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Klippel-Trenaunay syndrome

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Other Names:
Klippel Trenaunay syndrome; Klippel-Trenaunay-Weber syndrome; KTW syndrome; Klippel Trenaunay syndrome; Klippel-Trenaunay-Weber syndrome; KTW syndrome; Weber-Klippel-Trenaunay; Angio-osteohypertrophy syndrome; KTS; Klippel-Trénaunay-Weber syndrome See More
Categories:
Klippel-Trenaunay syndrome (KTS) is a syndrome that affects the development of blood vessels, soft tissues, and bones. 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.[1]

Most, if not all, cases of KTS are caused by somatic mutations in the PIK3CA gene. Medical researchers believe KTS is part of a group of disorders known as PIK3CA-related overgrowth spectrum (PROS) which also includes MCAP and CLOVES syndromes, hemimegalencephaly, fibroadipose hyperplasia, and epidermal nevus.[1][2][3] Treatment is symptomatic and supportive.
Last updated: 5/23/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 45 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Cavernous hemangioma
Collection of dilated blood vessels that forms mass
0001048
Cutis marmorata 0000965
Finger syndactyly 0006101
Glaucoma 0000501
Hand oligodactyly
Hand has less than 5 fingers
0001180
Hemihypertrophy of upper limb
Overgrowth of one arm
0100554
Large face
Big face
0100729
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Scoliosis 0002650
Skin ulcer
Open skin sore
0200042
Venous insufficiency
Poorly functioning veins
0005293
Visceral angiomatosis 0100761
30%-79% of people have these symptoms
Abnormality of coagulation 0001928
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment
[ more ] 		0100543
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Hand polydactyly
Extra finger
0001161
Multiple lipomas
Multiple fatty lumps
0001012
Seizure 0001250
Tricuspid valve prolapse 0001704
5%-29% of people have these symptoms
Abnormality of the menstrual cycle 0000140
Bone pain 0002653
Cellulitis
Bacterial infection of skin
Skin infection
[ more ] 		0100658
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure
[ more ] 		0001635
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face
[ more ] 		0000324
Hematuria
Blood in urine
0000790
Hemihypertrophy of lower limb
Overgrowth of one leg
0100553
Hyperpigmented nevi 0007481
Lymphedema
Swelling caused by excess lymph fluid under skin
0001004
Macrodactyly
Finger overgrowth
0004099
Peripheral arteriovenous fistula 0100784
Pulmonary embolism
Blood clot in artery of lung
0002204
Tall stature
Increased body height
0000098
Telangiectasia of the skin 0100585
Venous thrombosis
Blood clot in vein
0004936
Percent of people who have these symptoms is not available through HPO
Abnormality of blood and blood-forming tissues 0001871
Arteriovenous fistula 0004947
Hemangioma
Strawberry mark
0001028
Hemihypertrophy
Asymmetric overgrowth
0001528
Hyperpigmented nevi and streak 0005606
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Lymphangioma 0100764
Sporadic
No previous family history
0003745
Syndactyly
Webbed fingers or toes
0001159
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Last updated: 7/1/2020
Most cases of KTS are caused by mutations in the PIK3CA gene. However, the mutation in the gene is not present in every cell of the body and is not inherited or passed down from either parent. The type of genetic mutation which causes KTS is called a somatic mutation.[1][2][3] These somatic mutations occur after conception (after the egg and sperm join together), but probably happen very early in development. Since somatic mutations are only present in some of the body's cells, the signs and symptoms of KTS usually only affect specific areas of the body.[1][2][3] The PIK3CA gene provides instructions for making a protein which is part of an enzyme that is important for cell growth and division (proliferation), movement (migration) of cells, and cell survival. Mutations in the PIK3CA gene result in increased cell proliferation leading to abnormal growth of the bones, soft tissues, and blood vessels.[1]

Some researchers believe all KTS is caused by somatic mutations in the PIK3CA gene and when a mutation cannot be found, the person may actually have a different disorder.[2] Other researchers believe KTS can be caused by mutations in other yet to be discovered genes.[1][3]
Last updated: 5/24/2017
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.[1][4]
Last updated: 5/24/2017
There is no cure for KTS.[5][6] Treatment is symptomatic and supportive.[5] Conservative treatments seem most effective while limiting the chances for undesired side effects.[6] 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.[5][6] 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.[5][6] 
Last updated: 5/25/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis should include venous dysplasias, lymphedema and bone tumors.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.
  • ClinicalTrials.gov lists trials that are related to Klippel-Trenaunay syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Klippel-Trenaunay syndrome. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Klippel-Trenaunay syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • At an adult age, can this syndrome cause pain in the limb that has abnormal growth? See answer

  • Is there a cure or treatment for this condition? See answer


  1. Klippel-Tranaunay Syndrome. Genetics Home Reference. 2016; http://www.ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome.
  2. Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC 3rd, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, and Murillo R. Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. Journal of Pediatrics. April 2015; 166(4):1048-54. http://www.ncbi.nlm.nih.gov/pubmed/25681199.
  3. Vahidnezhad H, Youssefian L, and Uitto J. Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). Experimental Dermatology. Januaray 2016; 25(1):17-19. http://www.ncbi.nlm.nih.gov/pubmed/26268729.
  4. Mirzaa G, Conway R,Graham JM, and Dobyns WB.. PIK3CA-Related Segmental Overgrowth. GeneReviews. August 15 2013; https://www.ncbi.nlm.nih.gov/books/NBK153722/.
  5. NINDS Klippel-Trenaunay Syndrome (KTS) Information Page. National Institute of Neurological Disorders and Stroke (NINDS). September 30 2011; https://www.ninds.nih.gov/Disorders/All-Disorders/Klippel-Trenaunay-Syndrome-KTS-Information-Page.
  6. About K-T: Management and Treatments. Klippel Trenaunay (KT) Support Group. https://k-t.org/about-kt/management-and-treatments. Accessed 11/11/2014.