# Doença de Charcot-Marie-Tooth tipo 4

> Página oficial: https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 64749 — https://www.orpha.net/en/disease/detail/64749
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A doença de Charcot-Marie-Tooth tipo 4 (CMT4) pertence ao grupo geneticamente heterogéneo de polineuropatias sensitivo-motoras periféricas CMT.

## Epidemiologia e herança

- **Prevalência**: 1-5 / 10 000
- **Padrão de herança**: Autosomal recessive

## Sinais e sintomas (173 fenótipos HPO)

- **Atrofia do músculo esquelético** — HPO: HP:0003202
- **Fraqueza do músculo quadríceps** — HPO: HP:0003731
- **Defeito ventilatório restritivo** — HPO: HP:0002091
- **Coordenação motora grossa pobre** — HPO: HP:0007015
- **Marcha na ponta dos pés** — HPO: HP:0030051
- **Capacidade vital reduzida** — HPO: HP:0002792
- **Perda de campo visual periférico** — HPO: HP:0007994
- **Anisocoria** — HPO: HP:0009916
- **Sialorreia** — HPO: HP:0002307
- **Déficit de crescimento** — HPO: HP:0001508
- **Displasia do quadril** — HPO: HP:0001385
- **Atrofia cerebelar** — HPO: HP:0001272
- **Disartria** — HPO: HP:0001260
- **Diplopia** — HPO: HP:0000651
- **Morfologia anormal do nervo óptico** — HPO: HP:0000587
- **Mialgia** — HPO: HP:0003326
- **Fraqueza da musculatura facial** — HPO: HP:0030319
- **Reflexo aquileu diminuído** — HPO: HP:0009072
- **Neuropatia axonal crônica** — HPO: HP:0007267
- **Pé valgo** — HPO: HP:0008081
- **Fraqueza muscular da mão** — HPO: HP:0030237
- **Arreflexia dos membros superiores** — HPO: HP:0012046
- **Paralisia facial** — HPO: HP:0007209
- **Hipoventilação** — HPO: HP:0002791
- **Tremor cefálico** — HPO: HP:0002346
- **Hiporreflexia de membros superiores** — HPO: HP:0012391
- **Talipes equinovarus bilateral** — HPO: HP:0001776
- **Voz rouca** — HPO: HP:0001609
- **Pé torto** — HPO: HP:0032649
- **Fraqueza muscular proximal nos membros superiores** — HPO: HP:0008997
- **Neuropatia sensorimotora** — HPO: HP:0007141
- **Hipotonia neonatal generalizada** — HPO: HP:0008935
- **Fraqueza muscular da cintura escapular** — HPO: HP:0003547
- **Contratura articular da mão** — HPO: HP:0009473
- **Anormalidade no EMG** — HPO: HP:0003457
- **Tremor postural** — HPO: HP:0002174
- **Amiotrofia do membro inferior** — HPO: HP:0007210
- **Paralisia das cordas vocais** — HPO: HP:0001605
- **Neuralgia trigeminal** — HPO: HP:0100661
- **Sensação de dor prejudicada** — HPO: HP:0007328
- _...e mais 133 sintomas. Ver https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4._

## Genes associados (12)

- **EGR2** — E3 SUMO-protein ligase EGR2 [Disease-causing germline mutation(s) in]
  - Função: Sequence-specific DNA-binding transcription factor (PubMed:17717711). Plays a role in hindbrain segmentation by regulating the expression of a subset of homeobox containing genes and in Schwann cell m
- **HK1** — Hexokinase-1 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate
- **SH3TC2** — SH3 domain and tetratricopeptide repeat-containing protein 2 [Disease-causing germline mutation(s) in]
  - Função: Is involved in nerve myelination and is required for the integrity of nodes of Ranvier (By similarity). It probably functions as a Rab effector in the regulation of endocytic recycling (PubMed:2002879
- **SBF1** — Myotubularin-related protein 5 [Disease-causing germline mutation(s) in]
  - Função: Acts as an adapter for the phosphatase MTMR2 to regulate MTMR2 catalytic activity and subcellular location (PubMed:12668758). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab pro
- **SBF2** — Myotubularin-related protein 13 [Disease-causing germline mutation(s) in]
  - Função: Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28 (PubMed:20937701, PubMed:25648148). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins in
- **FIG4** — Polyphosphoinositide phosphatase [Disease-causing germline mutation(s) in]
  - Função: Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:17556371, Pu
- **SURF1** — Surfeit locus protein 1 [Disease-causing germline mutation(s) in]
  - Função: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly
- **MTMR2** — Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR2 [Disease-causing germline mutation(s) in]
  - Função: Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylino
- **FGD4** — FYVE, RhoGEF and PH domain-containing protein 4 [Disease-causing germline mutation(s) in]
  - Função: Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Activates MAPK8 (By s
- **PRX** — Periaxin [Disease-causing germline mutation(s) in]
  - Função: Scaffolding protein that functions as part of a dystroglycan complex in Schwann cells, and as part of EZR and AHNAK-containing complexes in eye lens fiber cells. Required for the maintenance of the pe
- **GDAP1** — Ganglioside-induced differentiation-associated protein 1 [Disease-causing germline mutation(s) in]
  - Função: Regulates the mitochondrial network by promoting mitochondrial fission
- **NDRG1** — Protein NDRG1 [Disease-causing germline mutation(s) in]
  - Função: Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase act

## Ensaios clínicos ativos (3)

- **NCT06553976** [RECRUITING]: Spastic Paraplegia - Centers of Excellence Research Network — https://clinicaltrials.gov/study/NCT06553976
- **NCT05687474** [COMPLETED]: Baby Detect : Genomic Newborn Screening — https://clinicaltrials.gov/study/NCT05687474
- **NCT01793168** [RECRUITING]: Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford — https://clinicaltrials.gov/study/NCT01793168

## Doenças relacionadas (por similaridade fenotípica)

- [Doença de Charcot-Marie-Tooth intermediária](https://raras.org/doenca/doenca-de-charcot-marie-tooth-intermediaria) — ORPHA:476123 — 89 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 1](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-1) — ORPHA:65753 — 67 sintomas em comum
- [Doença de Charcot-Marie-Tooth intermediária autossômica dominante](https://raras.org/doenca/doenca-de-charcot-marie-tooth-intermediaria-autossomica-dominante) — ORPHA:268337 — 66 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 4C](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4c) — ORPHA:99949 — 66 sintomas em comum
- [Doença de Charcot-Marie-Tooth intermediária autossômica recessiva tipo A](https://raras.org/doenca/doenca-de-charcot-marie-tooth-intermediaria-autossomica-recessiva-tipo-a) — ORPHA:217055 — 65 sintomas em comum
- [Neuropatia motora hereditária distal autossômica dominante](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-dominante) — ORPHA:140465 — 57 sintomas em comum
- [Neuropatia motora hereditária distal autossômica recessiva](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-recessiva) — ORPHA:140468 — 55 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 4B2](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4b2) — ORPHA:99956 — 54 sintomas em comum
- [Doença de Charcot-Marie-Tooth tipo 4A](https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4a) — ORPHA:99948 — 54 sintomas em comum
- [Charcot-Marie-Tooth ligada ao X](https://raras.org/doenca/charcot-marie-tooth-ligada-ao-x) — ORPHA:64747 — 52 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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**Citação sugerida**: Raras.org — Doença de Charcot-Marie-Tooth tipo 4. Disponível em: https://raras.org/doenca/doenca-de-charcot-marie-tooth-tipo-4
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