What is Klippel-Trenaunay-Weber Syndrome?
Klippel Trenaunay syndrome (KTS) is a medical condition where there are abnormal growths and changes in the skin’s blood vessels, veins, and lymphatic system (the body’s disease-fighting network). These changes also result in the unusual enlargement of soft tissues and bones in the affected body part. Another term for this syndrome is capillary-lymphatic-venous malformation (CLVM), which describes the changes seen in these vessels.
This condition was first highlighted in 1900 by two French doctors named Maurice Klippel and Paul Trenaunay. KTS is usually diagnosed when a person shows at least two of the three key signs: distorted skin capillaries (small blood vessels), venous irregularities, and an enlarged limb. It’s important to understand that the presence of arteriovenous malformations (abnormal connections between arteries and veins) creates a separate condition called Parkes-Weber syndrome, which is different from KTS.
What Causes Klippel-Trenaunay-Weber Syndrome?
Recent research has discovered a connection between the root cause of Klippel Trenaunay syndrome and changes in a specific gene known as PIK3CA. This gene mutation triggers a chain reaction that ultimately leads to abnormal growth of cells, as it disrupts the body’s normal growth pathway called mTORC2.
These gene changes usually occur during the early stages of embryo development, particularly when blood vessels are forming, which explains the symptoms seen in this condition.
Klippel Trenaunay syndrome is now classified with other disorders that cause abnormal growth under a group known as PIK3CA-related overgrowth spectrum (PROS). These conditions all involve changes to the same PIK3CA gene and can have similar symptoms.
Lastly, in some rare cases, part of the genetic material or chromosomes (parts of human cells that carry genetic information) specifically involving chromosomes number 5 and 11, and 8 and 14, have been seen to swap places. This rearrangement is also associated with the condition.
Risk Factors and Frequency for Klippel-Trenaunay-Weber Syndrome
The estimated occurrence rate of this condition is 2 to 5 in every 100,000 people, and it affects both men and women equally.
Signs and Symptoms of Klippel-Trenaunay-Weber Syndrome
Klippel Trenaunay syndrome is a condition that affects different parts of the body, like the blood vessels, tissues, and bones. These parts can grow more than they should. Most of the time, this condition affects only one of the legs, but it can also affect the arms, head, and neck. Here are some symptoms typically seen:
- Capillary issues: Reddish or purple birthmarks known as port-wine stains. These birthmarks appear on 90-100% of the patients and grow as the child matures.
- Vein malformations: Varicose veins and embryonic veins are observed in 70-100% of the patients. In some cases, these can lead to gastrointestinal bleeds.
- Lymphatic malformations: Occurring in 15-50% of patients, these include swelling and fluid-filled sacs.
- Musculoskeletal findings: Tissues and bones in one limb may grow to be larger than the other, leading to a difference in limb length.
- Other rare findings: Seizures, developmental delays, urinary abnormalities presenting as blood in urine, syndactyly (fused fingers or toes), polydactyly (extra fingers or toes), and clinodactyly (curved finger).
Testing for Klippel-Trenaunay-Weber Syndrome
Klippel Trenaunay syndrome is a condition that is diagnosed by checking for two out of three classic features. It is recommended that imaging tests are used to evaluate problems with the veins, lymphatic systems, soft tissues and bone growth, as well as to understand how far the disease has spread and what complications have occurred.
As a first step, a type of ultrasound called a color doppler can be used to check for abnormalities such as widened, swollen veins (varicosities), issues with the veins themselves (venous malformation) or if a clot has formed (thrombus). However, MRI scans (which use magnetic fields to create detailed images of the body) and MRV scans (which specifically look at the veins) can give a clearer picture of all the problems that exist due to the disease.
Most patients with Klippel Trenaunay syndrome have high levels of something called D-dimer in their blood; this is a substance that is usually present when a blood clot has dissolved, which can happen often in this disease.
Treatment Options for Klippel-Trenaunay-Weber Syndrome
In patients with Klippel Trenaunay syndrome, a condition characterized by blood vessel malformations, varicose veins, and overgrowth of bones and soft tissues, the care of a team of different healthcare providers is usually the best approach. The primary form of treatment is managing symptoms with medication, with surgery only needed in a few cases.
Keeping the skin healthy is crucial to avoid skin infections and bleeding caused by scratching. We also need to keep a close eye on children for any differences in limb length and refer them to bone doctors for braces or surgery if needed. Items like compression socks, raising the limb, and devices that apply intermittent pressure are used to reduce swelling caused by a build-up of lymph fluid and poor vein function.
We can also use a procedure called sclerotherapy, which involves injecting a solution into the blood vessels to shrink them, and has shown good results for treating malformations of capillaries, veins and lymph vessels.
Laser treatment is an option for treating port-wine stains, which are reddish to purplish discolorations on the skin.
Surgery is used only for cases that don’t respond to medication. It typically involves closing off abnormal blood vessels and removing severe varicose veins. Birth control pills containing estrogen are not recommended due to their potential to cause blood clots.
Pregnant patients require medication to prevent blood clots, as they are at high risk of deep vein thrombosis (clotting in the deep veins of the leg) and pulmonary embolism (a blood clot in the lungs). Bleeding due to blood clotting disorders should be quickly identified and treated with supportive care and certain medications like fresh frozen plasma, and a type of blood thinner called low molecular weight heparin. Before undergoing surgery, patients should receive this blood thinner to reduce the risk of blood clotting inside the blood vessels.
