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J Pediatr Genet 2023; 12(04): 301-307
DOI: 10.1055/s-0042-1747934
Original Article

Clinical and Genetic Aspects of Childhood-Onset Demyelinating Charcot–Marie–Tooth's Disease in Brazil

Roberta Ismael Lacerda Machado
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
Paulo Victor Sgobbi de Souza 
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
Igor Braga Farias 
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
Bruno de Mattos Lombardi Badia
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
José Marcos Vieira de Albuquerque Filho 
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
Ricello José Vieira Lima
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
Wladimir Bocca Vieira de Rezende Pinto 
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
,
Acary Souza Bulle Oliveira
1   Department of Neurology and Neurosurgery, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
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Abstract

Charcot–Marie–Tooth's disease (CMT) represents the most common inherited neuropathy. Most patients are diagnosed during late stages of disease course during adulthood. We performed a review of clinical, neurophysiological, and genetic diagnoses of 32 patients with genetically defined childhood-onset demyelinating CMT under clinical follow-up in a Brazilian Center for Neuromuscular Diseases from January 2015 to December 2019. The current mean age was 33.1 ± 18.3 years (ranging from 7 to 71 years) and mean age at defined genetic diagnosis was 36.1 ± 18.3 years. The mean age at onset was 6.1 ± 4.4 years. The most common initial complaint was bilateral pes cavus. The genetic basis included PMP22 duplication (CMT1A) (n = 18), GJB1 (CMTX1) (n = 5), MPZ (CMT1B) (n = 3), FIG4 (CMT4J) (n = 3), SH3TC2 (CMT4C) (n = 1), PLEKHG5 (CMTRIC) (n = 1), and PRX (CMT4F) (n = 1). Almost all patients (n = 31) presented with moderate or severe compromise in the CMT neuropathy score 2 with the highest values observed in CMT1B. Medical history disclosed obstructive sleep apnea (n = 5), aseptic meningitis (n = 1/MPZ), akinetic-rigid parkinsonism (n = 1/FIG4), and overlapping chronic inflammatory demyelinating polyneuropathy (n = 1/MPZ). Motor conduction block was detected in three individuals (PMP22, FIG4, MPZ). Acute denervation occurred in seven patients. Nonuniform demyelinating patterns were seen in four individuals (two CMT1A, one CMT1B, and one CMTX1). Abnormal cerebral white matter findings were detected in CMT1A and CMTX1, while hypertrophic roots were seen in CMT1A, CMT1B, and CMTX1. Our study emphasizes a relative oligogenic basis in childhood-onset demyelinating CMT and atypical findings may be observed especially in MPZ, PMP22, and GJB1 gene variants.

Keywords

sensory or motor - neuropathy - Charcot–Marie–Tooth's disease - neuromuscular diseases - polyneuropathy

Funding

None.


Ethical Approval

This study was approved by our Institutional Ethics Board (number 0985/2019).


Authors' Contributions

R.I.L.M. conceptualized, organized, executed, analyzed and interpreted the data, contributed to writing of the first draft, conducted review and critique, helped in acquisition of data, and approved the final version to be published. P.V.S.S. conceptualized, organized, executed, analyzed and interpreted the data, contributed to writing of the first draft, and approved the final version to be published. B.M.L.B., I.B.F., and R.J.V.L. conceptualized, organized, executed the data, helped in acquisition of data, contributed to writing of the first draft, and approved the final version to be published. J.M.V.A.F. conceptualized, organized, executed the data, contributed to writing of the first draft, and approved the final version to be published. W.B.V.R.P. conceptualized, organized, executed, analyzed and interpreted the data, contributed to writing of the first draft, conducted review and critique, and approved the final version to be published. A.S.B.O. conceptualized, analyzed and interpreted the data, conducted review and critique, and approved the final version to be published.


Supplementary Material



Publication History

Received: 15 October 2021

Accepted: 07 March 2022

Article published online:
02 May 2022

© 2022. Thieme. All rights reserved.

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