Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia is an autosomal dominant genetic disorder that is characterized by abnormal connections between the vessels. It is a familial disorder that runs in families affecting all generations. The condition presents with abnormal vascular structures causing bleeding from the nose and gastrointestinal tract. It is characterized by telangiectatic lesions of the nose, lips, and visceral organs including the liver, spleen, gastrointestinal tract, lungs, brain, and spinal cord.

The condition occurs due to mutation occurring in various genes. The 2 important genes are responsible for the condition are located on chromosome 9 and chromosome. A deficiency of endoglin or ALK-1 causes aberrant TGF-beta signaling at some stage during vascular development leading to the formation of abnormal vessels

The condition when occurring at a young age can become life-threatening. Old people diagnosed spontaneously without any complaints don’t have severe conditions. The diagnosis is done based on the history, and physical examination and imaging tests are required for confirmation of the disease. The treatment is done based on the severity of the symptoms. The condition mainly requires surgical treatment and conservative treatment helps to reduce the symptoms, progression, and severity of the condition.

Hereditary Hemorrhagic Telangiectasia: Causes

The following are the important causes of developing Hereditary hemorrhagic telangiectasia:

• It is a genetic disorder that runs in families affecting all the generation

• The condition is transferred by autosomal dominance which affects people of all generations. If one of the parents is affected there is a 50% chance of their child getting the disease

• Several genes have been known to involve in the occurrence of the disease. The 2 important genes responsible for the condition are located on chromosome 9 (ENG, protein product: endoglin) and chromosome 12 (ACVRL1, protein product: activin receptor-like kinase 1, ALK-1); which results in HHT1 and HHT2, respectively

• The condition occurs due to a Deficiency of endoglin or ALK-1. ALK-1 is a transforming growth factor (TGF)- beta superfamily type I receptor, and endoglin associates with different signaling receptors and can modify TGF-beta-1 signaling.

• Therefore, deficiency of these causes aberrant TGF-beta signaling at some stage during vascular development resulting in the occurrence of the condition

• In type 1 HHT, pulmonary and cerebral arteriovenous malformations are more common. In type 2 HHT, hepatic arteriovenous malformations are more common.

Hereditary Hemorrhagic Telangiectasia: Symptoms

Symptoms differ from patient to patient depending on the location of the arteriovenous malformations. The patient with Hereditary hemorrhagic telangiectasia mainly presents with the following symptoms that include:

• The patients mainly present with Recurrent, spontaneous bleeding for the nose that is epistaxis

• Mucocutaneous telangiectasia is a small tiny dilated blood vessel that is visible on the skin or mucous membranes. These are most commonly found on the face, lips, tongue, fingers, and in the lining of the nose. These blood vessels are fragile and can bleed easily, leading to bleeding episodes.

• symptoms such as dark stools, and blood in the stools, are present due to bleeding in the gastrointestinal tract

• The patient appears pale and has weakness and fatigue due to chronic blood loss leading to anemia

• Difficulty in breathing and chest pain are present when the patient has pulmonary arteriovenous malformations

• Headache, seizure attacks, and paralysis can occur when the patient has cerebral arteriovenous malformations

Hereditary Hemorrhagic Telangiectasia: Risk Factors

Several factors play an important role in increasing the risk of development of hereditary hemorrhagic telangiectasia which include:

• The condition is more common in younger age groups but can occur in all age groups of people

• An individual with a family history of hereditary hemorrhagic telangiectasia. If one parent has the condition, there is a 50% chance of their child getting the disease

• The condition is more common in individuals of European descent

• Symptoms are more severe in Women who are Pregnant

• Certain environmental factors, such as smoking and exposure to toxins, can also increase the severity of the symptoms

Hereditary Hemorrhagic Telangiectasia: Diagnosis

The diagnosis of Hereditary hemorrhagic telangiectasia is mainly done based on history and some of the tests may be required for confirmation and to rule out underlying causes

• History of the symptoms such as recurrent bleeding from the nose and family history of any similar complaints should be asked for

• Physical examination should be carried out to look for the presence of telangiectasia, especially on the lips, tongue, and skin.

• The definitive clinical diagnosis of the condition is based on the presence of at least three of four main clinical features: epistaxis that is usually present since childhood; cutaneous or mucosal telangiectasias present usually on lips, tongue, oral cavity, nose, and fingers; visceral involvement such as lung, central nervous system, GI tract, or liver; and a family history of the condition

• Imaging tests, such as computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and angiography, are advised to look for the presence of abnormal blood vessels and arteriovenous malformations (AVMs) in the lungs, liver, and brain.

• Genetic testing is used to confirm a diagnosis by identifying mutations in one of the known genes associated with the condition. Also, it helps to identify family members who may be at risk for HHT.

Hereditary Hemorrhagic Telangiectasia: Treatment

The treatment is based on the severity of the symptoms. Your doctor may advise conservative or surgical treatment.

Conservative Treatment

Conservative treatment includes:

• Iron supplementation should be given to these people due to the presence of chronic bleeding in these patients

• Medications, such as estrogen-progesterone combination therapy or tranexamic acid, are given to reduce the bleeding

• Nasal embolization is done in cases if the patient has recurrent nose bleeding

• Laser therapy can be used to treat telangiectasia on the skin or mucous membranes.

Surgical Treatment

• Surgical treatment may be required in severe cases where abnormal vascular malformations are present to repair the vessels

Hereditary Hemorrhagic Telangiectasia: Prevention

There are no specific measures to prevent the occurrence of the condition as it is hereditary. Some of the measures that can help to prevent the severity of hereditary hemorrhagic telangiectasia include:

• Protection of the skin from the sun and avoid unnecessary trauma to the skin as the patients have fragile blood vessels and can cause bleeding with minor trauma

• Genetic counseling can help families with hereditary hemorrhagic telangiectasia to know the risk of their child suffering from the same disease

• Regular medical check-ups can help to diagnose the condition early and to prevent severe complications

• Avoid smoking or exposure to second-hand smoke.

• Blood thinners such as aspirin and anticoagulants, should be avoided in these patients as they increase the risk of Bleeding

Conclusion

Hereditary hemorrhagic telangiectasia is a familial autosomal dominant genetic disorder that occurs due to mutations in the various genes that are required for normal arteriovenous growth. The condition is characterized by recurrent episodes of spontaneous nose bleed, small dilated vessels present especially over the lips, tongue, oral cavity, nose, and skin, bleeding in the GI tract, and iron deficiency anemia due to chronic blood loss. The condition can affect people in any age group but is severe when presented in young individuals.

The condition is diagnosed mainly on the history of symptoms and clinical examination. Imaging tests help to identify the location of arteriovenous malformations and genetic testing help to look for the mutation of genes. Treatment can be done conservatively by nasal embolization, laser therapy, iron supplements, and pharmacological therapy to reduce the bleeding. Surgical treatment is required in severe cases to correct the arteriovenous malformations.