# Hipertensão arterial pulmonar hereditária

> Página oficial: https://raras.org/doenca/hipertensao-arterial-pulmonar-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**: 275777 — https://www.orpha.net/en/disease/detail/275777
- **CID-10**: I27.0
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A Hipertensão Arterial Pulmonar Hereditária (HPAH) é um tipo de Hipertensão Arterial Pulmonar (HAP) que acontece por causa de alterações (mutações) em genes que predispõem à HAP, ou quando há casos na família. A HPAH se caracteriza por uma resistência alta nas artérias dos pulmões, o que leva à falha do lado direito do coração. É uma doença progressiva e que pode ser fatal.

## Epidemiologia e herança

- **Prevalência**: <1 / 1 000 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive

## Sinais e sintomas (39 fenótipos HPO)

- **Hipertrofia ventricular direita** — HPO: HP:0001667
- **Dispneia de esforço** — HPO: HP:0002875
- **Fibrose intimal arterial pulmonar** — HPO: HP:0005312
- **Pressão elevada do átrio direito** — HPO: HP:0005168
- **Dispneia** — HPO: HP:0002094
- **Insuficiência ventricular direita** — HPO: HP:0001708
- **Trombose anormal** — HPO: HP:0001977
- **Vasoconstrição da artéria pulmonar** — HPO: HP:0005308
- **Aumento da resistência vascular pulmonar** — HPO: HP:0005317
- **Hipertrofia medial arterial pulmonar** — HPO: HP:0004964
- **Hipertensão arterial pulmonar** — HPO: HP:0002092
- **Fraqueza muscular** — HPO: HP:0001324
- **Síncope** — HPO: HP:0001279
- **Pressão elevada da artéria pulmonar** — HPO: HP:0004890
- **Componente pulmonar anormalmente alto da segunda bulha cardíaca** — HPO: HP:0031687
- **Fadiga fácil** — HPO: HP:0003388
- **Fadiga** — HPO: HP:0012378
- **Hipertensão arterial pulmonar com falta de resposta aguda ao teste de NO** — HPO: HP:0033424
- **Espessamento do septo alveolar** — HPO: HP:0033376
- **Opacificação em vidro fosco na TC de alta resolução pulmonar** — HPO: HP:0025179
- **Déficit de crescimento** — HPO: HP:0001508
- **Insuficiência respiratória** — HPO: HP:0002093
- **Apneia** — HPO: HP:0002104
- **Tromboembolismo** — HPO: HP:0001907
- **Bloqueio do ramo direito** — HPO: HP:0011712
- **Flutter atrial** — HPO: HP:0004749
- **Bloqueio atrioventricular de primeiro grau** — HPO: HP:0011705
- **Aumento da concentração circulante de NT-proBNP** — HPO: HP:0031185
- **Macrófagos carregados de hemossiderina no líquido broncoalveolar** — HPO: HP:0032979
- **Nascimento prematuro** — HPO: HP:0001622
- **Hemangiomatose capilar pulmonar** — HPO: HP:0005954
- **Bloqueio atrioventricular** — HPO: HP:0001678
- **Cianose** — HPO: HP:0000961
- **Cardiomiopatia hipertrófica** — HPO: HP:0001639
- **Tosse** — HPO: HP:0012735
- **Fibrose intimal arterial** — HPO: HP:0011353
- **Hipertensão** — HPO: HP:0000822
- **Telangiectasia** — HPO: HP:0001009
- **Angina pectoris** — HPO: HP:0001681

## Genes associados (12)

- **CAPNS1** — Calpain small subunit 1 [Disease-causing germline mutation(s) in]
  - Função: Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Essential for em
- **BMPR2** — Bone morphogenetic protein receptor type-2 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autopho
- **ATP13A3** — Polyamine-transporting ATPase 13A3 [Disease-causing germline mutation(s) in]
  - Função: ATP-driven pump involved in endocytosis-dependent polyamine transport. Uses ATP as an energy source to transfer polyamine precursor putrescine from the endosomal compartment to the cytosol
- **GDF2** — Growth/differentiation factor 2 [Disease-causing germline mutation(s) in]
  - Função: Potent circulating inhibitor of angiogenesis. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/
- **KCNK3** — Potassium channel subfamily K member 3 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where ou
- **SOX17** — Transcription factor SOX-17 [Major susceptibility factor in]
  - Função: Acts as a transcription regulator that binds target promoter DNA (PubMed:33952808). Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits Wnt s
- **CAV1** — Caveolin-1 [Disease-causing germline mutation(s) in]
  - Função: May act as a scaffolding protein within caveolar membranes (PubMed:11751885). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the
- **EIF2AK4** — eIF-2-alpha kinase GCN2 [Disease-causing germline mutation(s) (loss of function) in]
  - Função: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:2532
- **SMAD9** — SMAD family member 9 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor-regulated SMAD (R-SMAD)
- **TBX4** — T-box transcription factor TBX4 [Disease-causing germline mutation(s) in]
  - Função: Transcriptional regulator that has an essential role in the organogenesis of lungs, pelvis, and hindlimbs
- **ENG** — Endoglin [Candidate gene tested in]
  - Função: Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (P
- **ACVRL1** — Activin receptor type-1-like [Candidate gene tested in]
  - Função: Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and tw

