Management of ENG Mutation in Hereditary Hemorrhagic Telangiectasia

Genetic Testing and Diagnosis

The European Society of Cardiology recommends genetic testing for ENG mutations in patients with familial pulmonary arterial hypertension (PAH) when BMPR2 mutations are not identified, in patients with idiopathic PAH who are ≤40 years old, or when PAH occurs with personal or familial history of hereditary hemorrhagic telangiectasia 1
Genetic testing for ENG should be conducted by certified diagnostic laboratories with expertise in interpreting cardiomyopathy and vascular disorder-related mutations, as recommended by the European Heart Journal 1, 2
In patients with diffuse liver arteriovenous malformations (AVMs) who do not meet clinical diagnostic criteria for HHT, genetic testing for ENG can assist in establishing an HHT diagnosis, according to the American Association for the Study of Liver Diseases 3

Patients with confirmed ENG mutations require systematic screening for arteriovenous malformations, as these are the primary cause of morbidity and mortality in HHT, as stated by the American Heart Association 3
The American College of Radiology recommends screening for pulmonary AVMs with chest imaging, as these can cause stroke, brain abscess, or hemorrhage through paradoxical embolization 3
The American Stroke Association suggests evaluating for risk of intracerebral hemorrhage from cerebral AVMs, which is part of the clinical spectrum of HHT 3
The Society of Interventional Radiology recommends assessing hepatic vascular malformations using Doppler ultrasonography or multiphase CT, as these can cause high-output heart failure and portal hypertension 3

The European Society of Human Genetics recommends offering cascade genetic testing to all at-risk relatives to identify mutation carriers who require clinical surveillance, with first-degree relatives being tested first 1, 2
The National Comprehensive Cancer Network suggests that relatives who test negative for the family mutation can be discharged from follow-up but should be advised to seek reassessment if symptoms develop 2

The American Heart Association recommends monitoring for epistaxis, which is a hallmark clinical feature of HHT, and assessing for cutaneous or mucosal telangiectases on physical examination 3
The American Association for the Study of Liver Diseases suggests evaluating for high-output heart failure resulting from arteriohepatic and/or portohepatic shunting in patients with hepatic involvement, and monitoring for portal hypertension from arterioportal shunting or nodular regenerative hyperplasia 3

The European Society of Human Genetics recommends that trained professionals offer genetic counseling following strict local regulations regarding molecular genetic diagnosis, addressing the autosomal dominant inheritance pattern and implications for family members 1, 2
The American College of Medical Genetics and Genomics suggests discussing the strong possibility of carrying disease-causing mutations in patients with sporadic or familial PAH or pulmonary veno-occlusive disease, and ensuring patients understand the process, risks, and benefits of genetic testing without external pressures to preserve autonomy 1