Literature
Clinical Pearls & Morning Reports
Published March 8, 2017
Clinical Pearls
Q: What are the diagnostic criteria for HHT?
A: The diagnostic criteria for HHT, which are known as the Curaçao criteria, include recurrent epistaxis, visceral arteriovenous malformations, multiple telangiectasias, and a first-degree relative with HHT.
Q: What are some of the clinical manifestations of HHT?
A: Recurrent hepatic encephalopathy can occur in patients with HHT despite the presence of normal hepatocellular function, depending on the magnitude of portosystemic shunting associated with a hepatic venovenous malformation. Pulmonary hypertension, heart failure, and anemia have all been associated with HHT. At autopsy, the hearts of patients with heart failure due to HHT are typically enlarged and have ventricular hypertrophy and dilatation. Sudden death due to HHT often results from hemorrhage into the brain, lungs, or gastrointestinal tract.
Morning Report Questions
Q: What genes have been associated with HHT or HHT-like phenotypes
A: Clinical molecular genetic testing with the use of a multigene panel formerly tested for mutations in the following three genes involved in the transforming growth factor β–bone morphogenic protein signaling pathway: ENG (also known as HHT1), which encodes the cell-surface coreceptor endoglin; ACVRL1 (previously known as ALK1 and also known as HHT2), another gene encoding a cell-surface receptor; and SMAD4, an intracellular gene that encodes a signaling molecule. Molecular genetic testing now includes tests for mutations in two additional genes (BMP9–GDF2 and RASA1) that are associated with HHT-like phenotypes.
Q: Are the different mutations associated with different phenotypes?
A: SMAD4 mutations are associated with the HHT–juvenile polyposis syndrome. As compared with ACVRL1 mutations, ENG mutations are associated with an increased occurrence of arteriovenous malformations involving the lungs or brain. As compared with ENG mutations, ACVRL1 mutations are associated with an increased occurrence of nosebleeds and of arteriovenous malformations involving the liver, as well as with pulmonary hypertension without shunting, late onset of symptoms, and arteriovenous malformations involving the spine.