM3AP‐related disorders.

To describe a patient with biallelic MCM3AP variants presenting with a motor neuronopathy phenotype and to provide the first whole‐body muscle MRI characterization associated with this gene.

A 53‐year‐old woman born to non‐consanguineous parents presented with early‐onset motor neuronopathy and lifelong learning difficulties. Neurological examination revealed generalized areflexia and widespread fasciculations without sensory abnormalities. Electroneuromyography demonstrated diffuse mixed acute‐on‐chronic denervation process. Whole‐body muscle MRI showed a selective non–length‐dependent pattern of fatty infiltration. Whole‐exome sequencing identified two likely pathogenic heterozygous variants in the MCM3AP gene.

According to the policies of our institution, single‐patient case reports do not require review or approval by the institutional ethics committee. Written informed consent for participation and for publication of clinical information, photographs, electrophysiological data, and muscle MRI images was obtained from the patient. No clinical trial registration was applicable.

This case extends the phenotypic spectrum of MCM3AP‐related disorders to include a slowly progressive, non‐syndromic motor neuronopathy with electrophysiological evidence of active denervation and distinctive MRI findings. These observations highlight the hidden boundaries between hereditary motor neuropathies and anterior horn cell diseases, emphasizing the need for integrated clinical, neurophysiological, and genetic evaluation.

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