7 Key Symptoms of Klippel-Trenaunay Syndrome You Should Know

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder characterized by a triad of features that affect blood vessels, soft tissues, and bones. Named after the two French physicians who first described it in 1900, this condition occurs in approximately 1 in 100,000 live births. The syndrome is present at birth and typically affects one limb, most commonly a leg, though it can involve multiple limbs or other body parts. Understanding the symptoms of Klippel-Trenaunay syndrome is crucial for early diagnosis and proper management of this lifelong condition.

The syndrome results from abnormal development of blood vessels, soft tissues, and bones during fetal development. While the exact cause remains unclear, most cases occur sporadically without a family history. The symptoms can vary significantly in severity from person to person, ranging from mild cosmetic concerns to serious complications affecting mobility and quality of life. Early recognition of these symptoms allows for timely intervention and better outcomes.

1. Port-Wine Stain Birthmarks

One of the most visible and characteristic symptoms of Klippel-Trenaunay syndrome is the presence of port-wine stain birthmarks, medically known as capillary malformations. These distinctive marks appear as flat, pink, red, or purple discolorations on the skin that are present from birth.

The port-wine stains in KTS typically cover a large area of the affected limb and may extend to adjacent areas of the body. Unlike some birthmarks that fade over time, these marks are permanent and may darken or thicken with age. The affected skin area usually feels warm to the touch due to increased blood flow through the abnormal capillaries beneath the surface.

Key characteristics include:

• Usually appear on one side of the body
• Most commonly affect the leg, but can occur on arms, trunk, or face
• Range in color from light pink to deep purple
• May become darker and more raised over time
• Can cause psychological distress due to cosmetic appearance

2. Limb Hypertrophy and Overgrowth

Abnormal limb growth, or hypertrophy, is a hallmark feature of Klippel-Trenaunay syndrome. This symptom involves excessive growth of bones and soft tissues in the affected limb, making it larger than the corresponding limb on the opposite side of the body.

The overgrowth typically affects the entire limb but may be more pronounced in certain areas. It usually involves increased length, circumference, or both. In most cases, the leg is affected, though arms can also show hypertrophy. This discrepancy in limb size becomes more noticeable as the child grows and can lead to significant functional problems.

The overgrowth manifests as:

• Increased bone length causing leg length discrepancy
• Enlarged circumference due to soft tissue swelling
• Increased foot or hand size on the affected side
• Progressive difference that becomes more apparent with age
• Possible involvement of fingers or toes, causing them to be disproportionately large

This size difference can cause problems with walking, balance, and posture. Children may develop an abnormal gait pattern, and adults may experience chronic pain and mobility limitations.

3. Varicose Veins and Venous Malformations

Abnormal development of veins is a core feature of Klippel-Trenaunay syndrome. Patients typically develop extensive varicose veins at an unusually young age, sometimes even visible at birth or during early childhood, which is highly unusual compared to typical varicose veins that develop in adulthood.

These varicose veins are not merely cosmetic issues but represent significant malformations in the venous system. They may involve superficial veins that are visible beneath the skin or deeper veins that affect blood return from the limbs. The venous malformations can be complex and involve multiple types of abnormal vessels.

Venous complications include:

• Bulging, twisted veins visible under the skin
• Swelling that worsens throughout the day or with activity
• Heaviness or aching sensation in the affected limb
• Skin discoloration and texture changes
• Increased risk of blood clots (thrombosis)
• Possible bleeding from superficial veins

The venous malformations can extend into deeper tissues and even involve internal organs in some cases, though this is less common.

4. Lymphatic Abnormalities and Swelling

Many individuals with Klippel-Trenaunay syndrome experience lymphatic system dysfunction, which leads to chronic swelling known as lymphedema. The lymphatic vessels, which normally drain fluid from tissues back into the bloodstream, may be absent, malformed, or insufficient in the affected limb.

Lymphedema in KTS typically affects the same limb as the other symptoms and can range from mild to severe. The swelling is usually persistent and may worsen with heat, prolonged standing, or physical activity. Unlike the swelling caused by venous problems that may improve with elevation, lymphedema tends to be more resistant to simple interventions.

Lymphatic involvement presents as:

• Persistent swelling that may not improve with elevation
• Feeling of heaviness or tightness in the limb
• Decreased flexibility in joints due to swelling
• Thickened or hardened skin texture
• Increased susceptibility to skin infections (cellulitis)
• Fluid-filled blisters (lymphatic vesicles) that may leak clear fluid

The combination of venous and lymphatic problems creates a complex situation that contributes significantly to limb enlargement and discomfort.

