Fact-sheet: Hereditary hemorrhagic telangiectasia - Rendu-Osler-Weber syndrome
Updated on 02/14/2025 at 12:14 PM
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Definition
Rendu-Osler disease, or Hereditary Hemorrhagic Telangiectasia (HHT), is a vascular disease (vascular dysplasia) belonging to the phakomatoses, of autosomal dominant genetic origin with variable penetrance, characterized by the development of telangiectasias and arteriovenous malformations (AVMs) or fistulas.
Frequency of 1/8000.
Three responsible genes:
- endoglin (ENG), which encodes the TGF-beta coreceptor: predominant pulmonary involvement
- activin receptor-like kinase 1 (ACVRL1/ALK-1), which encodes one of the TGF-beta receptor dimers in endothelial cells: predominant hepatic involvement
- SMAD4, rarer (1-3%), associated with combined Rendu-Osler disease and juvenile colorectal polyposis (<4% of cases)
Clinical features
Clinical diagnosis is based on the 4 Curaçao criteria
- spontaneous or recurrent epistaxis
- cutaneous or mucosal telangiectasias (lips, tongue, fingers)
- family history: at least one first-degree relative affected, diagnosed according to these same criteria
- visceral AVMs: pulmonary, hepatic, gastrointestinal, cerebral, spinal
Definite if 3 or 4 criteria present
Possible if 2 criteria present
Unlikely if 1 criterion present
Epistaxis:
- occurring in childhood, triggered by minor factors
- recurrence and severity: iron-deficiency anemia, transfusion, impact on quality of life
Telangiectasias: cutaneous, mucosal, visceral
- round, red capillary dilations surrounded by small star-shaped vessels
Right-to-left shunt:
- dyspnea, platypnea, orthodeoxia
- hypoxia, digital clubbing
Paradoxical embolism:
- risk if feeding artery > 3 mm
- thromboembolic, gaseous (stroke, TIA), septic (abscess)
Rupture:
- favored during pregnancy due to increased cardiac output
- intrabronchial: hemoptysis
- intrapleural: hemothorax
Laboratory findings
Diagnosis confirmed by genetic testing
Ultrasound
Dilatation of the hepatic artery diameter > 6 mm
Increased systolic velocities > 80 cm/sec
Decreased resistive index < 0.55
Alteration of portal, arterial, and hepatic venous flow
Dilatation of the hepatic veins and/or main portal vein
CT
Pulmonary involvement:
20 to 50% of cases
Arteriovenous malformation (AVM) ++ and telangiectasias,
particularly in ENG and SMAD4 mutations
One or more enlarged feeding arteries supplying a serpiginous structure (fistula), from which an enlarged efferent pulmonary vein emerges.
3 types of fistulas:
- simple: 1 feeding artery
- complex segmental: 2 or more feeding arteries arising from a single hepatic segment
- complex multisegmental: 2 or more feeding arteries arising from multiple segments
Hepatic involvement:
- Abnormal intrahepatic communications or shunts between the hepatic arteries, the portal system, and the hepatic veins Arteriohepatic venous shunt: communication between hepatic artery branches and hepatic veins
- Arterioportal shunt: communication between hepatic arteries and the portal system, Portal hypertension
- Portohepatic venous shunt: communication between portal branches and hepatic veins, vascular steal of the hepatic parenchyma
- Increased caliber or flow velocities of the hepatic arteries: > 6 mm, high-flow aneurysm, atheromatous lesions
- Telangiectasias
- Tumor or pseudotumor: regenerative nodules, FNH, hemangiomas
- Perfusion abnormality: heterogeneous hepatic enhancement
- Ischemia/necrosis, hepatic abscesses, and biliary lesions
Splenic involvement
- Arterial abnormalities: increased caliber
- ectasias
- intra- or extrasplenic aneurysms
- Parenchymal abnormalities: telangiectasias
- angiomatous mass
- fistulas
Pancreatic involvement: Telangiectasias and arteriovenous fistulas
Cerebral involvement:
- Primary involvement (5-20%): AVM
- Telangiectasias
- Cavernoma
- Secondary involvement: stroke ++
- Abcess of brain
- Portosystemic shunt (manganese deposition, pallidal T1 hyperintensity)
Gastrointestinal involvement;
- 20% of patients (80-90% gastric involvement)
- Bleeding risk ++
Vascular intervention
ENT embolization: may be indicated for frequent, disabling episodes of epistaxis, using microparticles (500-700 microns), as distally as possible to preserve the pedicles supplying the nasal fossae in case repeat embolizations are needed
Embolization of pulmonary AVMs
Differential diagnosis
- Limited cutaneous systemic sclerosis
- Gastrointestinal angiodysplasia
- Isolated pulmonary, hepatic, or cerebral AVM
- Other vascular disease responsible for AVMs
- Hereditary benign telangiectasia
- Other causes of recurrent epistaxis (coagulation disorders, other nasal mucosal disease)