Klippel-Trenaunay-Weber Syndrome

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Klippel-Trenaunay-Weber syndrome

Definition

Klippel-Trenaunay-Weber syndrome (KTWS) is most often defined by the presence of three classic characteristics: vascular abnormalities, prominent varicose veins or darkened skin patches, and limb enlargement.

Description

KTWS was first described by Drs. Klippel and Trenaunay in 1900. The condition is also known by the names Klippel-Trenaunay syndrome (KTS) and Angioosteohypertrophy syndrome.

Vascular abnormalities in KTWS may involve the capillary, venous, arterial, and lymphatic systems. Limb enlargement resulting in asymmetry of the limbs is quite common. This usually affects the lower limbs, but occasionally the upper limbs as well. Vein enlargement and varicose veins are also typically a part of KTWS. Other occasional abnormalities in KTWS may involve the fingers and toes, other skin changes, glaucoma , mental delays, seizures, and blood platelet problems.

Genetic profile

In most cases, KTWS occurs by chance alone. There is usually no family history and very little chance of the condition occurring again, even to the same parents. In 2004, researchers reported that abnormalities in the VG5Q gene on chromosome 5 were found to cause a susceptibility to KTWS. VG5Q is a gene known to be important for blood vessel development, so abnormalities within it might naturally lead to some symptoms of KTWS.

A few families with multiple people who may have KTWS have been noted. Ceballos-Quintal, et al., described a family with three people who were suspected to have KTWS, in three separate generations. Each person had different symptoms seen in KTWS. This family history suggests autosomal dominant inheritance in rare cases of KTWS. In dominant inheritance, an affected individual has a 50% chance of having an affected child with KTWS, regardless of that child's gender. It is also common to see families with histories of the condition in this type of inheritance pattern.

Demographics

KTWS is a relatively uncommon condition that is found worldwide, affecting males and females equally. Additionally, it appears to affect people of all ages, though the average age that children may come for medical care is four years.

Signs and symptoms

Vascular abnormalities

Problems may occur as a result of an abnormal communication between a group of blood vessels and the skin. An abnormal grouping of blood vessels may reach the skin, causing the appearance of a large hemangioma on the skin. Additionally, the blood vessel walls may enlarge or swell, causing large, blood-filled spaces within the body. Internal bleeding can be a serious complication in some cases. There may also be swelling or masses of tissue from problems in the lymphatic system. These may disturb neighboring tissues and internal organs.

Veins and arteries may join abnormally, which can cause an improper flow of blood between the body's vein and artery systems. The deep veins can be incorrectly developed, sometimes being smaller than usual or even duplicated. Ultimately, this can disrupt the proper circulation of blood between various parts of the body.

Varicose veins are common in KTWS. People may have prominent veins that involve their feet or entire legs.

The lymphatic system, meant to help blood and fluid circulate, can be problematic in those with KTWS. Lymphatic fluid can collect abnormally, causing an enlargement and swelling of surrounding tissues. Smaller swellings can occur in various parts of the body like the neck, armpits, or other locations where the lymph nodes are naturally located.

Skin abnormalities

Abnormal capillary formations can cause dark patches on the skin, which look similar to a hemangioma. These are usually reddish in color and can be large. They are most often seen on the lower limbs, but in 17–21% of people with KTWS the entire limb or one side of the body is affected. The dark skin patches usually have an irregular and linear border to them. When seen on the torso of someone's body, they do not usually cross from the left to right sides. Other skin abnormalities can include smaller streaks and patches of dark skin.

Limb abnormalities

Limb enlargement is a very common sign of KTWS. In the vast majority of people, one leg is larger than the other. In others, an arm or a combination of both the arm and leg are affected. About 70% of people with KTWS have lengthening of an extremity, and an increase in thickness occurs in at least 50%.

Enlargement and vascular abnormalities usually occur together in the same limb. The enlargement of the limbs is presumed to be due to a combination of factors: underlying bone overgrowth, lymphatic swelling, muscle overgrowth, and thickened skin.

Other limb abnormalities can include enlargement of the fingers or toes, webbing between these digits, extra digits, or missing digits.

Other signs of KTWS

Glaucoma can be seen in KTWS, either first appearing at birth or in early childhood. Seizures can be part of the condition and, rarely, mental retardation as well.

Individuals with extensive vein or lymphatic abnormalities can develop a blood-clotting problem in which their platelet count is lower than usual. This is sometimes incorrectly referred to as the Kasabach-Merritt syndrome, which actually occurs when the blood platelet count is extremely low.

Diagnosis

As of early 2005, there is no clinical genetic testing available for KTWS. Research taking place in the United States and Belgium offers screening of genes that may be implicated in the condition, but it is only offered as part of a research study. Most people with KTWS are diagnosed because of signs and symptoms they have.

