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Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia type 1)

Epidemiology: 1) inherited disorder 2) female:male ratio is 2:1 Pathology: 1) pulmonary arteriovenous (AV) malformations/fistulas (20%) a) located in lower lobes b) multiple in 1/3 of patients c) diagnosed in 3rd or 4th decade of life d) an artery enters malformation/fistula, a vein leaves it e) pulmonary hypertension & heart failure may occur [6] 2) AV malformations in the liver & mucous membranes 3) central nervous system angiomas, AV malformations of the brain Genetics: 1) autosomal dominant 2) may be caused by mutations in the genes for endoglin, SMAD4 & activin receptor-like kinase 1 [9] Clinical manifestations: 1) telangiectasias a) skin - extremities a) mucosal surfaces - lip & perioral region - buccal mucosa c) brain, liver, lung d) similar lesions in the GI tract 2) hemorrhage a) upper GI bleed b) hemoptysis is most common presenting symptom c) epistaxis 3) dyspnea in 60% of patients 4) cyanosis 5) clubbing of nails 6) a bruit or continuous murmur or site of AV malformation 7) symptoms depend on degree of right to left shunt 8) headaches or vertigo resulting from AV malformations of the brain Diagnostic criteria: - recurrent epistaxis - visceral arteriovenous malformations - multiple telangiectasias - first-degree relative with Osler-Weber-Rendu syndrome [6] * even without a confirmed family history, 3 of criteria make diagnosis Laboratory: 1) complete blood count may show anemia, may be iron-deficiency anema 2) ENG gene mutation 3) see ARUP consult [5] Special laboratory: - cardiac catheterization a) decreased PaO2 b) decreased SaO2 c) normal pulmonary artery pressure d) pulmonary hypertension has been noted in some patients [6] - pulmonary angiography confirms diagnosis Radiology: 1) chest X-ray - AV malformations appear as oval or round homogeneous lesions, a few mm to several cm in size 2) computed tomography of thorax - shows an artery enters malformation/fistula, a vein leaves it 3) pulmonary angiography confirms diagnosis 4) CT of brain to evaluate for AV malformations Complications: - paradoxic embolism resulting in CNS symptoms - hepatic venovenous malformation with portosystemic shunting may result in hepatic encephalopathy [6] - seizures resulting from AV malformations of the brain Differential diagnosis: - von Willebrand's disease - not associated with arteriovenous malformations or headaches Management: 1) therapeutic catheter-directed embolization of AV malformation 2) surgical resection of AV malformation

Related

Osler-Weber-Rendu syndrome 2; hereditary hemorrhagic telangiectasia type 2 (HHT2, ORW2)

Specific

juvenile polyposis with hereditary hemorrhagic telangiectasia (JPHT)

General

genetic disease of the skin (genodermatosis) genetic syndrome (multisystem disorder)

Database Correlations

OMIM 187300

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 300
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 173, 757
  3. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 525
  4. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1039
  5. ARUP Consult: Hereditary Hemorrhagic Telangiectasia - HHT The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hereditary-hemorrhagic-telangiectasia
  6. Fogerty RL, Greenwald JL, McDermot S Case 7-2017 - A 73-Year-Old Man with Confusion and Recurrent Epistaxis. N Engl J Med 2017; 376:972-980. March 9, 2017 PMID: 28273029 http://www.nejm.org/doi/full/10.1056/NEJMcpc1613462
  7. Faughnan ME, Mager JJ, Hetts SW et al Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020 Dec 15;173(12):989-1001 PMID: 32894695 Free article
  8. McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med. 2011 Jul;13(7):607-16. PMID: 21546842 Free article. Review.
  9. NEJM Knowledge+ Hematology