JNNP: Clinical phenotype of type 2CC peroneal muscular atrophy caused by NEFH mutation

Peroneal muscular atrophy (Charcot-Marie-Tooth, CMT), also known as hereditary motor sensory neuropathy (HMSN), has obvious genetic heterogeneity.
The main clinical feature is progressive muscle weakness and atrophy of the distal limbs with sensory disturbances
.

CMT is one of the most common hereditary peripheral neuropathy (incidence rate is about 1/2500)

Peroneal muscular atrophy (Charcot-Marie-Tooth, CMT) is also known as hereditary motor sensory neuropathy (HMSN), with obvious genetic heterogeneity.

Neurofilament (of NFs) contained in a large number of neurons outside diameter of almost 10nm fiber structure
.

It is believed to have a cytoskeleton effect that maintains the morphology of neurons

Neurofilament (of NFs) contained in a large number of neurons outside diameter of almost 10nm fiber structure

The purpose of this observational cohort study was to describe the detailed phenotypes of 30 patients from 8 unrelated families and 3 carriers of asymptomatic mutations (NEFH gene mutations caused by 2CC type 2CC peroneal muscular atrophy (CMT2CC)).

The patients included in this study were recruited into the respective research protocols of the evaluation clinical center
.

The main investigator evaluated all patients with detailed phenotypic data in this study

Whole exome sequencing was performed on the five families

NEFH related to protein domains and transcription 

NEFH related to protein domains and transcription and NEFHrelated to protein domains and transcription 

In this genotype-phenotype study, phenotypic data were provided for 33 patients from 8 CMT2CC families who were caused by heterozygous pathogenic NEFH variants
.

All the variants in this study are located in the tail domain of NEFH and are encoded by exon 4

In this genotype-phenotype study, phenotypic data were provided for 33 patients from 8 CMT2CC families who were caused by heterozygous pathogenic NEFH variants

The new findings of this study and the previously published pedigree of the 2CC peroneal muscular atrophy family

This became apparent in 70% of patients (21/30) early in the course of the disease, and the average time from symptom onset to proximal involvement was 4.
4 ± 5.
4 years (SD)
.

Nine patients showed characteristics of proximal involvement, and in general, the onset of symptoms was 20 years old or later

This became apparent in 70% of patients (21/30) early in the course of the disease, and the average time from symptom onset to proximal involvement was 4.

MRI results

MRI results

Among the patients with observed symptoms, 40% showed early ankle plantar flexion weakness, which is obvious in the examination of the medical history (such as the inability to stand on the toes)
.
52% of patients (13/25) had some form of foot deformity, and patients from two of the eight families (UK1 and FR1) showed subtle upper motor neurons in the form of rapid reflexes during the examination Features
.
All patients (20/33) who underwent nerve conduction studies showed the presence of motor-based sensorimotor axon neuropathy
.
LL motor and sensory responses generally decreased or disappeared, while upper limb (UL) motor responses were only reduced in two patients over 65 years of age
.
The neurophysiological severity of neuropathy varies from patient to patient, regardless of the age of the study
.

Among the patients with observed symptoms, 40% showed early ankle plantar flexion weakness
.
LL motor and sensory responses generally decreased or disappeared, while upper limb (UL) motor responses were only reduced in two patients over 65 years of age
.
The neurophysiological severity of neuropathy varies from patient to patient, regardless of the age of the study
.

.
LL motor and sensory responses generally decreased or disappeared, while upper limb (UL) motor responses were only reduced in two patients over 65 years of age
.
The neurophysiological severity of neuropathy varies from patient to patient, regardless of the age of the study
.

In summary, this phenotype-genotype study emphasizes the unusual phenotype of CMT2CC, which is more similar to spinal muscular atrophy rather than typical CMT
.

Pipis  M ,  Cortese  A ,  Polke  JM Pipis  MPipis Cortese  ACortese Polke  JMPolke, et alCharcot-Marie-Tooth disease type 2CC due to  NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotypeNEFHJournal of Neurology , Neurosurgery & Psychiatry  Published Online First:  13 September 2021.
 Published Online First: doi:  10.
1136/jnnp-2021-327186doi:

 

 

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