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URL of this page: https://medlineplus.gov/genetics/condition/multiple-cutaneous-and-mucosal-venous-malformations/

Multiple cutaneous and mucosal venous malformations

Description

Multiple cutaneous and mucosal venous malformations (also known as VMCM) is a condition that affects the skin (cutaneous) and the moist tissues that line body cavities (mucous membranes), such as the mouth and nose. Affected individuals develop bluish patches (lesions) that represent areas where the underlying venous blood vessels developed abnormally (venous malformations). These lesions can be painful, especially when they extend from the skin into the muscles and joints.

Blood in venous malformations moves slowly, which can cause clots to form. Slow blood flow and clotting within the malformation can cause pain, swelling, and inflammation. Over time, some blood clots may harden (calcify) to form nodules called phleboliths, which can sometimes be felt underneath the skin. In people with VMCM, medical evaluation and management may be needed during pregnancy or before surgical procedures to reduce the likelihood of abnormal clotting or bleeding episodes.

Most people with VMCM are born with at least one venous malformation. As affected individuals age, the lesions that are present at birth usually become larger and new lesions often appear. The size, number, and location of venous malformations vary among affected individuals, even among members of the same family.

Frequency

VMCM appears to be a rare disorder, although its exact prevalence is unknown.

Causes

Genetic changes that cause disease or increase the risk of disease are called pathogenic variants. Pathogenic variants in the TEK gene can predispose individuals to develop venous malformations. The TEK gene provides instructions for making a type of protein called a receptor tyrosine kinase. The TEK receptor triggers the release of chemical signals that are needed for forming blood vessels (angiogenesis) and maintaining their structure. This signaling allows communication between two types of cells found within the walls of blood vessels: endothelial cells and smooth muscle cells. Communication between these two cell types is necessary to direct angiogenesis and to maintain the structure and integrity of blood vessels.

The pathogenic variants in the TEK gene that are associated with VMCM cause the TEK receptor to become overactive. Excessive signaling disrupts the normal growth and organization of endothelial cells and their interactions with the surrounding smooth muscle cells. As a result, venous blood vessels may develop abnormally, leading to the venous malformations seen in people with VMCM.

Learn more about the gene associated with Multiple cutaneous and mucosal venous malformations

Inheritance

VMCM is inherited in an autosomal dominant pattern, which means one altered copy of the TEK gene is sufficient to predispose individuals to develop venous malformations. Affected individuals typically have a parent with VMCM.

Evidence suggests that the inherited variant in the TEK gene may not always be enough to cause a particular venous malformation to develop; approximately 10 percent of people who inherit a pathogenic TEK variant do not develop visible signs of the disorder by age 20. In people with VMCM, an additional pathogenic variant in the TEK gene may arise during a person's lifetime and be present only in certain cells. This type of variant is called a somatic variant. Because the somatic variant only occurs in certain cells, it may help explain why venous malformations develop in different areas of the body and why their number and location vary among affected individuals. 

Other Names for This Condition

  • Mucocutaneous venous malformations
  • VMCM
  • VMCM1

Additional Information & Resources

Genetic Testing Information

Patient Support and Advocacy Resources

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Brouillard P, Vikkula M. Genetic causes of vascular malformations. Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R140-9. doi: 10.1093/hmg/ddm211. Epub 2007 Jul 31. Citation on PubMed
  • Limaye N, Boon LM, Vikkula M. From germline towards somatic mutations in the pathophysiology of vascular anomalies. Hum Mol Genet. 2009 Apr 15;18(R1):R65-74. doi: 10.1093/hmg/ddp002. Citation on PubMed or Free article on PubMed Central
  • Limaye N, Wouters V, Uebelhoer M, Tuominen M, Wirkkala R, Mulliken JB, Eklund L, Boon LM, Vikkula M. Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations. Nat Genet. 2009 Jan;41(1):118-24. doi: 10.1038/ng.272. Epub 2008 Dec 14. Citation on PubMed or Free article on PubMed Central
  • Morris PN, Dunmore BJ, Tadros A, Marchuk DA, Darland DC, D'Amore PA, Brindle NP. Functional analysis of a mutant form of the receptor tyrosine kinase Tie2 causing venous malformations. J Mol Med (Berl). 2005 Jan;83(1):58-63. doi: 10.1007/s00109-004-0601-9. Epub 2004 Oct 29. Citation on PubMed
  • Seront E, Boon LM, Vikkula M. TEK-Related Venous Malformations. 2008 Sep 18 [updated 2023 Mar 2]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1967/ Citation on PubMed
  • Seront E, Queisser A, Boon LM, Vikkula M. Molecular landscape and classification of vascular anomalies. Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):700-708. doi: 10.1182/hematology.2024000598. Citation on PubMed
  • Seront E, Van Damme A, Coulie J, Boon LM, Vikkula M. Current and emerging pharmacotherapies for treating vascular malformations. Expert Rev Clin Pharmacol. 2026 Apr;19(4):289-302. doi: 10.1080/17512433.2026.2641807. Epub 2026 Mar 17. Citation on PubMed
  • Soblet J, Kangas J, Natynki M, Mendola A, Helaers R, Uebelhoer M, Kaakinen M, Cordisco M, Dompmartin A, Enjolras O, Holden S, Irvine AD, Kangesu L, Leaute-Labreze C, Lanoel A, Lokmic Z, Maas S, McAleer MA, Penington A, Rieu P, Syed S, van der Vleuten C, Watson R, Fishman SJ, Mulliken JB, Eklund L, Limaye N, Boon LM, Vikkula M. Blue Rubber Bleb Nevus (BRBN) Syndrome Is Caused by Somatic TEK (TIE2) Mutations. J Invest Dermatol. 2017 Jan;137(1):207-216. doi: 10.1016/j.jid.2016.07.034. Epub 2016 Aug 9. Citation on PubMed
  • Vikkula M, Boon LM, Carraway KL 3rd, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, Mulliken JB, Olsen BR. Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell. 1996 Dec 27;87(7):1181-90. doi: 10.1016/s0092-8674(00)81814-0. Citation on PubMed

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