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Diseases

Genetic and Rare Diseases Information Center (GARD)

Klippel-Trenaunay syndrome


Other Names for this Disease
  • Klippel Trenaunay syndrome
  • Klippel-Trenaunay-Weber syndrome
  • KTW syndrome
  • Weber-Klippel-Trenaunay
  • Angio-osteohypertrophy syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

How does Klippel Trenaunay syndrome (KTS) occur? How, if it is not inherited, does it come about? Which gene is associated with it? 

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What causes Klippel-Trenaunay syndrome?

The underlying cause of Klippel-Trenaunay syndrome (KTS) is currently unknown.[1] There have been many theories about what may cause this condition, including:
  • paradominant inheritance - a theory that may explain occasional familial cases of sporadic conditions. This theory proposes that a person may inherit a mutation in one copy of a gene responsible for a condition, but another, acquired mutation (somatic mutation) must occur in the other copy of the gene after conception for a person to develop signs and symptoms.
  • somatic mosaicism of an otherwise dominant lethal gene
  • disturbance of blood vessel formation (vasculogenesis) in the embryonic period
  • defects in the mesoderm (one of three layers of an embryo, which gives rise to structures including connective tissue, muscle, and bone)
  • various chromosomal translocations and mutations - there have been case reports of these, but none of them have been proven to have any definite association with the condition.[1]
However recently, medical researchers have found multiple cases of KTS associated with mutations in the PIK3CA gene.[2][3]  Some researchers believe all KTS is likely caused by mutations in this gene and when a mutation cannot be found, the affected person may actually have a different condition such as Beckwith-Wiedemann syndrome.[2]  More research studies will need to be completed to reach a consensus among medical researchers. 
Last updated: 2/9/2016

If Klippel Trenaunay syndrome (KTS) is not inherited, how does it come about?

Studies suggest that KTS may result from gene mutations that are not inherited. These genetic changes, which are called somatic mutations, probably occur very early in development and are present only in certain cells. Somatic mutations could explain why the signs and symptoms of KTS are often limited to specific areas of the body.[4]
Last updated: 1/10/2012

Which gene is associated with Klippel Trenaunay syndrome (KTS)?

Researchers suspect that KTS may result from changes in one or more genes that regulate the growth of blood vessels during embryonic development. However, to date, no associated genes have been identified.[4]
Last updated: 1/10/2012

References
  • Sharma D, Lamba S, Pandita A, Shastri S. Klippel-trénaunay syndrome - a very rare and interesting syndrome. Clin Med Insights Circ Respir Pulm Med. March 5, 2015; 9:1-4.
  • 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.
  • 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.
  • Klippel-Tranaunay Syndrome. Genetics Home Reference. July 2010; http://www.ghr.nlm.nih.gov/condition/klippel-trenaunay-syndrome.
Other Names for this Disease
  • Klippel Trenaunay syndrome
  • Klippel-Trenaunay-Weber syndrome
  • KTW syndrome
  • Weber-Klippel-Trenaunay
  • Angio-osteohypertrophy syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.