Klippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues, and bones. The disorder has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations.
Most people with Klippel-Trenaunay syndrome are born with a port-wine stain. This type of birthmark is caused by swelling of small blood vessels near the surface of the skin.
Port-wine stains are typically flat and can vary from pale pink to deep maroon in color. In people with Klippel-Trenaunay syndrome, the port-wine stain usually covers part of one limb. The affected area may become lighter or darker with age.
Occasionally, port-wine stains develop small red blisters that break open and bleed easily.
Klippel-Trenaunay syndrome is also associated with overgrowth of bones and soft tissues beginning in infancy. Usually this abnormal growth is limited to one limb, most often one leg. However, overgrowth can also affect the arms or, rarely, the trunk.
The abnormal growth can cause pain, a feeling of heaviness, and reduced movement in the affected area. If the overgrowth causes one leg to be longer than the other, it can also lead to problems with walking.
Malformations of veins are the third major feature of Klippel-Trenaunay syndrome.
These abnormalities include varicose veins, which are swollen and twisted veins near the surface of the skin that often cause pain.
Varicose veins usually occur on the sides of the upper legs and calves. Veins deep in the limbs can also be abnormal in people with Klippel-Trenaunay syndrome.
Malformations of deep veins increase the risk of a type of clot called a deep vein thrombosis (DVT). If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening clot known as a pulmonary embolism (PE).
Complications of Klippel-Trenaunay syndrome can include a type of skin infection called cellulitis, swelling caused by a buildup of fluid (lymphedema), and internal bleeding from abnormal blood vessels. Less commonly, this condition is also associated with fusion of certain fingers or toes (syndactyly) or the presence of extra digits (polydactyly).
How common is Klippel-Trenaunay syndrome?
Klippel-Trenaunay syndrome is estimated to affect at least 1 in 100,000 people worldwide.
What genes are related to Klippel-Trenaunay syndrome?
The cause of Klippel-Trenaunay syndrome is unknown. Researchers suspect that the condition may result from changes in one or more genes that regulate the growth of blood vessels during embryonic development.
However, no associated genes have been identified. It is also unclear how blood vessel malformations are related to the overgrowth of bones and soft tissues.
How do people inherit Klippel-Trenaunay syndrome?
Klippel-Trenaunay syndrome is almost always sporadic, which means that it occurs in people with no history of the disorder in their family. Studies suggest that the condition may result from gene mutations that are not inherited.
These genetic changes, which are called somatic mutations, probably occur very early in development and are present only in certain cells. Somatic mutations could explain why the signs and symptoms of Klippel-Trenaunay syndrome are often limited to specific areas of the body.
However, it is unclear whether somatic mutations are responsible for this condition because no associated genes have been found.
What is a port-wine stain?
A port-wine stain is a certain type of hemangioma. This capillary hemangioma has a recognizable appearance. It is usually a deep violet (“port-wine”) colored lesion with fairly linear borders.
These are most often found on the affected hypertrophied limb. They are generally flat or only slightly raised compared to the surrounding unaffected skin surface. The actual depth of the lesion is unpredictable and less commonly may even affect muscle and bone.
In addition to the port-wine stain, individuals with Klippel-Trènaunay-Weber also develop varicose veins. These often can be seen at birth as a large superficial vein extending from the lower leg all the way up to the buttocks.
This vein has been referred to as the “Klippel-Trènaunay” vein and may not be obvious until later in childhood.
Occasionally affected individuals develop an arteriovenous fistula (abnormal connection between an artery and a vein). This is known as the Parkes-Weber variant of KTW. These patients usually have numerous fistulae that can result in heart failure if untreated.
What is asymmetrical limb hypertrophy?
Asymmetric limb hypertrophy is enlargement of one limb compared to the opposite side. For example, an individual with Klippel-Trènaunay-Weber syndrome may have a left leg or arm that is larger than his/her right leg or arm. This asymmetry is found in other inherited syndromes as well.
Most commonly in individuals with Klippel-Trènaunay-Weber, the leg is involved more frequently than an arm; however, on occasion there is enlargement of two limbs, a buttock, or part of the trunk of the body.
Are there other abnormalities in Klippel-Trènaunay-Weber syndrome?
Although the triad of “port-wine stain, varicosities, and asymmetric limb hypertrophy,” is the consistent clinical centerpiece of Klippel-Trènaunay-Weber, there are often other less frequent abnormalities found in those affected by the syndrome. These may include other limb or digit abnormalities such as:
- atrophy (a limb that is underdeveloped),
- fingers and toes that are disproportionately large or small,
- digits that are webbed (syndactyly),
- too many digits (polydactyly), or
- too few digits (oligodactyly).
In addition to limb abnormalities, there are some other common features, including:
- asymmetrical facial hypertrophy (one side of the face may be smaller than the other),
- macrocephaly (a large head), or
- microcephaly (a small head).
Eye problems may include glaucoma and cataracts. Any of the vascular anomalies can affect the internal organs including the intestinal and urinary tract systems.
These may be at risk for spontaneous bleeding, and it is important to evaluate any individual with evidence of superficial abdominal lesions.
Additionally, there is an increased risk of abnormal blood clots forming, which can move to the lungs, causing a pulmonary embolism.
What causes Klippel-Trènaunay-Weber syndrome?
Most cases of Klippel-Trènaunay-Weber are sporadic. They usually occur without warning, with no prior case in the family. However, there have been some cases that run in families.
What is the prognosis (outlook) with Klippel-Trènaunay-Weber syndrome?
Most persons with Klippel-Trènaunay-Weber have an enlarged leg and they do relatively well without any significant treatment. It can be helpful to wear compression stockings to prevent venous pooling in the affected extremity (varicose vein management).
However, some Klippel-Trènaunay-Weber patients do have considerable pain. Skin ulcers, infections and other skin problems can occur, but usually the treatment is conservative. Surgery is almost never needed.