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Multiple cutaneous/mucosal venous malformation
This condition causes benign (non-cancerous) growths of abnormally formed veins, typically appearing on the skin and lining of internal surfaces. It is present from birth, though lesions may grow larger over time, and is caused by changes in the TEK gene.
Overview
Multiple cutaneous/mucosal venous malformation (VMCM) is a rare genetic condition that primarily affects the blood vessels, specifically the veins. Individuals with VMCM develop multiple venous malformations, which are abnormal clusters of veins that are present at birth [PMID:18491295]. These malformations are benign, meaning they are not cancerous, and they typically appear as soft, compressible blue or purple lumps on the skin and mucous membranes, such as the lining of the mouth, nose, or digestive tract.
These lesions can vary in size and number, ranging from a few small spots to many larger, disfiguring masses. While the malformations are present from birth, they often become more noticeable or grow larger during childhood and adolescence, particularly during periods of hormonal change like puberty or pregnancy [PMID:30138406]. Though generally not life-threatening, their location and size can sometimes cause pain, functional issues, or cosmetic concerns.
Symptoms & clinical features
The main clinical features of multiple cutaneous/mucosal venous malformation are the visible lesions themselves. These venous malformations are typically soft to the touch and can be easily compressed, refilling when pressure is released. Their colour often ranges from blue to purple, reflecting the deoxygenated blood within the abnormal veins. They can appear anywhere on the skin, but are frequently found on the trunk and limbs.
In addition to the skin, venous malformations can affect mucous membranes, including those in the mouth, nasal passages, and gastrointestinal tract. Depending on their location, these internal malformations can lead to various symptoms. For example, lesions in the mouth may cause discomfort or interfere with speech and eating. Those in the gastrointestinal tract might lead to episodes of bleeding, which could manifest as blood in stool or anaemia [PMID:18491295]. Pain is a common symptom, especially if the malformations are subject to trauma or blood clots form within them.
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Affected organs
The primary organs and tissues affected in multiple cutaneous/mucosal venous malformation are the skin and various mucous membranes throughout the body. On the skin, lesions can appear anywhere, often as soft, blue or purple masses. Mucous membranes, which line many internal body cavities and organs, are also commonly involved. This includes the lining of the mouth, nasal passages, and throat.
Less commonly, but with potential for more significant impact, venous malformations can also occur within the gastrointestinal tract (oesophagus, stomach, intestines), which may lead to chronic bleeding and associated iron-deficiency anaemia. Occasionally, malformations have been noted in other internal organs or tissues, though this is less typical than skin and mucosal involvement.
Risks & severity
The severity of multiple cutaneous/mucosal venous malformation can vary considerably between individuals. While the malformations are benign, they can pose challenges depending on their size, number, and location. Lesions in visible areas like the face or mouth can lead to cosmetic concerns and psychological distress. Those located internally, particularly in the gastrointestinal tract, carry a risk of bleeding, which, if chronic, can lead to anaemia requiring medical attention.
The malformations are present from birth, but their size and prominence may increase over time, particularly during puberty or pregnancy, due to hormonal influences [PMID:30138406]. Complications can include pain, particularly if blood clots (thrombosis) form within the malformations, or if they are subject to repeated trauma. The condition is not typically life-shortening, but ongoing management may be required for symptoms and complications.
Genetic causes
Multiple cutaneous/mucosal venous malformation is caused by pathogenic changes in the TEK gene. The TEK gene provides instructions for making a protein called Tie2, which is a receptor tyrosine kinase. This protein plays a critical role in the development and maintenance of blood vessels, particularly veins [PMID:18491295]. Tie2 helps regulate how endothelial cells (cells that line blood vessels) grow, survive, and form new vessels.
Pathogenic variants in the TEK gene can lead to an overactive Tie2 protein. This overactivity disrupts the normal signalling pathways involved in blood vessel formation, leading to the abnormal development and growth of veins that characterise venous malformations. These genetic changes are typically missense variants, meaning they result in a single amino acid change in the Tie2 protein, leading to its abnormal function.
