# Doença de Charcot-Marie-Tooth/neuropatia sensitiva e motora hereditária

> Página oficial: https://raras.org/doenca/doenca-de-charcot-marie-toothneuropatia-sensitiva-e-motora-hereditaria
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 166 — https://www.orpha.net/en/disease/detail/166
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Doença degenerativa hereditária que envolve os nervos periféricos. É causada por mutações nos genes responsáveis ​​pela produção de proteínas necessárias ao funcionamento e estrutura dos nervos periféricos. É caracterizada por atrofia muscular e fraqueza nos pés, pernas, mãos e braços e perda de sensibilidade nos membros.

## Epidemiologia e herança

- **Prevalência**: 1-5 / 10 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, X-linked dominant, X-linked recessive

## Sinais e sintomas (423 fenótipos HPO)

- **Desmielinização periférica** — HPO: HP:0011096
- **Amiotrofia extensora do dedo do pé** — HPO: HP:0011916
- **Atrofia muscular da cintura pélvica** — HPO: HP:0008988
- **Flexão limitada do joelho** — HPO: HP:0006389
- **Comprometimento da memória** — HPO: HP:0002354
- **Dispneia** — HPO: HP:0002094
- **Labilidade emocional** — HPO: HP:0000712
- **Comportamento atípico** — HPO: HP:0000708
- **Respostas auditivas do tronco cerebral ausentes** — HPO: HP:0004463
- **Ataxia de membro** — HPO: HP:0002070
- **Atrofia do músculo fibular** — HPO: HP:0009049
- **Sinal do canivete** — HPO: HP:0031866
- **Neuropatia óptica** — HPO: HP:0001138
- **Sensação de dor espontânea** — HPO: HP:0010833
- **Polineuropatia desmielinizante aguda** — HPO: HP:0007131
- **Formato facial anormal** — HPO: HP:0001999
- **Hipotonia generalizada** — HPO: HP:0001290
- **Discromatopsia** — HPO: HP:0007641
- **Atrofia muscular espinhal** — HPO: HP:0007269
- **Anormalidade da sensação de dor** — HPO: HP:0010832
- **Fraqueza muscular distal progressiva** — HPO: HP:0009063
- **Aumento do tecido conjuntivo endomisial** — HPO: HP:0100297
- **Sensação de vibração abolida** — HPO: HP:0006944
- **Fraqueza do músculo fibular** — HPO: HP:0011727
- **Atrofia do tibial** — HPO: HP:0011399
- **Tosse** — HPO: HP:0012735
- **Hipoplasia do músculo da panturrilha** — HPO: HP:0008962
- **Pé torto calcaneovaro** — HPO: HP:0008124
- **Anormalidade da pigmentação retiniana** — HPO: HP:0007703
- **Atrofia da medula espinhal** — HPO: HP:0006827
- **Dermatite atópica** — HPO: HP:0001047
- **Escápula alada** — HPO: HP:0003691
- **Hipoplasia do nervo óptico** — HPO: HP:0000609
- **Número diminuído de pequenas fibras nervosas mielinizadas periféricas** — HPO: HP:0007249
- **Fadiga** — HPO: HP:0012378
- **Dismielinização periférica** — HPO: HP:0003469
- **Reflexos tendinosos profundos hiperativos** — HPO: HP:0006801
- **Hiporreflexia de membros inferiores** — HPO: HP:0002600
- **Morfologia anormal do tórax** — HPO: HP:0000765
- **Fraqueza muscular da cintura escapular/pélvica** — HPO: HP:0003325
- _...e mais 383 sintomas. Ver https://raras.org/doenca/doenca-de-charcot-marie-toothneuropatia-sensitiva-e-motora-hereditaria._

