Expert Reviewed By: Dr. Brandon Colby MD
Haemorrhagic telangiectasia 2 (HHT2), also known as hereditary haemorrhagic telangiectasia, is a rare genetic disorder characterized by abnormal blood vessel formation. These abnormal blood vessels can lead to various complications, such as nosebleeds, gastrointestinal bleeding, and even life-threatening conditions like ruptured arteriovenous malformations. Understanding, diagnosing, and using genetic testing for HHT2 is essential for early detection, management, and prevention of complications.
Understanding Haemorrhagic Telangiectasia 2
HHT2 is an autosomal dominant disorder, meaning that an individual only needs to inherit one copy of the mutated gene from either parent to develop the condition. The disease affects approximately 1 in 5,000 to 10,000 people worldwide. HHT2 is caused by mutations in several genes, including ENG, ACVRL1, SMAD4, and EPHB4. These genes play crucial roles in blood vessel development, and their mutations result in abnormal blood vessel formation.
EPHB4 Pathogenic Variants and HHT-like Hepatic Abnormalities
A recent study reported seven cases of EPHB4 loss-of-function variants associated with HHT-like hepatic abnormalities1. This finding suggests that EPHB4 testing may be helpful for diagnosing atypical HHT presentations. Identifying these pathogenic variants can aid in the early detection of HHT-like conditions and guide appropriate treatment strategies.
Diagnosing Haemorrhagic Telangiectasia 2
Diagnosing HHT2 can be challenging due to its variable clinical presentation. The diagnosis is typically based on a combination of clinical findings and genetic testing. The Curaçao criteria, a set of diagnostic criteria for HHT, include spontaneous and recurrent nosebleeds, multiple telangiectasias, arteriovenous malformations, and a family history of HHT. If at least three of these criteria are met, a diagnosis of HHT is considered definite.
Whole Genome Analyses to Identify Genetic Modifiers of Disease Severity
Research exploring potential phenotypic modifiers within HHT families using whole genome analysis aims to understand the varying disease severity2. Identifying genetic modifiers could help predict disease progression and severity in individuals with HHT2, allowing for better management and personalized treatment plans.
Genetic Testing for Haemorrhagic Telangiectasia 2
Genetic testing is a valuable tool for diagnosing HHT2 and identifying at-risk family members. It involves analyzing the DNA of an individual to detect mutations in the associated genes. Genetic testing can confirm a clinical diagnosis, provide information about disease severity, and guide treatment decisions.
SMAD4 Pathogenic Variants and the Full Spectrum of HHT-related Manifestations
A nationwide study investigating the phenotypic spectrum of HHT manifestations in Danish patients with SMAD4 pathogenic variants found a full spectrum of HHT-related manifestations3. This finding highlights the importance of genetic testing for SMAD4 in understanding the diverse clinical presentations of HHT2 and tailoring treatment strategies accordingly.
Importance of Early Diagnosis and Management during Pregnancy
A case report highlighted a life-threatening complication of HHT during pregnancy, emphasizing the importance of early diagnosis and management4. Genetic testing can help identify individuals with HHT2 before pregnancy, allowing for appropriate monitoring and management to prevent complications.
Conclusion
Understanding, diagnosing, and using genetic testing for haemorrhagic telangiectasia 2 is crucial in managing this rare genetic disorder. Early detection of HHT2 and its related complications can significantly improve the quality of life for affected individuals and their families. As research continues to unveil the mysteries surrounding this condition, genetic testing will play an increasingly important role in guiding personalized treatment and management strategies.
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)