Syndromic Vascular Malformations

Syndromic vascular malformations are rare conditions present from birth that affect your blood vessels and lymphatic system. Unlike simple birthmarks or isolated vascular problems, these syndromes involve abnormal blood or lymphatic vessels along with other features such as overgrowth of a limb, skin changes, or bone abnormalities.

These conditions are not cancerous. Instead, they are errors in how your blood vessels developed before you were born.

The malformations are present at birth, though symptoms may not appear until infancy, childhood, or even adulthood.

• Common types of syndromic vascular malformations
  
  • PIK3CA-Related Overgrowth Spectrum (PROS): A group of genetic disorders with overgrowth of various body parts due to changes in the PIK3CA gene. Overgrowth may stop in childhood or continue into adulthood. This spectrum includes:
    
    • Klippel-Trenaunay Syndrome (KTS): This condition typically involves three main features – a port-wine stain (pink or red birthmark), enlarged veins, and overgrowth of one limb (usually a leg). The blood flow in these malformations is slow.
    • CLOVES Syndrome: This stands for Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, and Scoliosis/Skeletal anomalies. It involves fatty tissue overgrowth, vascular malformations, skin changes, and bone/spine problems.
      
  • Parkes Weber Syndrome (PWS): Similar to KTS but with abnormal connections between arteries and veins (arteriovenous malformations or AVMs) that cause fast blood flow. Treatment differs between the two conditions.
    
  • Blue Rubber Bleb Nevus Syndrome (BRBNS): Characterised by blue or purple skin lesions that look like rubber and can also occur in the digestive tract, potentially causing bleeding.
    
    
• What causes these conditions?
  Most syndromic vascular malformations are caused by genetic changes (mutations) that occur randomly during development, that are not inherited from parents. These mutations affect specific pathways in cells that control growth and blood vessel formation, particularly the PI3K-AKT-mTOR and RAS-MAPK pathways. Understanding the genetic cause has led to new treatment options that target these specific pathways.

• How do syndromic vascular malformations present?
  Symptoms vary widely depending on the specific syndrome and which parts of the body are affected:
  
  • Visible skin changes such as port-wine stains (capillary malformations), blue or purple spots, or other birthmarks
  • Swelling or enlargement (hypertrophy) of a limb or body part
  • Pain, especially with activity or changes in temperature
  • Bleeding from skin lesions or internal organs
  • Difficulty with movement/walking if bones or joints are affected
  • Functional problems such as breathing, swallowing, vision difficulties
  • Blood clots or risk of blood clots in the lungs (pulmonary embolism)

  The severity can range from mild cosmetic concerns to serious, life-threatening complications.

• How are these conditions diagnosed?
  Diagnosis typically involves:
  
  • Physical examination by specialists familiar with vascular anomalies
    
  • Imaging studies such as ultrasound, MRI, or CT scans to assess the extent and type of malformation
    
    • Sometimes angiography (special X-rays of blood vessels) may be performed to determine blood flow patterns
      
  • Genetic testing may be performed on affected tissue to identify specific mutations, which can help guide treatment
     
• What treatment options are available?
  Treatment is individualised based on your specific condition, symptoms, and how the malformation affects your daily life. Our multidisciplinary vascular anomalies team will work together to help manage your condition.
  
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  • Conservative management: If the malformation is not causing significant problems, careful monitoring may be all that's needed.
  • Medications: New targeted therapies help improve symptoms and quality of life. These include:
    
    • Sirolimus (an mTOR inhibitor): for most slow-flow vascular malformations especially lymphatic malformations and some venous malformations.
      
    • Alpelisib (a PIK3CA inhibitor): for conditions caused by PIK3CA mutations including lymphatic and venous malformations and PROS.
      
    • Trametinib (a MEK inhibitor): may be used in conditions caused by changes in genes in the MAP2K pathway such as AVMs and some syndromic complex lymphatic anomalies.
      
    • Thalidomide (an anti-angiogenic medication): blocks growth of abnormal new blood vessels and reduces bleeding in AVMs.
      
    • Pain medications and anti-inflammatory drugs may be used for symptom control.
  • Sclerotherapy: A procedure where medication is injected directly into the malformation to shrink it. This is commonly used for venous and lymphatic malformations.
  • Embolisation: A procedure to block abnormal blood vessels, often used for arteriovenous malformations.
    
  • Surgery: May be recommended for malformations causing significant problems, though complete removal is not always possible.
    
  • Combination approaches: Many patients benefit from a combination of treatments, such as embolisation followed by surgery or sclerotherapy combined with medication.
    
  • Regular follow-up with your medical team is essential for monitoring and managing complications.
    
    
• What Is the long-term outlook for syndromic vascular malformations?
  The prognosis varies significantly depending on the specific syndrome and its severity. But it is important points to understand that:
  
  • These conditions are lifelong and currently have no cure, though symptoms can often be well-managed.
    
  • Malformations may grow or change over time, particularly during adolescence or with hormonal changes, such as during pregnancy.
    
  • Some syndromes carry risks of serious complications like blood clots, bleeding, or organ dysfunction.
    
  • New targeted therapies are improving outcomes and quality of life for many patients.

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