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Osler-Weber-Rendu Syndrome
Wednesday, 17 November 2004
Tuesday, 30 March 2010
Hereditary Hemorrhagic Telangiectasia

What

Osler-Weber-Rendu (also known as hereditary hemorrhagic telangiectasia) is a rare disorder that affects the formation of vessels. Normally, arteries and veins connect to each other through transition vessels called capillaries. In Osler-Weber-Rendu syndrome, the arteries and veins connect directly and form abnormal structures known as arteriovenous malformations (AVMs). Small arteriovenous malformations, called telangiectasias, are usually present near the skin in mucosal membrane areas such as the nose and mouth.  Larger arteriovenous may occur in organs such as the brain, lungs, liver and digestive tract. Slight injury to areas can cause bleeding.

Who

The incidence of Osler-Weber-Rendu syndrome is variable depending on the population. In the United States, the incidence is estimated to be 1-2 per 10,000. It can affect any race or ethnic group, but is more commonly seen in Caucasians. The incidence and severity is equal in males and females.

Signs and Symptoms

Individuals with Osler-Weber-Rendu syndrome typically present with spontaneous, recurrent nosebleeds in the teenage years when entering puberty. This most common symptom affects 80-90% of those with the disorder, although the frequency and severity of the nosebleeds varies among individuals. Some people have daily nosebleeds whereas others are only affected once a month. The nosebleeds are due to bleeding of the small AVMs in the nose. The telangiectasias on the skin also appear at the same time. They look like red, raised, star-shaped lesions that blanche with pressure and are located on the nose, lips and tongue.  The number of telangiectasias generally increases with age. The large AVMs in areas such as the brain, lungs, liver and digestive tract tend to show symptoms later in life. Involvement of the brain occurs in 8-12% of individuals with Osler-Weber-Rendu and presents with headaches, seizures, weakness or numbness. About 15-33% of individuals are found with AVMs in the lungs. This can lead to difficulty with breathing, decreased ability to exercise, and even cyanosis which is a bluish-grayish discoloration of the skin due to lack of oxygen. If AVMs are located  high in the airways, coughing can cause bloody mucoid discharge. About 40% of those with Osler-Weber-Rendu develop AVMs in the liver. These AVMs in the liver don't seem to cause noticeable symptoms except for some individuals who may have right sided abdominal pain or yellow discoloration of the skin called jaundice. AVMs in the digestive tract also cause abdominal pain as well as bleeding into the stool.  Other symptoms include fatigue due to anemia which results from frequent blood loss and vision changes due to bleeding into the back of the eye.

Possible Causes

Osler-Weber-Rendu syndrome is a genetic disorder that is caused by a change or mutation in the endoglin gene (HHT-1) on chromosome 9 or the ACVRL1 (ALK gene or HHT-2) gene on chromosome 12. A third gene (HHT-3) may also cause the disease, but it has not yet been located. Continuing research is providing more information on the exact chromosomes of the above genes and their exact locations. For example, ACVRL1 as the ALK gene is thought to be located on multiple sites. All children have two copies of a given gene, one from each parent. Osler-Weber-Rendu syndrome is inherited in an autosomal dominant fashion which means that a child has to receive only one abnormal copy of the gene to be affected. A child who inherits an abnormal HHT-1 gene will have a higher incidence of AVMs in the lungs and brain while children who have an abnormal HHT-2 gene will have a higher incidence of AVMs in the liver.

Diagnosis

The diagnosis of Osler-Weber-Rendu syndrome requires the presence of at least 3 of the following: 1) spontaneous, recurrent nosebleeds, 2) multiple telangiectasias on the skin and mucus membranes, 3) AVMs in the target organs, and 4) a family history of the disease, specifically present in a first degree relative (mother, father, sister, brother). Imaging tests such as CT scan or ultrasound can be performed to look for AVMs in the organs. Colonoscopy is a test where a video camera is used to look at the insides of the large intestines and can detect and evaluate the AVMs of the digestive tract. The diagnosis can be confirmed with genetic testing for the known genetic markers.

Treatment

There is currently no cure for Osler-Weber-Rendu syndrome. The treatment is focused on reducing the number and severity of bleeding episodes. Since the blood vessels in the lungs and brain act as a filter, individuals with AVMs in those locations can experience blood clots that clog up blood flow resulting in respiratory distress, headaches or stroke. A room humidifier may be used to moisten the nasal mucous membranes thus reducing the number of nosebleeds. Also, medications with estrogen and progesterone, such as birth control pills, can help decrease bleeding from the nose and mouth. However, these medications cannot be used in patients who have AVMs in the lungs since there is an increased risk of blood clots. Procedures such as chemical cautery or electrocoagulation can be used on small lesions to destroy the abnormal blood vessels. For larger AVMs, particularly those in organs, surgery is sometimes required. Due to the frequent episodes of bleeding, many children with Osler-Weber-Rendu syndrome have anemia which can be treated with iron and folate supplementation.

Prognosis

Most children with Osler-Weber-Rendu syndrome have a normal life expectancy. The most serious complication of the disease is massive bleeding. About 10% of patients will require a blood transfusion during their lifetime for the excessive blood loss. Other serious complications are for individuals with AVMs in the lungs causing respiratory distress or those with AVMs in the brain causing migraine headaches, infections of the brain and stroke. Heart failure is another complication more commonly seen in people with AVMs in their liver.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Web links

Hereditary Hemorrhagic Telangiectasia Foundation International

http://www.hht.org/

Organization that provided information and support to individuals and families with OWR.

Telangiectasia Self Help Group

http://www.telangiectasia.co.uk/

Website that provides information on the disease and links to support sites.

References

eMedicine: http://emedicine.medscape.com/articles/957067-overview

UpToDate: Hereditary Hemorrhagic telqangiectasis (Osler-Weber-Rendu syndrome)

Zitelli B and Davis HW. Atlas of Pediatric Physical Diagnosis, fourth edition, Chapter 23 (otolaryngology) p840

Morelli J. Chapter 649 (Vascular Disorders), Part XXX (The Skin). In Nelson's Textbook of Pediatrics, 18th edition, p2673-2674

GeneReviews: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hht

Google Search for Osler-Weber-Rendu Syndrome

References and Sources

Guttmacher AE and McDonald J (2004). Hereditary Hemorrhagic Telangiectasia. www.genetests.org/profiles/hht Soriano PA, Petros J, and McKinsey JF (2003). Osler-Weber- Rendu Disease. www.emedicine.com/med/topic2764.htm