Rare Pulmonology News

Disease Profile

Klippel-Trenaunay syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

US Estimated

Europe Estimated

Age of onset

Infancy

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ICD-10

Q87.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Klippel Trenaunay syndrome; Klippel-Trenaunay-Weber syndrome; KTW syndrome;

Categories

Blood Diseases; Congenital and Genetic Diseases; Musculoskeletal Diseases;

Summary

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.

Symptoms

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.

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
Do you have updated information on this disease? We want to hear from you.

Cause

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]

Treatment

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]

Organizations

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

    Organizations Providing General Support

      Learn more

      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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Klippel-Trenaunay syndrome. This website is maintained by the National Library of Medicine.
      • 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.

          References

          1. Klippel-Tranaunay Syndrome. Genetics Home Reference. 2016; https://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. https://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. https://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.

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