# Demência fronto-temporal

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

## Identificadores

- **ORPHA**: 282 — https://www.orpha.net/en/disease/detail/282
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A Demência Frontotemporal (DFT) abrange um grupo de doenças neurodegenerativas, ou seja, condições do cérebro que pioram com o tempo. É caracterizada por alterações progressivas no comportamento, dificuldades de planejamento e tomada de decisões (o que chamamos de disfunção executiva), e problemas de linguagem. Esses problemas surgem devido à degeneração de áreas específicas do cérebro, como as regiões pré-frontal medial e frontoinsular. Foram identificados quatro subtipos clínicos: a demência semântica, a afasia progressiva não-fluente, a DFT variante comportamental e a atrofia lobar temporal direita.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Autosomal dominant

## Sinais e sintomas (165 fenótipos HPO)

- **Paralisia bulbar** — HPO: HP:0001283
- **Morfologia anormal do neurônio motor** — HPO: HP:0002450
- **Corpos de Lewy** — HPO: HP:0100315
- **Ecolalia** — HPO: HP:0010529
- **Hiperlordose lombar** — HPO: HP:0002938
- **Agnosia visual** — HPO: HP:0030222
- **Fraqueza muscular da parede abdominal** — HPO: HP:0009023
- **Dislexia** — HPO: HP:0010522
- **Riso inapropriado** — HPO: HP:0000748
- **Fosfatase alcalina de origem óssea elevada** — HPO: HP:0010639
- **Arreflexia** — HPO: HP:0001284
- **Anormalidade da morfologia óssea da cintura pélvica** — HPO: HP:0002644
- **Disfunção do esfíncter da bexiga urinária** — HPO: HP:0002839
- **Crise tônico-clônica bilateral** — HPO: HP:0002069
- **Perda neuronal no sistema nervoso central** — HPO: HP:0002529
- **Fraqueza dos dorsiflexores do pé** — HPO: HP:0009027
- **Apraxia** — HPO: HP:0002186
- **Esclerose lateral amiotrófica** — HPO: HP:0007354
- **Emaranhados neurofibrilares** — HPO: HP:0002185
- **Comprometimento cognitivo** — HPO: HP:0100543
- **Neuropatia axonal sensorial** — HPO: HP:0003390
- **EMG: alterações neuropáticas** — HPO: HP:0003445
- **Concentração elevada de creatina quinase circulante** — HPO: HP:0003236
- **Corpos de inclusão cerebrais ubiquitina-positivos** — HPO: HP:0012083
- **Concentração reduzida de progranulina circulante** — HPO: HP:6001187
- **Escápula alada** — HPO: HP:0003691
- **Vacúolos com bordas** — HPO: HP:0003805
- **Neoplasia cerebral** — HPO: HP:0030692
- **Demência frontotemporal** — HPO: HP:0002145
- **Anormalidade da calvária** — HPO: HP:0002683
- **Afasia motora** — HPO: HP:0002427
- **Compressão de nervo craniano** — HPO: HP:0001293
- **Astrocitose** — HPO: HP:0002446
- **Ansiedade** — HPO: HP:0000739
- **Fraqueza muscular proximal** — HPO: HP:0003701
- **Distúrbio da marcha** — HPO: HP:0001288
- **Amiotrofia generalizada** — HPO: HP:0003700
- **Perda da deambulação** — HPO: HP:0002505
- **Miopatia** — HPO: HP:0003198
- **Disfunção do neurônio motor superior** — HPO: HP:0002493
- _...e mais 125 sintomas. Ver https://raras.org/doenca/demencia-fronto-temporal._

## Genes associados (11)

- **GRN** — Progranulin [Disease-causing germline mutation(s) in]
  - Função: Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:12526812, PubMed:18378771, PubMed:2807
- **MAPT** — Microtubule-associated protein tau [Disease-causing germline mutation(s) in]
  - Função: Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity (PubMed:21985311). The C-terminus binds axonal microtubules while the N-ter
- **TMEM106B** — Transmembrane protein 106B [Candidate gene tested in]
  - Função: In neurons, involved in the transport of late endosomes/lysosomes (PubMed:25066864). May be involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking (PubMed:25066864). Ma
- **PSEN1** — Presenilin-1 [Disease-causing germline mutation(s) in]
  - Função: Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precurso
- **TREM2** — Triggering receptor expressed on myeloid cells 2 [Candidate gene tested in]
  - Função: Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage produ
- **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
- **CHMP2B** — Charged multivesicular body protein 2b [Disease-causing germline mutation(s) in]
  - Função: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into
- **HNRNPA1** — Heterogeneous nuclear ribonucleoprotein A1 [Disease-causing germline mutation(s) in]
  - Função: Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection (PubMed:17371836). Plays a role in the s
- **ANXA11** — Annexin A11 [Disease-causing germline mutation(s) in]
  - Função: Binds specifically to calcyclin in a calcium-dependent manner (By similarity). Required for midbody formation and completion of the terminal phase of cytokinesis
- **SQSTM1** — Sequestosome-1 [Disease-causing germline mutation(s) in]
  - Função: Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, Pub
- **HNRNPA2B1** — Heterogeneous nuclear ribonucleoproteins A2/B1 [Disease-causing germline mutation(s) in]
  - Função: Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-