Rapamycin is a new therapy that can halt the growth of abnormal blood vessels and improve quality of life in patients with Klippel Trenaunay syndrome. This drug works by blocking a pathway within cells that contributes to tissue overgrowth. Patients taking this medication need close monitoring for side effects and toxicities, such as abnormalities in blood counts and lipid levels.
What else can Klippel-Trenaunay-Weber Syndrome be?
Klippel Trenaunay syndrome, a condition that affects the development of blood vessels, skin, and bones, is often confused with other conditions that result in uneven growth and skin abnormalities. The following conditions should also be taken into account during diagnosis:
- CLOVES: a condition that leads to fatty overgrowth, skin abnormalities, and bone malformations.
- MCAP syndrome: a condition causing brain overgrowth and capillary malformations.
- DCMO: a condition characterized by excessive blood vessel growth and overgrowth.
- FAO: a disorder that results in fibro adipose overgrowth.
- Proteus syndrome: a condition characterized by the overgrowth of skin, bones, and connective tissues after birth.
- Beckwith-Wiedemann syndrome: a disease marked by uneven growth, low blood sugar at birth, abnormal ear structure, and abdominal wall defects.
- Maffucci Syndrome: this condition involves the development of multiple benign growths in the bone cartilage.
- Plexiform neurofibromatosis: This condition, associated with Neurofibromatosis Type 1 (NF-1), leads to areas of overgrowth.
It’s also important to differentiate Klippel Trenaunay syndrome from Parkes-Weber syndrome, as these two conditions can be mistaken for each other. Parkes-Weber syndrome shares some similarities but is primarily characterized by the overgrowth of soft tissue and bones and high-flow blood vessel malformations.
What to expect with Klippel-Trenaunay-Weber Syndrome
Klippel Trenaunay syndrome is a complex condition with a range of symptoms. The seriousness of this syndrome is largely tied to the severity of abnormal blood vessels (vascular malformations) in the body. Over time, these malformations can grow and cause worsened vein insufficiency – meaning that the veins struggle more and more to pump blood back to the heart.
One potential complication of this syndrome is severe bleeding from malformations in the digestive system, or GI tract. This situation can become life-threatening if not treated quickly, as it may lead to excessive blood loss.
Another complication can arise from recurrent deep vein thrombosis, or serious blood clots. These blood clots can lead to a pulmonary embolism, which is a blockage in the lungs. This blockage can be severe and potentially fatal.
Possible Complications When Diagnosed with Klippel-Trenaunay-Weber Syndrome
Cellulitis, or a skin infection, can occur in a limb affected by poor blood flow or the leaking of lymphatic fluid, often due to neglecting skincare. This condition could potentially result in sepsis, a life-threatening infection that spreads throughout the body.
Patients with KTS (Klippel-Trenaunay Syndrome) have an increased risk of local blood clotting, observed through high D-dimer levels, a sign of abnormal blood clotting. These high levels are typically caused by vascular and lymphatic abnormalities.
Moreover, bleeding from blood vessel malformations in the gastrointestinal tract can range from chronic, hidden bleeding that requires numerous blood transfusions and iron supplements, to severe, life-threatening bleeding that can cause disseminated intravascular coagulation (or DIC), a condition causing small blood clots throughout the body that can lead to organ damage.
Furthermore, repeated occurrences of pulmonary embolism, resulting from deep vein thrombosis, can lead to long-term changes in small blood vessels. This can cause pulmonary hypertension, a type of high blood pressure that affects the arteries in the lungs and the right side of the heart.
Lastly, if a limb excessively grows in size, which can occur in persons with KTS, it may require reduction surgeries to improve mobility and walking abilities.
Common Conditions:
- Cellulitis leading to sepsis
- Increased risk of local blood flow abnormalities
- Gastrointestinal bleeding ranging from chronic to severe
- Disseminated intravascular coagulation (DIC)
- Recurrent pulmonary embolism leading to pulmonary hypertension
- Limb hypertrophy requiring reduction surgery
Preventing Klippel-Trenaunay-Weber Syndrome
If you or your child has been diagnosed with Klippel-Trenaunay syndrome, it’s important to understand that this condition can get worse over time. Klippel-Trenaunay syndrome is a rare condition that affects the development of blood vessels, soft tissues, and the growth of bones. This could lead to complications, which is why regular check-ups are crucial. You or your child’s doctor will keep an eye on any signs that one leg might be growing longer than the other, and manage the problem as soon as possible.
It’s also crucial to take good care of your skin to prevent infections. This is because Klippel-Trenaunay syndrome can cause changes in the skin that can make it more susceptible to infections.
For those planning to have surgery, it’s important to know that you might need to start taking medicine to prevent blood clots two weeks before your procedure. This is to ensure that you don’t develop dangerous clots in your blood vessels during or after surgery.
Lastly, if you are pregnant, please know that you carry a higher risk of developing blood clots. So, your pregnancy will be closely watched by your healthcare provider.
Also, if you or your child has sudden bleeding in the stomach or intestines, seek immediate medical attention. This is because Klippel-Trenaunay syndrome can cause abnormalities in the blood vessels that can lead to severe bleeding.