5. Pain and Discomfort

Chronic pain is a common and often underestimated symptom of Klippel-Trenaunay syndrome. The pain can arise from multiple sources including the vascular malformations, bone overgrowth, and associated complications. Many patients report that pain significantly impacts their daily activities and quality of life.

The pain associated with KTS varies in character and intensity. It may be constant or intermittent, ranging from mild discomfort to severe, debilitating pain. The affected limb may feel heavy, achy, or burning. Pain often worsens with prolonged standing, walking, or at the end of the day when fluid accumulation is greatest.

Pain characteristics include:

• Aching or throbbing sensation in the affected limb
• Sharp pains associated with nerve involvement
• Burning sensation in areas of vascular malformation
• Joint pain due to biomechanical stress from limb length discrepancy
• Muscle cramps and spasms
• Pain that interferes with sleep and daily activities

The pain may also result from complications such as thrombophlebitis (inflammation of veins with blood clots), skin infections, or orthopedic problems related to uneven limb growth.

6. Skin Changes and Complications

The skin overlying the affected limb in Klippel-Trenaunay syndrome often undergoes various changes beyond the port-wine stain. These skin alterations reflect the underlying vascular and lymphatic abnormalities and can lead to additional complications if not properly managed.

The compromised blood and lymph flow in the affected area makes the skin more vulnerable to breakdown, infection, and poor healing. The skin may appear discolored, with areas of darkening or bronze pigmentation. In severe cases, the skin can develop a thickened, roughened texture resembling orange peel.

Common skin manifestations include:

• Hyperpigmentation or darkening of the skin
• Dry, scaly skin that may crack
• Eczema or dermatitis in affected areas
• Ulcers or wounds that heal slowly
• Bleeding from small vessel malformations near the surface
• Increased warmth in affected areas
• Cellulitis or other bacterial skin infections
• Development of wart-like growths

These skin changes require careful attention and appropriate care to prevent serious complications such as non-healing ulcers or recurrent infections.

7. Orthopedic and Mobility Issues

The limb overgrowth characteristic of Klippel-Trenaunay syndrome inevitably leads to orthopedic complications and mobility challenges. The difference in limb length and size creates biomechanical problems that affect the entire musculoskeletal system, not just the affected limb.

As the affected limb grows disproportionately, patients may develop compensatory changes in posture and gait. One leg being longer or larger than the other forces the body to adapt, often leading to secondary problems in the hips, back, and spine. Children may have difficulty with normal motor development, and adults often experience progressive orthopedic deterioration.

Orthopedic complications include:

• Limb length discrepancy causing uneven gait
• Scoliosis or abnormal spinal curvature
• Hip problems and pelvic tilt
• Knee pain and arthritis from uneven stress
• Foot deformities and altered foot mechanics
• Balance difficulties and increased fall risk
• Reduced range of motion in joints
• Muscle imbalances and weakness
• Early-onset degenerative joint disease

The increased weight and size of the affected limb, combined with potential pain and swelling, can make walking and other physical activities challenging, potentially limiting independence and participation in normal activities.

Main Causes of Klippel-Trenaunay Syndrome

The exact cause of Klippel-Trenaunay syndrome remains incompletely understood, but research has provided important insights into the mechanisms behind this condition. Understanding these causes helps explain why the symptoms develop and why the syndrome manifests so variably among affected individuals.

Genetic Mutations: Recent research has identified mutations in the PIK3CA gene as a cause of some cases of KTS. This gene provides instructions for making a protein that helps regulate cell growth and division. Mutations cause cells to grow and divide abnormally, leading to the vascular and tissue overgrowth seen in the syndrome. These mutations are typically somatic, meaning they occur randomly during early fetal development rather than being inherited from parents.

Sporadic Occurrence: The vast majority of Klippel-Trenaunay syndrome cases occur sporadically without any family history of the condition. This means that the genetic changes happen spontaneously during embryonic development rather than being passed down through generations. Parents of an affected child typically have normal genes and a very low risk of having another child with the condition.

Embryonic Development Errors: The syndrome is believed to result from errors that occur during fetal development, specifically affecting the development of blood vessels, soft tissues, and bones. These errors occur very early in pregnancy, during the formation of the vascular system, which explains why the malformations are present at birth.

Mosaic Pattern: The genetic mutations in KTS typically follow a mosaic pattern, meaning that only some cells in the body carry the mutation while others are normal. This explains why the symptoms usually affect only one limb or one side of the body rather than the entire body symmetrically.

