Introduction

Klippel-Trenaunay Syndrome (KTS) is a rare disorder that affects the normal development of blood vessels and lymph vessels. KTS is a congenital disorder, meaning that it is present from birth. The three main features of KTS are: a port-wine stain birthmark with a pink to reddish-purple discolouration, abnormal formation of veins and lymphatic vessels, and overgrowth of soft tissues and bones.¹ KTS predominantly affects the lower limbs (i.e. the legs) on either side of the body.¹

People who have KTS often have abnormalities in their lymphatic system, but not always.¹ The lymphatic system is a network of vessels that circulates a watery fluid called lymph throughout the body.² The main functions of the lymphatic system are maintaining balanced fluid levels in the body, assisting the body in absorbing fats, and protecting against infection as part of the immune system.³ People with KTS may have lymphatic malformation, meaning they have excess or unusual lymphatic vessels that don’t function normally. Lymphatic malformations in KTS consist of a buildup of lymph in body tissues, leading to swelling and the formation of cysts containing lymph.¹

Because there is no cure for Klippel-Trenaunay Syndrome, it is important to educate oneself about the causes and symptoms of KTS to better manage life with the condition.¹ In this article, we will explore the causes and symptoms of lymphatic issues in KTS.

Basics of the lymphatic system

What is lymph? 

Lymph (pronounced ‘limf’) is the fluid circulating throughout the lymphatic system.² The purpose of the lymph is to collect excess fluid from tissues in the body and return it to the bloodstream. This excess fluid comes from plasma, the liquid portion of your blood, when it flows out of tiny blood vessels called capillaries into nearby tissues. The tissues will absorb the nutrients from the plasma and leave behind waste. The plasma will pick up the waste and return to the bloodstream by flowing through the capillary walls. The excess plasma in your tissues that does not return to the bloodstream this way is picked up by lymphatic capillaries as lymph. From there, the lymphatic system transports lymph through larger tubes called lymphatic vessels until the lymph returns to the bloodstream through two collecting ducts in the upper chest that empty into the subclavian veins.³

Components of the lymphatic system

The lymphatic system is made up of multiple components, including organs and lymphatic vessels. The organs in the lymphatic system are the bone marrow, thymus, lymph nodes, spleen and mucosa-associated lymphoid tissue (MALT). Other parts of the lymphatic system include lymph, lymphatic vessels, collecting ducts, tonsils, and adenoids.³

The lymphatic system includes a number of organs and structures that are also part of the immune system. The bone marrow is responsible for producing blood cells: red blood cells, white blood cells, and platelets. White blood cells are immune cells that defend the body against infections. The thymus plays an important role in the maturation of immune cells called T-cells. Lymph nodes filter the lymph to remove damaged or diseased cells; they also house immune cells that will get rid of bacteria, viruses, and other infectious agents in the lymph. The spleen filters blood and removes cellular debris.³

Function of the lymphatic system

The lymphatic system is part of the body’s immune system. Aside from protecting the body from infection, the lymphatic system ensures the body has balanced fluid levels and helps the body absorb nutrients, including fats and fat-soluble vitamins. The lymphatic system also filters and removes debris from dead cells within the lymph. 

What is Klippel-Trenaunay Syndrome (KTS)?

Klippel-Trenaunay Syndrome affects the formation of blood and lymphatic vessels. KTS is also known as capillary-lymphatic-venous malformation (CLVM) because it describes the abnormal formation or changes of capillaries, lymphatic vessels, and veins.¹ KTS was previously known as Klippel-Trenaunay-Weber Syndrome, which included the diagnosis of arteriovenous malformation, a condition where abnormal tangles form in blood vessels where veins and arteries meet. A similar but separate condition called Parkes-Weber syndrome now encompasses arteriovenous malformation.¹

The vessels that KTS impacts are:⁴

• Capillaries – small blood vessels connecting arteries and veins
• Lymphatic vessels – vessels that transport lymph
• Veins – blood vessels carrying blood to the heart 

The primary features of KTS are:

• Port-wine stains – birthmarks that result from capillary malformations^4,5
• Venous malformations – can lead to varicose veins in the calf or thigh area and increase the risk of deep vein thrombosis (DVT)^4,5
• Lymphatic malformations – can lead to leakage of lymph, causing swelling and pelvic and intestinal issues⁴
• Soft tissue or bone overgrowth (hypertrophy) – can result in larger lower limbs (e.g. legs), often only affecting one leg^4,5

