Expert Reviewed By: Dr. Brandon Colby MD
Hereditary Haemorrhagic Telangiectasia 1 (HHT1) is a genetic disorder characterized by the presence of multiple abnormal blood vessels. These abnormal blood vessels can lead to bleeding, particularly in the nose and gastrointestinal tract, and may also cause arteriovenous malformations (AVMs) in various organs. In this article, we will explore the importance of understanding, diagnosing, and utilizing genetic testing for HHT1, as well as recent research findings that shed light on the disease.
Understanding Hereditary Haemorrhagic Telangiectasia 1
HHT1 is a rare disorder, affecting approximately 1 in 5,000 to 10,000 individuals worldwide. The condition is caused by mutations in the ACVRL1/ALK1 gene, which plays a crucial role in blood vessel formation and maintenance. Mutations in this gene lead to the formation of abnormal blood vessels, including telangiectases (small dilated blood vessels near the surface of the skin or mucous membranes) and AVMs (abnormal connections between arteries and veins).
Individuals with HHT1 may experience a range of symptoms, including recurrent nosebleeds, gastrointestinal bleeding, anemia, and fatigue. In some cases, AVMs can develop in the lungs, brain, or liver, leading to more severe complications such as stroke, brain abscess, or high-output heart failure.
Diagnosing Hereditary Haemorrhagic Telangiectasia 1
Diagnosing HHT1 can be challenging, as the symptoms can vary widely between individuals and may overlap with other conditions. The diagnosis is typically based on clinical findings, family history, and genetic testing. The presence of multiple telangiectases, recurrent nosebleeds, and a positive family history are strong indicators of HHT1.
Imaging studies, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), may be used to identify AVMs in the lungs, brain, or liver. In some cases, more invasive tests, such as angiography, may be necessary to confirm the presence of AVMs.
Genetic Testing for Hereditary Haemorrhagic Telangiectasia 1
Genetic testing plays a critical role in the diagnosis and management of HHT1. By identifying the specific mutation causing the disease, genetic testing can provide valuable information for both patients and healthcare providers.
Confirming the Diagnosis
Genetic testing can be used to confirm the diagnosis of HHT1 in individuals with suggestive clinical findings and a positive family history. Identification of a pathogenic ACVRL1/ALK1 mutation provides definitive confirmation of the diagnosis, allowing for appropriate medical management and surveillance for complications.
Identifying At-Risk Family Members
Because HHT1 is an inherited condition, genetic testing can also be used to identify at-risk family members who may not yet be showing symptoms. Early identification of individuals with the ACVRL1/ALK1 mutation allows for proactive management and monitoring, potentially preventing or minimizing the development of complications.
Informing Treatment and Management Strategies
Recent research has highlighted the potential for genetic testing to inform treatment and management strategies for individuals with HHT1. For example, a study found a significant excess of kinase-inactive, cell surface-expressed ACVRL1/ALK1 pathogenic missense variants in HHT1, supporting further examination of differential clinical and cellular phenotypes by HHT causal gene molecular subtypes.
Other research has investigated the neurological manifestations of HHT1 and the role of pulmonary AVMs as a risk factor for cerebral events. A study in the Danish HHT database found a high risk of ischemic stroke among HHT patients, highlighting the importance of early detection and treatment of pulmonary AVMs to reduce this risk.
Uncovering Novel Pathogenic Variants
Genetic testing has also led to the discovery of novel pathogenic variants associated with HHT1. A study in central South Africa identified three new pathogenic variants, expanding our understanding of the genetic diversity of HHT1 and potentially informing future diagnostic and therapeutic approaches.
Conclusion
As our understanding of the genetic underpinnings of Hereditary Haemorrhagic Telangiectasia 1 continues to grow, so too does the potential for improved diagnosis, treatment, and management strategies. Genetic testing plays a crucial role in this process, offering valuable insights for both patients and healthcare providers as they navigate the challenges of this rare and complex disorder.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)