## Genes associados (54)

- **PMP22** — Peroxisomal membrane protein 2 [Disease-causing germline mutation(s) in]
  - Função: Seems to be involved in pore-forming activity and may contribute to the unspecific permeability of the peroxisomal membrane
- **KARS1** — Lysine--tRNA ligase [Candidate gene tested in]
  - Função: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of th
- **VCP** — Transitional endoplasmic reticulum ATPase [Candidate gene tested in]
  - Função: Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membra
- **MME** — Neprilysin [Candidate gene tested in]
  - Função: Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:6208535, PubMed:6349683, PubMed:8168535). Biologically important in the
- **PDK3** — [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial [Candidate gene tested in]
  - Função: Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose u
- **DNAJB2** — DnaJ homolog subfamily B member 2 [Candidate gene tested in]
  - Função: Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:22219199, PubMed:7957263). In parallel,
- **TRIM2** — Tripartite motif-containing protein 2 [Candidate gene tested in]
  - Função: UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolera
- **TFG** — Protein TFG [Candidate gene tested in]
  - Função: Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (PubMed:23479643, PubMed:27813252). Required for secretory cargo traffic from the endoplas
- **PMP2** — Myelin P2 protein [Candidate gene tested in]
  - Função: May play a role in lipid transport protein in Schwann cells. May bind cholesterol
- **MORC2** — ATPase MORC2 [Candidate gene tested in]
  - Função: ATP-dependent chromatin remodeler essential for epigenetic silencing by the HUSH (human silencing hub) complex (PubMed:28581500, PubMed:29440755, PubMed:32693025). Recruited by HUSH to target site in
- **SPG11** — Spatacsin [Candidate gene tested in]
  - Função: May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport
- **DNM2** — Dynamin-2 [Candidate gene tested in]
  - Função: Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the a
- **KIF5A** — Kinesin heavy chain isoform 5A [Candidate gene tested in]
  - Função: Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE2
- **HARS1** — Histidine--tRNA ligase, cytoplasmic [Candidate gene tested in]
  - Função: Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance
- **AARS1** — Alanine--tRNA ligase, cytoplasmic [Candidate gene tested in]
  - Função: Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:27622773, PubMe

## Medicamentos em desenvolvimento (6)

- NALTREXONE HYDROCHLORIDE — Fase Phase 3 (Opioid receptors; mu/kappa/delta antagonist)
- NALTREXONE — Fase Phase 3 (Opioid receptors; mu/kappa/delta antagonist)
- BACLOFEN — Fase Phase 3 (GABA-B receptor agonist)
- ULIPRISTAL ACETATE — Fase Phase 2 (Progesterone receptor modulator)
- MEXILETINE — Fase Phase 2 (Sodium channel alpha subunit blocker)
- EPALRESTAT — Fase Phase 2 (Aldose reductase inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0015626

## Ensaios clínicos ativos (5)

- **NCT06733922** [RECRUITING]: ELIOS - Investigational Biomarkers to Track Disease Modification in Active RRMS — https://clinicaltrials.gov/study/NCT06733922
- **NCT07478172** [RECRUITING]: Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease — https://clinicaltrials.gov/study/NCT07478172
- **NCT07476365** [RECRUITING]: A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A) — https://clinicaltrials.gov/study/NCT07476365
- **NCT07090057** [RECRUITING]: The Effect of Targeting the Plantaris Muscle-tendon in Surgical Correction of Ankle Equinus in Children — https://clinicaltrials.gov/study/NCT07090057
- **NCT07424976** [ENROLLING_BY_INVITATION]: Early Detection of Brain Injury After Congenital Heart Surgery in Infants — https://clinicaltrials.gov/study/NCT07424976

## Doenças relacionadas (por similaridade fenotípica)

- [Doença de Charcot-Marie-Tooth tipo 4](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4) — ORPHA:64749 — 173 sintomas em comum
- [Doença de Charcot-Marie-Tooth intermediária](https://raras.org/doenca/doenca-de-charcot-marie-tooth-intermediaria) — ORPHA:476123 — 124 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 1](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-1) — ORPHA:65753 — 122 sintomas em comum
- [Neuropatia motora hereditária distal autossômica dominante](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-dominante) — ORPHA:140465 — 102 sintomas em comum
- [Miopatia distal autossômica dominante](https://raras.org/doenca/miopatia-distal-autossomica-dominante) — ORPHA:206650 — 102 sintomas em comum
- [Charcot-Marie-Tooth ligada ao X](https://raras.org/doenca/charcot-marie-tooth-ligada-ao-x) — ORPHA:64747 — 97 sintomas em comum
- [Atrofia muscular espinhal proximal](https://raras.org/doenca/atrofia-muscular-espinhal-proximal) — ORPHA:70 — 94 sintomas em comum
- [Doença de Charcot-Marie-Tooth autossômica dominante tipo 2Z](https://raras.org/doenca/doenca-de-charcot-marie-tooth-autossomica-dominante-tipo-2z) — ORPHA:466768 — 93 sintomas em comum
- [Neuropatia motora hereditária distal autossômica recessiva](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-recessiva) — ORPHA:140468 — 92 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 91 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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