Osler-Weber-Rendu syndrome Health Article

Definition

Osler-Weber-Rendu syndrome (OWR), or hereditary hemorrhagic telangiectasia (HHT), is a blood vessel disorder, typically involving recurrent nosebleeds and telangiectases (arteriovenous malformations that result in small red spots on the skin) of the lips, mouth, fingers, and nose. Arteriovenous malformations (AVMs) are abnormal, direct connections between the arteries and veins (blood vessels), causing improper blood flow. AVMs are often present in OWR, and may occur in the lungs, stomach, or brain.

Description

The story of OWR began years ago with a sequence of events between three prominent physicians, Osler, Weber, and Rendu. The earliest report of OWR was compiled by Rendu in 1896. Osler further characterized the condition in 1901, and F. Parkes Weber described many cases of the vascular problems as well. OWR is caused by a genetic defect in the development of blood capillaries. Capillaries are vessels that exist between arteries and veins, connecting them throughout the body. The abnormality causes the capillaries to end bluntly, so they cannot properly connect the arteries and veins. Because of this, AVMs and telangiectases may result in various parts of the body.

Telangiectases on the skin represent a small AVM that has reached the outer surface of skin. Telangiectases usually have thin walls and are quite fragile, so they may burst spontaneously, causing bleeding. This bleeding may occur in the nose, explaining the frequent nosebleeds that result from little trauma. Telangiectases most often occur on the cheeks, lips, tongue, fingers, mouth, and toes. Occasionally, larger AVMs may exist in the brain, lungs, or stomach and this may lead to more serious bleeding. It is very rare for an individual to have all the symptoms typically found in OWR.

People with OWR do not have any mental limitations, and therefore have the same academic potential as anyone else. Nosebleeds may begin by age twelve, and may be initially assumed to be a typical childhood experience. However, if fatigue and other symptoms of anemia accompany the nosebleeds, they can pose great stress on a young child. Children with OWR may find it difficult if they play with and are unable to keep up with their peers. OWR has the potential need for continual medical management into adulthood, which can also be quite taxing on the individual and his or her family.

Genetic profile

OWR may be divided into two groups, OWR1 and OWR2. OWR1 is caused by alterations in the endoglin (ENG) gene, located on the q (long) arm of chromosome 9 at band (location) 34. AVMs of the lung may be more common in OWR1 than OWR2. OWR2 is caused by alterations in the activin receptor-like kinase 1 gene (ALK1), located on the q arm of chromosome 12 at band 1. Normally, ENG and ALK1 make proteins that are important in blood vessel formation. Therefore, alterations within these genes would naturally cause problems with blood vessels. The causes of OWR are complex; various alterations in multiple genes, or various alterations within the same gene, generate similar symptoms.

OWR is inherited in an autosomal dominant manner. An affected individual has one copy of an alteration that causes OWR. The individual has a 50% chance to pass the alteration on to each of his or her children, regardless of that child's gender. As of 2000, nearly all affected people have a family history of OWR, which is typically a parent with the condition.

Demographics

As of 2000, OWR affects about one in 10,000 people. It spans the globe, but a higher prevalence exists in the Danish island of Fyn, the Dutch Antilles, and parts of France. It affects both males and females.

Signs and symptoms

The symptoms in OWR result from several AVMs, which may occur in differing severity and areas of the body. Ultimately, AVMs may lead to mild or severe bleeding in affected areas. As of 1998, about 90% of people with OWR experience frequent nosebleeds. They occur because the layers of mucous membranes in the nose are very sensitive and fragile, and AVMs in this area can easily and spontaneously bleed. Consistent nosebleeds may begin by about twelve years of age, and are not always severe enough to result in medical treatment or consultation. Occasionally, severe nosebleeds can cause mild to severe anemia, sometimes requiring a blood transfusion or iron replacement therapy.

Small AVMs, called telangiectases, commonly occur on the nose, lips, tongue, mouth, and fingers. They may vary in size from a pinpoint to a small pea. Because telangiectases are fragile, sudden bleeding may occur from only slight trauma, and bleeding may not spontaneously stop. Thirty percent of people with OWR report telangiectases first appearing before age 20, and 67% before age 40. Telangiectases and larger AVMs can be found anywhere in the gastrointestinal system, and if large enough they may cause a significant amount of internal bleeding. This bleeding may become more severe with age, but usually does not appear until age forty.

Pulmonary AVMs (AVMs of the lung) may cause bleeding within the lungs. As of 1998, this occurs in about 20% of people with OWR. These are problematic because the abnormal connections between arteries and veins bypass the natural filtering system within the lung, allowing bacteria to enter the system. Low levels of oxygen and infection may result, causing migraine-like headaches. An individual with a pulmonary AVM may experience intolerance to exercise, or may have areas of their skin turn blue (due to low oxygen levels). Complications in the brain may also result, sometimes causing a stroke. Occasionally, AVMs may occur in the spine, liver, and brain. A network of AVMs in the liver can cause blood to be forced away from the normal circulation, increasing the risk of heart failure because the heart becomes overloaded with blood.