- TEK TEK receptor tyrosine kinase
Inheritance pattern
Multiple cutaneous/mucosal venous malformation is inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of the altered TEK gene from either parent to develop the condition. If one parent has the condition, there is a 50% chance with each pregnancy that their child will also inherit the altered gene and develop the condition, regardless of the child's sex.
In some cases, a new pathogenic variant in the TEK gene can occur spontaneously in an individual (a 'de novo' variant) with no family history of the condition. In such instances, while the affected individual would have a 50% chance of passing it on to their children, their parents would typically not be affected.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of multiple cutaneous/mucosal venous malformation is often initiated based on characteristic clinical findings, such as the presence of multiple soft, compressible blue or purple lesions on the skin and mucous membranes. Imaging techniques, such as ultrasound or MRI, may be used to further characterise the malformations, assess their extent, and rule out other types of vascular lesions.
Confirmation of the diagnosis typically involves genetic testing to identify a pathogenic variant in the TEK gene. Referral to a clinical genetics service is the usual pathway for this. Genetic testing for this condition falls under the NHS National Genomic Test Directory (R-code R115), allowing eligible patients in the UK to access testing. A clinical geneticist or genetic counsellor can help arrange appropriate testing and interpret the results.
Management & lifestyle
Management of multiple cutaneous/mucosal venous malformation is focused on alleviating symptoms and addressing complications, as there is currently no cure. The specific approach will depend on the size, location, and symptoms of the malformations. Regular monitoring for new or enlarging lesions, particularly in critical areas, is often recommended.
Treatment options may include sclerotherapy, where a solution is injected into the malformation to cause it to shrink or scar, or surgical removal for symptomatic or disfiguring lesions. Laser therapy may also be considered for some superficial lesions. Pain management and monitoring for internal bleeding, especially from gastrointestinal lesions, are also important aspects of care. Individuals affected by VMCM should be managed by a multidisciplinary team, typically coordinated through a specialist centre, to ensure comprehensive care and access to appropriate interventions. Genetic counsellors can provide support and information about the inheritance pattern and family planning.
UK care pathway
In the UK, individuals suspected of having multiple cutaneous/mucosal venous malformation are typically referred to a clinical genetics service. This service can provide expert assessment, discuss the implications of the condition, and coordinate genetic testing as per the NHS National Genomic Test Directory. For this condition, the relevant R-code for genetic testing is R115. A genetic counsellor will also be available to offer support and information about inheritance, testing for family members, and navigating care pathways within the NHS. Multidisciplinary teams in specialist centres often manage the ongoing care for vascular malformations.
Frequently asked questions
Are the venous malformations cancerous?
No, the venous malformations in this condition are benign, meaning they are not cancerous. However, they can still cause symptoms and complications depending on their size and location.
Will the venous malformations get bigger over time?
The venous malformations are present from birth, but they can increase in size, particularly during childhood, adolescence, and periods of hormonal change like puberty or pregnancy. They typically do not disappear on their own.
Can I pass this condition on to my children?
Yes, if you have multiple cutaneous/mucosal venous malformation, there is a 50% chance with each pregnancy that your child will inherit the altered gene and develop the condition, as it is inherited in an autosomal dominant pattern. A genetic counsellor can provide detailed information and support.
Is there a cure for multiple cutaneous/mucosal venous malformation?
Currently, there is no cure for this condition. Management focuses on treating symptoms and complications, which may include procedures like sclerotherapy, surgical removal, or laser therapy, depending on the individual's specific needs.
What kind of doctor should I see for this condition?
It is generally recommended to be seen by a clinical genetics service for diagnosis and ongoing management advice. You may also be referred to specialists like dermatologists, interventional radiologists, or surgeons, depending on the location and nature of your venous malformations.