# Doença de Charcot-Marie-Tooth autossômica dominante tipo 2

> Página oficial: https://raras.org/doenca/doenca-de-charcot-marie-tooth-autossomica-dominante-tipo-2
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 64746 — https://www.orpha.net/en/disease/detail/64746
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Uma doença de Charcot-Marie-Tooth caracterizada por alterações no axônio da célula nervosa periférica.

## Epidemiologia e herança

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

## Sinais e sintomas (262 fenótipos HPO)

- **Arreflexia** — HPO: HP:0001284
- **Amiotrofia extensora do dedo do pé** — HPO: HP:0011916
- **Atrofia do músculo fibular** — HPO: HP:0009049
- **Amiotrofia proximal** — HPO: HP:0007126
- **EMG: anormalidade axonal** — HPO: HP:0003482
- **Atrofia muscular da cintura pélvica** — HPO: HP:0008988
- **Disartria** — HPO: HP:0001260
- **Flexão limitada do joelho** — HPO: HP:0006389
- **Escápula alada** — HPO: HP:0003691
- **Hiperlordose lombar** — HPO: HP:0002938
- **Comprometimento da memória** — HPO: HP:0002354
- **Dispneia** — HPO: HP:0002094
- **Labilidade emocional** — HPO: HP:0000712
- **Comportamento atípico** — HPO: HP:0000708
- **Desequilíbrio da marcha** — HPO: HP:0002141
- **Sensação de vibração abolida** — HPO: HP:0006944
- **Fraqueza do músculo fibular** — HPO: HP:0011727
- **Formato facial anormal** — HPO: HP:0001999
- **Hipotonia generalizada** — HPO: HP:0001290
- **Discromatopsia** — HPO: HP:0007641
- **Atrofia muscular espinhal** — HPO: HP:0007269
- **Morfologia anormal da substância branca cerebral** — HPO: HP:0002500
- **Marcha em tandem prejudicada** — HPO: HP:0031629
- **Perda da deambulação** — HPO: HP:0002505
- **Insuficiência respiratória devido a fraqueza muscular** — HPO: HP:0002747
- **Anormalidade da pigmentação retiniana** — HPO: HP:0007703
- **Atrofia da medula espinhal** — HPO: HP:0006827
- **Dermatite atópica** — HPO: HP:0001047
- **Dificuldade específica de aprendizagem** — HPO: HP:0001328
- **Número diminuído de pequenas fibras nervosas mielinizadas periféricas** — HPO: HP:0007249
- **Perda axonal** — HPO: HP:0003447
- **Atrofia cerebral** — HPO: HP:0012444
- **Fadiga** — HPO: HP:0012378
- **Morfologia anormal do tórax** — HPO: HP:0000765
- **Aglomerados de regeneração axonal** — HPO: HP:0007233
- **Fraqueza muscular da cintura escapular/pélvica** — HPO: HP:0003325
- **Contratura em flexão do dedo** — HPO: HP:0012785
- **Nictalopia** — HPO: HP:0000662
- **Reflexos tendíneos reduzidos** — HPO: HP:0001315
- **Ausência de reflexos patelares** — HPO: HP:0006844
- _...e mais 222 sintomas. Ver https://raras.org/doenca/doenca-de-charcot-marie-tooth-autossomica-dominante-tipo-2._

## Genes associados (35)

- **NEFH** — Neurofilament heavy polypeptide [Disease-causing germline mutation(s) in]
  - Função: Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that
- **JPH1** — Junctophilin-1 [Candidate gene tested in]
  - Função: Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structura
- **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
- **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,
- **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
- **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
- **DGAT2** — Diacylglycerol O-acyltransferase 2 [Candidate gene tested in]
  - Função: Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage
- **NAGLU** — Alpha-N-acetylglucosaminidase [Disease-causing germline mutation(s) in]
  - Função: Involved in the degradation of heparan sulfate
- **VCP** — Transitional endoplasmic reticulum ATPase [Disease-causing germline mutation(s) 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
- **LRSAM1** — E3 ubiquitin-protein ligase LRSAM1 [Disease-causing germline mutation(s) in]
  - Função: E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral protei
- **AARS1** — Alanine--tRNA ligase, cytoplasmic [Disease-causing germline mutation(s) 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
- **GDAP1** — Ganglioside-induced differentiation-associated protein 1 [Disease-causing germline mutation(s) in]
  - Função: Regulates the mitochondrial network by promoting mitochondrial fission
- **PNKP** — Bifunctional polynucleotide phosphatase/kinase [Disease-causing germline mutation(s) in]
  - Função: Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways (PubMed:10446192, PubMed:10446193, PubMed:153859
- **TRIM2** — Tripartite motif-containing protein 2 [Disease-causing germline mutation(s) 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
- **MORC2** — ATPase MORC2 [Disease-causing germline mutation(s) 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

## Ensaios clínicos ativos (1)

- **NCT05902351** [RECRUITING]: Natural History Study for Charcot Marie Tooth Disease — https://clinicaltrials.gov/study/NCT05902351

## 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 — 105 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
- [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 — 88 sintomas em comum
- [Neuropatia motora hereditária distal autossômica dominante](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-dominante) — ORPHA:140465 — 87 sintomas em comum
- [Neuropatia motora hereditária distal autossômica recessiva](https://raras.org/doenca/neuropatia-motora-hereditaria-distal-autossomica-recessiva) — ORPHA:140468 — 79 sintomas em comum
- [Miopatia distal autossômica dominante](https://raras.org/doenca/miopatia-distal-autossomica-dominante) — ORPHA:206650 — 78 sintomas em comum
- [Atrofia muscular espinhal proximal](https://raras.org/doenca/atrofia-muscular-espinhal-proximal) — ORPHA:70 — 77 sintomas em comum
- [Paraplegia espástica complexa autossômica dominante](https://raras.org/doenca/paraplegia-espastica-complexa-autossomica-dominante) — ORPHA:100979 — 74 sintomas em comum
- [Ataxia espástica](https://raras.org/doenca/ataxia-espastica) — ORPHA:316226 — 74 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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**Citação sugerida**: Raras.org — Doença de Charcot-Marie-Tooth autossômica dominante tipo 2. Disponível em: https://raras.org/doenca/doenca-de-charcot-marie-tooth-autossomica-dominante-tipo-2
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