Vascular Development Abnormalities: The core problem in KTS involves abnormal development of the vascular system, including capillaries, veins, and lymphatic vessels. These vessels fail to develop properly, leading to malformations that persist throughout life and may worsen with age.

Prevention

Unfortunately, there are currently no known methods to prevent Klippel-Trenaunay syndrome. Since the condition results from spontaneous genetic mutations that occur during early fetal development, it cannot be prevented through lifestyle changes, medications, or other interventions before or during pregnancy.

However, while the syndrome itself cannot be prevented, many of its complications can be minimized through early detection and appropriate management:

Early Diagnosis and Monitoring: Recognizing the signs of KTS early allows for prompt intervention and monitoring. Regular follow-up with healthcare providers can help detect complications before they become severe.

Preventive Measures for Complications: While the syndrome cannot be prevented, patients can take steps to prevent or minimize complications:

• Wearing compression garments to reduce swelling and support abnormal veins
• Maintaining a healthy weight to reduce stress on the affected limb
• Practicing good skin hygiene to prevent infections
• Avoiding prolonged standing or sitting
• Elevating the affected limb when possible
• Protecting the skin from injury and treating wounds promptly
• Staying physically active within individual limitations

Genetic Counseling: For families with a child diagnosed with KTS, genetic counseling can provide information about recurrence risks and help with family planning decisions. While the recurrence risk is generally very low, counseling can address concerns and provide support.

Prenatal Diagnosis Limitations: KTS is typically not detected before birth through routine prenatal screening. Some severe cases might show limb size differences on detailed ultrasound, but most cases are diagnosed after birth when the characteristic features become apparent.

Frequently Asked Questions

Is Klippel-Trenaunay syndrome hereditary?

In most cases, no. KTS typically occurs sporadically due to random genetic mutations during fetal development. It is rarely inherited from parents, and most affected individuals have no family history of the condition. The risk of passing it to children is generally very low.

Can Klippel-Trenaunay syndrome affect internal organs?

Yes, although less common, KTS can affect internal organs. Vascular malformations may involve the bladder, rectum, spleen, or other organs. Internal involvement can lead to complications such as bleeding or organ dysfunction, making comprehensive medical evaluation important.

Does Klippel-Trenaunay syndrome get worse with age?

The syndrome itself is present from birth, but symptoms often become more pronounced with age. The port-wine stain may darken and thicken, varicose veins typically worsen, and limb overgrowth continues through childhood growth years. Complications such as pain, skin changes, and orthopedic problems may also progress over time.

How is Klippel-Trenaunay syndrome diagnosed?

Diagnosis is primarily clinical, based on the presence of the characteristic triad: port-wine stain, limb overgrowth, and varicose veins. Imaging studies such as ultrasound, MRI, or CT scans help evaluate the extent of vascular malformations and bone abnormalities. Genetic testing may identify PIK3CA mutations in some cases.

Can people with Klippel-Trenaunay syndrome live normal lives?

Many people with KTS can lead relatively normal lives, though they may face challenges related to their symptoms. The severity varies widely among individuals. With appropriate management, supportive care, and monitoring for complications, many affected individuals can participate in regular activities, attend school or work, and maintain good quality of life.

What is the difference between Klippel-Trenaunay syndrome and Parkes Weber syndrome?

While both conditions involve limb overgrowth and vascular malformations, Parkes Weber syndrome specifically includes arteriovenous fistulas (abnormal connections between arteries and veins), which are not present in classic KTS. Parkes Weber syndrome may have more severe complications due to these high-flow vascular connections.

Are there any dietary restrictions for people with KTS?

There are no specific dietary restrictions for KTS itself. However, maintaining a healthy weight is important to reduce stress on the affected limb and joints. Some individuals may need to stay well-hydrated to support circulation and lymphatic function. Those with increased bleeding risk should consult their healthcare provider before taking supplements that affect blood clotting.

Should children with Klippel-Trenaunay syndrome avoid certain activities?

Activity recommendations depend on individual symptoms and severity. Most children can participate in regular activities with some modifications. High-impact activities or contact sports may pose risks of injury or bleeding, especially if significant vascular malformations are present. Consultation with healthcare providers can help determine appropriate activity levels for each individual.

References:

• Mayo Clinic – Klippel-Trenaunay Syndrome
• National Organization for Rare Disorders (NORD) – Klippel-Trenaunay Syndrome
• National Institute of Neurological Disorders and Stroke – Klippel-Trenaunay Syndrome
• StatPearls – Klippel Trenaunay Syndrome
• Boston Children’s Hospital – Klippel-Trenaunay Syndrome