Cause of KTS

Mutations or changes in the gene PIK3CA are the most common link to having KTS. These mutations are not inherited from your parents but occur during foetal development.^1,6,7 People can develop KTS without a genetic mutation in PIK3CA. Researchers believe mutations in other genes may cause KTS as well.⁸ 

Lymphatic abnormalities in KTS

Lymphatic abnormalities often occur in KTS and can contribute to lymphoedema, or swelling from lymphatic fluid buildup, usually in one of the legs.⁹ Although the legs are the most commonly affected area in KTS, the arms can also be affected. KTS in the torso or neck is very rare.¹⁰

Lymphatic malformations, where lymphatic vessels are not formed properly, are common features of KTS.⁹ Skin stains are discoloured areas of the skin caused by defects in blood vessels or lymph vessels. In KTS with lymphatic problems, skin stains like port-wine stains can appear dark red or purple and have sharp borders. This pattern of skin stain is called geographic. In segmental stains, skin stains are lighter in colour and appear blotchy. Segmented skin stains do not result from lymphatic vessel deformities.¹¹

An infant who has KTS may have an enlarged arm or leg. Enlarged veins or lymph vessels can cause an abnormally large upper or lower limb and lead to the overgrowth of bones and soft tissue that contribute even more to the enlargement of that limb.¹¹

Symptoms of KTS

We have previously gone over the main features of KTS in other sections. The main symptoms of KTS are port-wine stains; vein and lymphatic vessel malformation; and overgrowth of an arm or a leg, bones or soft tissue. Other signs related to these main symptoms include:

• Visible swelling, usually of the upper or lower limbs (arm or leg)⁹
• Skin changes (thickening, discolouration)¹¹
• Recurrent infections (e.g., cellulitis in the skin)^11,12,13
• Pain or heaviness in affected limbs^11,14
• Leakage of lymph fluid in severe cases^11,14

Bacterial infection of the skin, or cellulitis, is a complication found in people with KTS caused by leakage of lymphatic vessels and bleeding.^12,13 This is due to the breakdown of the skin surface, which allows bacteria to enter the skin.¹⁴

Lymphoedema arises from lymphatic abnormalities in KTS. Lymphoedema can lead to sustained fluid buildup, impaired immunity, fat accumulation and fibrosis.^14,15,16

Impact and management

Globally, an estimated 1 in 100,000 people have Klippel-Trenaunay Syndrome. KTS affects both sexes equally and can occur in people of any ethnicity.⁵ Because there is no cure for KTS, doctors treat the condition by managing its symptoms. Treatment for KTS depends on the severity of the condition and complications.¹¹ 

People with KTS should be informed that the condition is progressive, meaning it can change or worsen over time. Parents of children diagnosed with KTS should be educated on complications and management, particularly when it comes to monitoring the length of affected limbs in their child.¹ Diagnosis of KTS is usually done by pediatric healthcare providers because KTS symptoms are often observed after birth through childhood. Other specialised healthcare professionals, such as dermatologists (skin doctors), haematologists (blood doctors), orthopaedists (muscle and skeleton doctors), and vascular surgeons, also provide care to patients with KTS depending on their symptoms and the seriousness of their disease. Multidisciplinary medical care is the best approach for managing KTS. Surgery is needed in only a few instances and should be tailored to the individual patient’s needs.¹

People with KTS should be educated on skin care to prevent bacterial infection of the skin.¹ KTS can result in physical discomfort or pain in affected limbs.⁴ If someone with KTS has enlarged limbs, this can provide challenges in movement. Surgeries are available to correct vein problems or reduce the size of overgrown limbs, but patients should be aware that they may need anti-thrombotic prophylaxis, medication to prevent blood clots, 2 weeks before surgery.¹

Summary

Klippel-Trenaunay Syndrome (KTS) is a rare congenital condition that causes problems in the formation of blood vessels and lymph vessels. The key features of KTS are port-wine stains, vein and lymphatic vessel abnormalities, and overgrown limbs, soft tissues, or bones. The main cause of KTS is a mutation or change in the gene PIK3CA that occurs after conception. Lymphatic complications are common in people with KTS and can cause lymphatic swelling (lymphoedema) in tissues and affected limbs, skin discolouration, bacterial skin infections, pain, and even leakage of lymph fluid. Lymphoedema can cause fluid buildup in the limbs and impair immune responses. Diagnosis and multidisciplinary medical care are important for managing life with KTS and ensuring better outcomes in the treatment of symptoms.