Introduction:
Familial epistaxis syndrome, also known as hereditary hemorrhagic telangiectasia (HHT), is a genetic disorder that affects the blood vessels in the body. It is characterized by recurrent nosebleeds (epistaxis) and the development of abnormal blood vessels in the skin, mucous membranes, and organs. The condition is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutant gene from one parent to develop the disorder.
What Is an Autosomal Dominant Pattern?
Familial epistaxis syndrome is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutant gene from one parent to develop the disorder. This means that if one parent has the familial epistaxis syndrome gene mutation, there is a 50 % chance that each of their children will inherit the mutation and develop the disorder.
What Are the Causes of Familial Epistaxis Syndrome?
Mutations in genes responsible for developing abnormal blood vessels in the nose result in familial epistaxis syndrome. Several genes have been associated with familial epistaxis syndrome, the most common of which are the endoglin (ENG) gene and the ACVRL1 (ALK1) gene.
-
Mutation in Endoglin Gene - The ENG gene provides instructions for making a protein called endoglin, found on the surface of blood vessels. This protein plays a critical role in regulating the growth and formation of blood vessels. Mutations in the ENG gene lead to the production of a non-functional endoglin protein, resulting in abnormal blood vessel development and recurrent nosebleeds.
-
Mutation in ALK1 Gene - The ALK1 gene provides instructions for making a protein called activin receptor-like kinase 1, also found on the surface of blood vessels. Like endoglin, this protein plays a critical role in regulating the growth and formation of blood vessels. Mutations in the ALK1 gene produce a non-functional activin receptor-like kinase one protein, leading to abnormal blood vessel development and recurrent nosebleeds.
What Are the Symptoms of Familial Epistaxis Syndrome?
It is characterized by recurrent nosebleeds (epistaxis) and the development of abnormal blood vessels in the skin, mucous membranes, and organs. Some individuals may experience various symptoms, while others may only experience one or two. It is essential to know that the symptoms described below are typical, but they can vary significantly in severity and frequency among affected individuals. Also, not everyone with hereditary hemorrhagic telangiectasia (HHT) will have all symptoms. The symptoms of HHT can vary widely among affected individuals, even among family members with the same mutation. Symptoms include the following -
Recurrent Nosebleeds (Epistaxis) -
-
The most common symptom of HHT is recurrent nosebleeds, ranging from mild to severe.
-
Some individuals experience nosebleeds only occasionally, while others experience them daily.
-
Nosebleeds may be spontaneous or triggered by minor injuries, such as nose-picking or blowing.
-
In some cases, the nosebleeds can be so severe that they require hospitalization.
Development of Abnormal Blood Vessels (Telangiectasia) -
-
Another symptom of HHT is the development of abnormal blood vessels in the skin, known as telangiectases.
-
These are small, red, or purple spots, usually less than 1 centimeter in diameter.
-
Telangiectases can occur anywhere on the body but are most commonly found on the face, hands, and lips.
-
They may be visible to the naked eye or may require an examination with a particular instrument called a Woods lamp to be seen.
Complications of Other Internal Organs -
-
Internal organs can also be affected by HHT. Abnormal blood vessels can develop in the lungs, liver, and brain.
-
This can lead to severe complications such as lung and brain bleeding and high blood pressure in the liver.
-
These symptoms may only appear in adulthood, and thus HHT is often undiagnosed.
-
Symptoms of HHT on internal organs may include shortness of breath, chest pain, fatigue, and easy bruising.
-
Brain abnormalities may result in cognitive decline, balance and coordination issues, seizures, and headaches.
-
In some cases, HHT can also affect other organs, such as the gastrointestinal tract and the skeletal system.
How to Diagnose Familial Epistaxis Syndrome?
Diagnosis of familial epistaxis syndrome is based on clinical criteria. The most widely used set of criteria is called the Curaçao criteria, which includes the presence of recurrent nosebleeds, multiple telangiectasias, and a family history of familial epistaxis syndrome. To be diagnosed with familial epistaxis syndrome, a person must have at least two of the following three criteria -
-
Recurrent nosebleeds (epistaxis).
-
Multiple telangiectasias (abnormal blood vessels on the skin, mucous membranes, or organs).
-
A family history of familial epistaxis syndrome.
What Are the Diagnostic Methods of Familial Epistaxis Syndrome?
Diagnosis involves the following steps -
1. Patient History and Examination - When a patient presents with recurrent nosebleeds and telangiectases, a medical professional will typically begin by taking a detailed patient history, including information on family history, symptoms, and medical history. A physical examination will identify telangiectases and look for other physical signs of familial epistaxis syndrome.
2. Imaging Tests - CT (computed tomography) scans or MRIs (magnetic resonance imaging) are done to detect abnormal blood vessels in internal organs, particularly the lungs, liver, and brain. These tests can help to identify the presence of abnormal blood vessels and to evaluate the severity of the condition.
3. Genetic Testing - In addition to the clinical criteria, genetic testing can be used to confirm a diagnosis of familial epistaxis syndrome. Genetic testing can detect specific mutations in the genes associated with Familial epistaxis syndrome and can also be used to determine if a person is at risk of inheriting the condition from a parent. However, genetic testing is not always necessary for diagnosis, especially if the clinical criteria are met.
What Is the Treatment of Familial Epistaxis Syndrome?
Treatment for familial epistaxis syndrome focuses on controlling symptoms and preventing complications. A multidisciplinary team approach is recommended to manage all the different organs affected by the disorder.
1. Treatment of Recurrent Nosebleeds (Epistaxis) -
-
Cauterization - A procedure that uses heat or a chemical substance to stop bleeding. It is a quick and effective treatment for nosebleeds and can be performed by a specialist in an outpatient setting.
-
Topical Estrogen Therapy - Estrogen medication is applied to the inside of the nose to help control nosebleeds.
-
Embolization - In severe cases, embolization is a procedure that blocks blood flow to the abnormal vessels. An interventional radiologist typically injects a substance into the blood vessels to block blood flow to the vessels, causing nosebleeds.
2. Treatment of Lung Complications - Regular monitoring by a pulmonologist is crucial to detect any lung changes early, such as lung bleeding. Treatments include embolization, surgery, and medications to reduce bleeding.
3. Treatment of Liver Complications - Regular monitoring by a gastroenterologist and hematologist is essential for early detection of any change in the liver, such as high blood pressure in the liver (portal hypertension). Treatments include medications, and liver transplantation may be considered in severe cases.
4. Treatment of Brain Complications - Regular monitoring by a neurologist and neuro-radiologist is essential for early detection of any changes in the brain, such as brain bleeding (brain’s arteriovenous malformations) and malformations. Treatments include embolization, surgery, and medications to reduce bleeding.
Conclusion:
Treatment for familial epistaxis syndrome focuses on controlling symptoms and preventing complications. In severe cases, treatment options for recurrent nosebleeds include cauterization, topical estrogen therapy, and embolization. To prevent complications, it is essential to undergo regular monitoring by a multidisciplinary team, including an internist, a hematologist, and a pulmonologist, to detect any changes in the lungs and liver early. Currently, there is no cure for familial epistaxis syndrome, but the quality of life for affected individuals can be improved with treatment and management. Patients need to work closely with their healthcare providers.
