RT Book, Section A1 Pyeritz, Reed E. A2 Murray, Michael F. A2 Babyatsky, Mark W. A2 Giovanni, Monica A. A2 Alkuraya, Fowzan S. A2 Stewart, Douglas R. SR Print(0) ID 1102706719 T1 Hereditary Hemorrhagic Telangiectasia T2 Clinical Genomics: Practical Applications in Adult Patient Care YR 2014 FD 2014 PB McGraw-Hill Education PP New York, NY SN 9780071622448 LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102706719 RD 2024/03/29 AB Disease summary:Hereditary hemorrhagic telangiectasia (HHT) is a disorder of vascular development that results in direct communication between arteries and veins.Multiple organs are affected and the development of clinical features is age dependent. Telangiectases in the nose cause epistaxis severe enough to cause chronic anemia. Vascular anomalies in the brain and spinal column cause stroke or seizures. Pulmonary arteriovenous malformations (PAVMs) cause hypoxemia and high-output cardiac failure because of shunting and provide a conduit for clots and bacteria to cause embolic stroke and cerebral abscess. Hepatic AVMs cause high-output cardiac failure and cirrhosis. A late finding is gastrointestinal (GI) telangiectases that cause chronic blood loss.While today mortality is only modestly increased, the clinical features cause considerable morbidity and diminished quality of life.Hereditary basis:HHT is an autosomal dominant condition of considerable variability found in all populations. Reproduction is little affected so sporadic cases are uncommon. Most cases (>80%) are due to mutations in either ENG or ACVRL1, the products of which function as cell surface receptors in the TGF-β/BMP signaling pathway. Mutations in SMAD4 cause HHT combined with juvenile polyposis. Some families show linkage to none of these loci.Differential diagnosis:A number of syndromes include cutaneous or sclera telangiectases (ataxia telangiectasia, CREST syndrome, chronic liver disease, hereditary benign telangiectasia, pregnancy) but not the visceral vascular anomalies.An isolated PAVM can occur in the absence of other features of HHT.Vascular dysplasias can accumulate in GI mucosa with age and cause chronic blood loss.