Hereditary hemorrhagic telangiectasia (HHT), formerly termed “Osler-Weber-Rendu syndrome,” is an autosomal dominant disorder of development of the vasculature. Epistaxis may begin in childhood or later in adolescence. Punctate telangiectases of the lips, tongue, fingers, and skin generally appear in later childhood and adolescence. Arteriovenous malformations (AVMs) can occur at any age in the brain, lungs, and liver. Bleeding from the gastrointestinal tract is due to mucosal vascular malformations (eFigures 40–7 and 40–8) and usually is not a problem until mid-adult years or later. Pulmonary AVMs can cause hypoxemia (with peripheral cyanosis, dyspnea, and clubbing) and right-to-left shunting (with embolic stroke or brain abscess). The criteria for diagnosis require presence of three of the following four features: (1) recurrent epistaxis, (2) visceral AVMs, (3) mucocutaneous telangiectases, and (4) being the near relative of a clearly affected individual. Mutation analysis can be used for presymptomatic diagnosis or exclusion of the worry of HHT.
MR or CT arteriography detects AVMs. Mutations in at least five genes can cause HHT. Three have been identified, and molecular analysis to identify them is available; these mutations in ENG, ALK1, and SMAD4 account for about 87% of families with HHT. When the familial mutation is known, molecular testing is far more cost effective than repeated clinical screening of relatives who are at risk.