## Medicamentos em desenvolvimento (6)

- MEMANTINE HYDROCHLORIDE — Fase Phase 3 (Glutamate [NMDA] receptor negative allosteric modulator)
- MEMANTINE — Fase Phase 3 (Glutamate [NMDA] receptor negative allosteric modulator)
- TOLCAPONE — Fase Phase 2 (Catechol O-methyltransferase inhibitor)
- LITHIUM CARBONATE — Fase Phase 2 (Inositol-1(or 4)-monophosphatase 1 inhibitor)
- INSULIN HUMAN — Fase Phase 2 (Insulin receptor agonist)
- METFORMIN — Fase Phase 2 (Mitochondrial complex I (NADH dehydrogenase) inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0017276

## Ensaios clínicos ativos (16)

- **NCT03225144** [RECRUITING]: Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia — https://clinicaltrials.gov/study/NCT03225144
- **NCT07531732** [RECRUITING]: Links Between Self-awareness and Sociocognitive Processes in Neurodegenerative Diseases — https://clinicaltrials.gov/study/NCT07531732
- **NCT06064890** [RECRUITING]: A Study to Evaluate the Safety and Effect of AVB-101, a Gene Therapy Product, in Subjects With a Genetic Sub-type of Frontotemporal Dementia (FTD-GRN) — https://clinicaltrials.gov/study/NCT06064890
- **NCT03174938** [RECRUITING]: The Swedish BioFINDER 2 Study — https://clinicaltrials.gov/study/NCT03174938
- **NCT07509125** [RECRUITING]: Ultra-High Resolution PET in Aging, Neurodegeneration and Psychotic Disorders — https://clinicaltrials.gov/study/NCT07509125
- **NCT07505784** [RECRUITING]: Transcranial Alternating Current Stimulation in Frontotemporal Dementia — https://clinicaltrials.gov/study/NCT07505784
- **NCT06856850** [RECRUITING]: Disease Biosignatures in ALS/FTD Spectrum: New Impactful Biological Perspectives Beyond Clinical Approaches — https://clinicaltrials.gov/study/NCT06856850
- **NCT03489278** [RECRUITING]: Clinical Procedures to Support Research in ALS — https://clinicaltrials.gov/study/NCT03489278
- **NCT06604520** [RECRUITING]: Vortioxetine for the Treatment of Mood and Cognitive Symptoms in Frontotemporal Dementia — https://clinicaltrials.gov/study/NCT06604520
- **NCT03233646** [RECRUITING]: Retinal Imaging in Neurodegenerative Disease — https://clinicaltrials.gov/study/NCT03233646

## Doenças relacionadas (por similaridade fenotípica)

- [Miopatia com corpos de inclusão - doença de Paget - demência frontotemporal](https://raras.org/doenca/miopatia-com-corpos-de-inclusao-doenca-de-paget-demencia-frontotemporal) — ORPHA:52430 — 93 sintomas em comum
- [Miopatia de inclusão](https://raras.org/doenca/miopatia-de-inclusao) — ORPHA:206662 — 93 sintomas em comum
- [Variante comportamental da demência frontotemporal](https://raras.org/doenca/variante-comportamental-da-demencia-frontotemporal) — ORPHA:275864 — 71 sintomas em comum
- [Afasia primária progressiva](https://raras.org/doenca/afasia-primaria-progressiva) — ORPHA:95432 — 61 sintomas em comum
- [Afasia, progressiva primária, tipo não-fluente](https://raras.org/doenca/afasia-progressiva-primaria-tipo-nao-fluente) — ORPHA:100070 — 52 sintomas em comum
- [Demência frontotemporal com doença do neurônio motor](https://raras.org/doenca/demencia-frontotemporal-com-doenca-do-neuronio-motor) — ORPHA:275872 — 45 sintomas em comum
- [Miopatia distal autossômica dominante](https://raras.org/doenca/miopatia-distal-autossomica-dominante) — ORPHA:206650 — 43 sintomas em comum
- [Distrofia muscular das cinturas dos membros autossômica dominante](https://raras.org/doenca/distrofia-muscular-das-cinturas-dos-membros-autossomica-dominante) — ORPHA:102014 — 39 sintomas em comum
- [Deficiência qualitativa ou quantitativa da tropomiosina](https://raras.org/doenca/deficiencia-qualitativa-ou-quantitativa-da-tropomiosina) — ORPHA:284790 — 39 sintomas em comum
- [Miopatia nemalínica](https://raras.org/doenca/miopatia-nemalinica) — ORPHA:607 — 39 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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