Klippel-Trenaunay syndrome

Alternate names

Klippel Trenaunay syndrome; Klippel-Trenaunay-Weber syndrome; KTW syndrome; Weber-Klippel-Trenaunay; Angio-osteohypertrophy syndrome; KTS; Klippel-Trénaunay-Weber syndrome

Definition

Klippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues (such as skin and muscles), 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.

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Epidemiology

Klippel-Trenaunay syndrome is estimated to affect at least 1 in 100,000 people worldwide.

Cause

• Klippel-Trenaunay syndrome can be caused by mutations in the PIK3CA gene.
• This gene provides instructions for making the p110 alpha (p110α) protein, which is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K).
• PI3K plays a role in chemical signaling that is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, and cell survival.
• These functions make PI3K important for the development of tissues throughout the body.

Gene mutations

• The PIK3CA gene mutations associated with Klippel-Trenaunay syndrome alter the p110α protein.
• The altered subunit makes PI3K abnormally active, which allows cells to grow and divide continuously.
• Increased cell proliferation leads to abnormal growth of the bones, soft tissues, and blood vessels.
• Klippel-Trenaunay syndrome is one of several overgrowth syndromes, including megalencephaly-capillary malformation syndrome, that are caused by mutations in the PIK3CA gene. Together, these conditions are known as the PIK3CA-related overgrowth spectrum (PROS).
• Because not everyone with Klippel-Trenaunay syndrome has a mutation in the PIK3CA gene, it is possible that mutations in unidentified genes may also cause this condition.

Inheritance

• KTS is not known to be inherited. Since KTS is caused by somatic mutations and this type of mutation is not present in every cell of the body, the risk a child to be born with KTS to a parent with KTS is similar to the general population risk.
• In other words, children of a parent with KTS have the same risk of having KTS as someone whose parents do not have KTS. As far as we know, there are no confirmed reported cases of KTS being passed down to the children of a person with KTS.

Signs and symptoms

• This syndrome has three characteristic features: a red birthmark called a port-wine stain, overgrowth of soft tissues and bones, and vein malformations such as varicose veins or malformations of deep veins in the limbs.
• The overgrowth of bones and soft tissues usually begins in infancy and is most often only affects one leg.
• However, it can also affect the arms or sometimes the upper body area (torso).
• The overgrowth can cause pain, a feeling of heaviness, and make the affected leg (or arm) hard to move.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Cataract(Clouding of the lens of the eye)
• Cavernous hemangioma(Collection of dilated blood vessels that forms mass)
• Cutis marmorata
• Finger syndactyly
• Glaucoma
• Hand oligodactyly(Hand has less than 5 fingers)
• Hemihypertrophy of upper limb(Overgrowth of one arm)
• Large face(Big face)
• Macrocephaly(Increased size of skull)
• Microcephaly(Abnormally small skull)
• Scoliosis
• Skin ulcer(Open skin sore)
• Venous insufficiency(Poorly functioning veins)
• Visceral angiomatosis

30%-79% of people have these symptoms

• Abnormality of coagulation
• Cognitive impairment(Abnormality of cognition)
• Gastrointestinal hemorrhage(Gastrointestinal bleeding)
• Hand polydactyly(Extra finger)
• Multiple lipomas(Multiple fatty lumps)
• Seizure
• Tricuspid valve prolapse

5%-29% of people have these symptoms

• Abnormality of the menstrual cycle
• Bone pain
• Cellulitis(Bacterial infection of skin)
• Congestive heart failure(Cardiac failure)
• Facial asymmetry(Asymmetry of face)
• Hematuria(Blood in urine)
• Hemihypertrophy of lower limb(Overgrowth of one leg)
• Hyperpigmented nevi
• Lymphedema(Swelling caused by excess lymph fluid under skin)
• Macrodactyly(Finger overgrowth)
• Peripheral arteriovenous fistula
• Pulmonary embolism(Blood clot in artery of lung)
• Tall stature(Increased body height)
• Telangiectasia of the skin
• Venous thrombosis(Blood clot in vein)

Diagnosis

Patients are diagnosed on the basis of physical findings, sometimes with supportive imaging, of commonly a segmental anomaly with a cutaneous port-wine stain, lymphatic and venous malformations and overgrowth..

Treatment

• There is no cure for KTS.
• Treatment is symptomatic and supportive.
• Conservative treatments seem most effective while limiting the chances for undesired side effects.
• This may include the use of elastic garments and pumps to relieve lymphedema and protect limbs from trauma or orthopedic devices for discrepancies in limb length.
• Laser therapy may be used to diminish or eliminate some skin lesions (port-wine stains).
• Surgery may be used for tissue debulking, vein repair, or to correct uneven growth in the limbs.

Prognosis

KTS is often a progressive disorder, and complications may be life-threatening. However, many individuals can live well while managing their symptoms.

NIH genetic and rare disease info

• NIH info on Klippel-Trenaunay syndrome

Klippel-Trenaunay syndrome is a rare disease.

Klippel-Trenaunay syndrome Resources
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