Children may first come to medical attention for KTWS at birth or shortly afterward because they are born with dark patches on their skin or a limb that is larger than the other. A careful evaluation by a team of physicians, including a pediatrician, medical geneticist, and a dermatologist, can help to identify whether the diagnosis is KTWS.

KTWS has occasionally been suspected during a pregnancy in cases where significant limb enlargement was seen on a prenatal ultrasound . Roberts, et al., reported a case from 1999 where a prenatal ultrasound showed that the developing baby had limb and digit enlargement with increased blood flow and fluid-filled sacs.

In this case, suspecting KTWS helped to determine the best type of delivery for the baby and the mother. The baby was born by a Caesarean section, which helped reduce the complications to him and his mother from his limb enlargement and fluid collections. When the baby was born, he was found to have large red skin patches on the affected limb, and KTWS was highly suspected.

There are symptoms of KTWS that overlap with other conditions. Sturge-Weber syndrome usually has dark skin patches and vascular abnormalities, glaucoma, seizures, and mental delays. However, significant limb enlargement is not usually a part of Sturge-Weber syndrome.

Parkes-Weber syndrome involves vascular abnormalities, but these differ from those seen in KTWS. For example, Parkes-Weber syndrome does not usually involve the lymphatic system. Additionally, Parkes-Weber syndrome can have symptoms that affect the heart, which are not typically seen in KTWS.

Treatment and management

There is no known cure for KTWS. However, treatments are available to help with some symptoms of the condition. These typically involve a large team of specialists that may include a pediatrician, vascular surgeon, orthopedist, orthopedic surgeon, hematologist, medical geneticist, genetic counselor, ophthalmologist, neurologist, social worker, and therapist.

Custom-made compression stockings can be worn to reduce swelling, create a barrier for minor trauma, and help blood drain from an enlarged body part. Parents can find it a challenge to encourage a young child to wear such stockings, but they may work well for older children and adults. Compression stockings do not usually permanently reduce the size of the enlarged limb.

Swelling can also be reduced with manual drainage, a gentle massage of the affected area. A physical therapist, occupational therapist, or massage therapist typically performs this. Air-driven pumps can also help reduce swelling. The affected limb is covered in an air-filled plastic sleeve, which places gentle pressure to stimulate fluid movement from the swollen limb.

Some people have seen reduction in the redness of their skin patches through laser treatments using pulses of light. It may require a series of these treatments, and skin changes may still be noticeable or even unchanged after the treatment is finished.

If there is increased bleeding or a low amount of platelets is suspected, blood testing can check the platelet level. This can be carefully monitored through a series of blood tests, and in some cases a blood transfusion may be required. If a patient has internal bleeding that causes damage to some internal organs or tissues, surgery to control this bleeding or remove affected tissues may be needed.

In some cases, bacterial infections can warrant the use of antibiotics to stop the infection.

Ultrasounds, x rays, magnetic resonance imaging (MRI) scans, lymphoscintigraphy, and angiography can help obtain details about limb enlargement. These all attempt to gain information about the specific tissues or organs affected by limb enlargement and abnormal blood flow.

Surgical treatments may be needed for some with KTWS, though the goal is often to avoid this whenever possible. Abnormal blood vessels may need to be repaired by removing them or rejoining them. Varicose veins may need to be removed, but these can sometimes return even after treatment. Women with KTWS who are pregnant may have bleeding complications depending on the location of any vascular abnormalities, and should be monitored closely during their pregnancies.

Minor leg length differences can sometimes be treated with a shoe insert that is worn on the foot of the shorter leg. If a leg causes a significant asymmetry, a procedure called epiphysiodesis may be necessary. This surgical treatment can stop bone growth in an affected leg, but requires destroying a portion of the underlying bone to do it. It must be timed well to coordinate with the normal bone growth that occurs in childhood and adolescence.

In rare cases, limb or digit amputation may be needed to improve function for a person with KTWS. This is typically done when other helpful options have not been successful.

Seizures can occur in KTWS, and these may be treated with anti-seizure medications. Glaucoma may be identified from a careful eye examination and treated with eye drops, pills, ointments, or laser therapy to reduce the pressure in the eye and maintain vision.

Mental retardation is rare in KTWS, but may be assessed by a child development team or early childhood program. Extra assistance is sometimes available through early intervention programs and special education in schools. Social workers are useful to connect families to helpful resources.

A psychologist, genetic counselor, or therapist can be helpful for some with KTWS. Living with visible skin changes can be difficult, and some may find it easier to talk to an objective person or to talk with other affected families in a support group.

Prognosis

Prognosis can vary widely in KTWS. Complications, especially the vascular abnormalities, can be serious and cause death if symptoms are severe enough and treatment is not successful. The exact expected lifespan for the average person with KTWS is not known, but is highly dependent on the symptoms experienced.

The best way to increase one's prognosis is to utilize a team of specialists that is familiar with KTWS. Through early identification and monitoring of symptoms, treatments can be started sooner and appropriate medical decisions can be made to help the individual and the family.