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Hereditary haemorrhagic telangiectasia

Nature Reviews Disease Primers volume 11, Article number: 1 (2025) Cite this article

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Abstract

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait and caused by loss-of-function pathogenic variants in genes encoding proteins of the BMP signalling pathway. Up to 90% of disease-causal variants are observed in ENG and ACVRL1, with SMAD4 and GDF2 less frequently responsible for HHT. In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia owing to recurrent epistaxis (nosebleeds) or bleeding from gastrointestinal telangiectases. Arteriovenous malformations (AVMs) in the lungs, liver and the central nervous system cause additional major complications and often complex symptoms, primarily due to vascular shunting, which is right-to-left through pulmonary AVMs (causing ischaemic stroke or cerebral abscess) and left-to-right through systemic AVMs (causing high cardiac output). Children usually experience isolated epistaxis; in rare cases, childhood complications occur from large AVMs in the lungs or central nervous system. Management goals encompass control of epistaxis and intestinal bleeding from telangiectases, screening for and treatment of iron deficiency (with or without anaemia) and AVMs, genetic counselling and evaluation of at-risk family members. Novel therapeutics, such as systemic antiangiogenic therapies, are actively being investigated. Although HHT is associated with increased morbidity, the appropriate screening and treatment of visceral AVMs, and the effective management of bleeding and anaemia, improves quality of life and overall survival.

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Fig. 1: Curaçao criteria and frequency of HHT features.
Fig. 2: Signalling pathways in hereditary haemorrhagic telangiectasia.
Fig. 3: Complications in hereditary haemorrhagic telangiectasia and their mechanisms.
Fig. 4: Physiopathology of pulmonary AVMs.

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Acknowledgements

The authors thank the patients for their valuable testimonials. C.L.S. acknowledges support from the National Institute for Health Research Imperial Biomedical Research Centre, London, UK.

Author information

Authors and Affiliations

  1. ENT department, Hôpital E Herriot, Hospices Civils de Lyon, Lyon, France

    Ruben Hermann

  2. European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HHT Rare Disease Working Group, Paris, France

    Ruben Hermann, Elisabetta Buscarini & Sophie Dupuis-Girod

  3. National Heart and Lung Institute, Imperial College London, London, UK

    Claire L. Shovlin

  4. Respiratory Medicine, Imperial College Healthcare NHS Trust, London, UK

    Claire L. Shovlin

  5. Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Raj S. Kasthuri

  6. Internal Medicine department, HHT Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Marcelo Serra

  7. Department of Neuroradiology, Hôpital Pierre Wertheimer, Hospices Civils de Lyon, Bron, France

    Omer F. Eker

  8. Biosanté Unit U1292, Grenoble Alpes University, INSERM, CEA, Grenoble, France

    Sabine Bailly & Sophie Dupuis-Girod

  9. Gastroenterology Department, ASST Ospedale Maggiore, Crema, Italy

    Elisabetta Buscarini

  10. HHT National Reference Center and Genetic Department, Hôpital Femme-Mère-Enfants, Hospices Civils de Lyon, Bron, France

    Sophie Dupuis-Girod

Authors
  1. Ruben Hermann
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  2. Claire L. Shovlin
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  3. Raj S. Kasthuri
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  4. Marcelo Serra
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  5. Omer F. Eker
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  7. Elisabetta Buscarini
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  8. Sophie Dupuis-Girod
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Contributions

Introduction (R.H., C.L.S. and S.D.-G.); Epidemiology (C.L.S, M.S., R.H., R.S.K. and S.D.-G.); Mechanisms/pathophysiology (S.B., C.L.S., R.H., E.B., M.S., R.S.K., O.F.E. and S.D.-G.); Diagnosis, screening and prevention (R.H., C.L.S., E.B., M.S., R.S.K., O.F.E. and S.D.-G.); Management (R.H., C.L.S., E.B., M.S., R.S.K., O.F.E. and S.D.-G.); Quality of life (R.S.K. and S.D.-G.); Outlook (R.H., C.S., E.B., M.S., R.S.K, O.F.E., S.B. and S.D.-G.); overview of the Primer (S.D.-G. and R.H.).

Corresponding author

Correspondence to Sophie Dupuis-Girod.

Ethics declarations

Competing interests

C.L.S. is listed as the inventor in the patent application filed by Imperial College London for the use of MEK1 inhibitors to treat telangiectasia in HHT (European Patent Application 23705641.1). O.F.E. is a consultant for Microvention, CERENOVUS and Balt, and is also a member of DSMB and on the advisory board for STREAM Study. All other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Disease Primers thanks C. Bernabeu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Informed consent

The authors affirm that patient participants provided informed consent for publication of their experiences.

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Supplementary information

Glossary

Cyanosis

A blue appearance of the mucous membranes caused by the presence of high quantities of deoxygenated haemoglobin in the bloodstream.

Haemoptysis

Coughing up blood from the lungs.

Haemothorax

Bleeding into the pleural cavity between the linings of the lung and chest wall.

Hypoxaemia

Low levels of oxygen in the blood.

Kiesselbach’s plexus

Also known as Little’s area, is a physiological network of small blood vessels located in the anterior part of the nasal septum.

Liver function tests

A series of blood tests used in clinical practice to determine whether the liver is likely to be healthy, or whether it shows signs of cytolysis (transaminase enzymes), biliary duct ischaemic injury (gamma glutamyl transferase, alkaline phosphatase, bilirubin) and impaired synthetic function (albumin).

proBNP test

A measure of circulating levels of a precursor of brain natriuretic peptide (BNP) that is released in high levels from a failing heart.

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Hermann, R., Shovlin, C.L., Kasthuri, R.S. et al. Hereditary haemorrhagic telangiectasia. Nat Rev Dis Primers 11, 1 (2025). https://doi.org/10.1038/s41572-024-00585-z

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