## Ensaios clínicos ativos (29)

- **NCT07318597** [RECRUITING]: Phase 2 Study of REGN13335 in Adult Participants With Pulmonary Arterial Hypertension (PAH) — https://clinicaltrials.gov/study/NCT07318597
- **NCT07218029** [RECRUITING]: A Clinical Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (MK-7962-038) — https://clinicaltrials.gov/study/NCT07218029
- **NCT05967299** [RECRUITING]: Study of Intravenous ZMA001 in Healthy Subjects — https://clinicaltrials.gov/study/NCT05967299
- **NCT05587712** [RECRUITING]: Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008) — https://clinicaltrials.gov/study/NCT05587712
- **NCT01712620** [RECRUITING]: Spironolactone for Pulmonary Arterial Hypertension — https://clinicaltrials.gov/study/NCT01712620
- **NCT07175038** [RECRUITING]: A Study of ROC-101 in Patients With Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated With Interstitial Lung Disease (ILD-PH) (ROCSTAR STUDY) — https://clinicaltrials.gov/study/NCT07175038
- **NCT04278404** [RECRUITING]: Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) — https://clinicaltrials.gov/study/NCT04278404
- **NCT03838445** [RECRUITING]: Reducing Right Ventricular Failure in Pulmonary Arterial Hypertension (RELIEVE-PAH) — https://clinicaltrials.gov/study/NCT03838445
- **NCT06549452** [RECRUITING]: Mobile Health Intervention to Improve Exercise in Pediatric PH — https://clinicaltrials.gov/study/NCT06549452
- **NCT06554301** [RECRUITING]: A Study on the Efficacy and Safety of Empagliflozin in the Treatment of Pulmonary Arterial Hypertension — https://clinicaltrials.gov/study/NCT06554301

## Doenças relacionadas (por similaridade fenotípica)

- [Hipertensão arterial pulmonar idiopática/hereditária](https://raras.org/doenca/hipertensao-arterial-pulmonar-idiopaticahereditaria) — ORPHA:422 — 39 sintomas em comum
- [Hipertensão arterial pulmonar](https://raras.org/doenca/hipertensao-arterial-pulmonar) — ORPHA:182090 — 39 sintomas em comum
- [Comunicação interatrial](https://raras.org/doenca/comunicacao-interatrial) — ORPHA:1478 — 15 sintomas em comum
- [Defeito do septo atrial, tipo ostium primum](https://raras.org/doenca/defeito-do-septo-atrial-tipo-ostium-primum) — ORPHA:99106 — 13 sintomas em comum
- [Anomalia dos grandes vasos (aorta, arco aórtico, artérias pulmonares), congênita](https://raras.org/doenca/anomalia-dos-grandes-vasos-aorta-arco-aortico-arterias-pulmonares-congenita) — ORPHA:98724 — 12 sintomas em comum
- [Policitemia](https://raras.org/doenca/policitemia) — ORPHA:98427 — 11 sintomas em comum
- [Defeito do canal auriculoventricular](https://raras.org/doenca/defeito-do-canal-auriculoventricular) — ORPHA:98722 — 11 sintomas em comum
- [Proteinose congênita dos alvéolos pulmonares](https://raras.org/doenca/proteinose-congenita-dos-alveolos-pulmonares) — ORPHA:264675 — 10 sintomas em comum
- [Doença venoclusiva pulmonar](https://raras.org/doenca/31837) — ORPHA:31837 — 10 sintomas em comum
- [Doença mieloproliferativa crônica](https://raras.org/doenca/doenca-mieloproliferativa-cronica) — ORPHA:98274 — 10 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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