Blue Rubber Bleb Nevus Syndrome, sometimes called Bean syndrome, is a rare disorder present from birth involving the formation of abnormal blood vessels. These vascular malformations, or “blebs,” are a hallmark of the condition and can develop on the skin and within various internal organs, particularly the gastrointestinal tract.
Genetic Origins and Causes
Blue Rubber Bleb Nevus Syndrome (BRBNS) is caused by mutations in the TEK gene, also known as TIE2. This gene provides instructions for making a protein that plays a part in blood vessel formation. When the TEK gene is altered, it leads to the disorganized growth of veins that characterizes the syndrome.
These genetic mutations occur in two ways. Most are somatic, meaning the change happens in a single cell after conception and is not inherited or passed on to offspring. Less frequently, the syndrome results from a germline mutation present in the egg or sperm cells, which can be inherited from a parent.
Characteristic Signs and Complications
The most visible signs of BRBNS are distinctive lesions on the skin. These cutaneous blebs have a blue or purple color and a soft, compressible texture that has been described as rubber-like. They can range in size from millimeters to centimeters, may be found anywhere on the body, and can grow in size and number over time. These skin lesions rarely cause significant bleeding.
More concerning are the visceral lesions, or malformations, that develop inside the body, most frequently in the gastrointestinal (GI) tract. The passage of food or stool can irritate these internal blebs, causing slow, persistent bleeding. This chronic blood loss is the syndrome’s most serious complication, often leading to severe iron-deficiency anemia, a condition marked by fatigue and weakness.
While the GI tract is the most common site, these malformations can also form in other organs. The liver, lungs, central nervous system, and muscles can be affected. The location of these internal blebs determines the specific health issues an individual might face beyond anemia.
The Diagnostic Process
Diagnosis of Blue Rubber Bleb Nevus Syndrome begins with a physical examination. A doctor assesses the characteristic skin lesions and takes a detailed medical history. Because internal lesions are not visible, further tests are necessary to confirm their presence and extent.
Physicians use endoscopic procedures to locate malformations within the gastrointestinal tract. An upper endoscopy involves inserting a thin tube with a camera to examine the esophagus, stomach, and first part of the small intestine. A colonoscopy uses a similar instrument to view the large intestine. For hard-to-reach areas of the small intestine, a capsule endoscopy, where the patient swallows a small camera, may be used.
Imaging studies like Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scans detect blebs in other parts of the body, including the liver, brain, or other soft tissues. Blood tests are also a routine part of the diagnosis. A complete blood count can reveal the presence and severity of anemia by measuring red blood cell levels.
Management and Treatment Strategies
Management of BRBNS focuses on addressing anemia and treating the vascular lesions directly. Managing anemia requires consistent iron supplementation to replace iron lost through chronic bleeding. This can be administered orally or through intravenous infusions in severe cases. When bleeding is significant, blood transfusions may be necessary to restore adequate red blood cell levels.
Direct treatment of the vascular malformations aims to stop or prevent bleeding. For lesions in the GI tract accessible via endoscopy, techniques like sclerotherapy or laser photocoagulation can be used. Surgical removal (resection) of specific blebs may be performed, particularly for large ones or those causing significant symptoms.
Medical therapies offer systemic ways to manage the disorder. A class of drugs known as mTOR inhibitors, such as sirolimus, has shown effectiveness. These medications work throughout the body to interfere with cellular processes that cause abnormal blood vessel growth. This approach helps manage lesions that are widespread or difficult to treat with local procedures.