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CC BY 4.0 · Arq Neuropsiquiatr 2025; 83(04): s00451806820
DOI: 10.1055/s-0045-1806820
Original Article

Genetic and clinical spectrum of early growth response 2-related Charcot-Marie-Tooth disease in a Brazilian cohort

Eduardo Boiteux Uchôa Cavalcanti 
1   Rede SARAH de Hospitais de Reabilitação, Ambulatório de Reabilitação Neurológica, Brasília DF, Brazil.
,
Savana Camilla de Lima Santos 
2   Rede SARAH de Hospitais de Reabilitação, Labotatório de Patologia Molecular, Brasília DF, Brazil.
,
Christian Marques Couto 
3   Rede SARAH de Hospitais de Reabilitação, Ambulatório de Reabilitação Neurológica, Rio de Janeiro RJ, Brazil.
,
Galeno Vieira Rocha 
4   Rede SARAH de Hospitais de Reabilitação, Ambulatório de Reabilitação Neurológica, Fortaleza CE, Brazil.
,
Maria Cristina Del Negro Barroso Freitas 
1   Rede SARAH de Hospitais de Reabilitação, Ambulatório de Reabilitação Neurológica, Brasília DF, Brazil.
,
Osvaldo José Moreira do Nascimento 
5   Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Niterói RJ, Brazil.
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Abstract

Background Charcot-Marie-Tooth (CMT) disease is a genetically diverse group of hereditary neuropathies. Most studies on the frequency of CMT subtypes report that the early growth response 2 (EGR2) gene accounts for less than 1% of cases. However, data regarding the epidemiology and clinical characteristics of EGR2-related CMT in Central and South America remain limited.

Objective To characterize the clinical and genetic features of EGR2-related CMT in a Brazilian cohort.

Methods We retrospectively analyzed clinical and ancillary data from four individuals with confirmed molecular diagnosis of EGR2-related CMT. Patients were categorized based on age of onset, motor nerve conduction velocity of the ulnar nerve, and nerve biopsy findings when available. Next-generation sequencing was utilized for genetic analysis.

Results Pathogenic and likely pathogenic variants were identified exclusively in the three zinc-finger domains of EGR2, including a novel variant, c.1234G > C (p.Glu412Gln). Patients exhibited significant variation in clinical severity and phenotypes. Dysphagia, respiratory complications, and scoliosis were prominent features.

Conclusion Our findings corroborate the complex and varied clinical presentations of EGR2-related CMT, highlighting respiratory issues and dysphagia as significant features. Comprehensive clinical assessment and early genetic diagnosis are essential for managing this condition's diverse phenotypic spectrum.

Keywords

Hereditary Sensory and Motor Neuropathy - Charcot-Marie-Tooth Disease - Early Growth Response Protein 2

Authors' Contributions

EBUC: conceptualization, data curation, formal analysis, investigation, methodology, project administration, and writing – original draft; SCLS: conceptualization, data curation, investigation, and writing – review & editing; OJMN: conceptualization, formal analysis, investigation, methodology, and writing – original draft; CMC and GVR: data curation; and MCDNBF: data curation, investigation, and writing – review & editing.


Data Availability Statement

The data supporting the present study's findings are available upon reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.


Editor-in-Chief: Hélio A. G. Teive.


Associate Editor: Francisco de Assis Aquino Gondim.




Publication History

Received: 04 October 2024

Accepted: 05 January 2025

Article published online:
22 April 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Eduardo Boiteux Uchôa Cavalcanti, Savana Camilla de Lima Santos, Christian Marques Couto, Galeno Vieira Rocha, Maria Cristina Del Negro Barroso Freitas, Osvaldo José Moreira do Nascimento. Genetic and clinical spectrum of early growth response 2-related Charcot-Marie-Tooth disease in a Brazilian cohort. Arq Neuropsiquiatr 2025; 83: s00451806820.
DOI: 10.1055/s-0045-1806820
 

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