Klippel–Trénaunay syndrome

Overview

Klippel–Trénaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of symptoms: port-wine stain (capillary malformation), varicose veins or venous malformations, and hypertrophy (overgrowth) of bones and soft tissues, usually affecting one limb. The condition is present at birth and typically affects the lower extremities, although it can also involve the upper limbs or trunk. KTS is a lifelong condition that varies widely in severity, ranging from mild cosmetic concerns to significant functional impairments and medical complications.

Causes

The exact cause of Klippel–Trénaunay syndrome is not fully understood, but it is believed to result from somatic (non-inherited) mutations in the PIK3CA gene. This gene is involved in cell growth and development. Mutations in PIK3CA lead to abnormal development of blood vessels, lymphatic vessels, and surrounding tissues. The condition is not inherited and typically occurs sporadically. KTS is considered part of the PIK3CA-related overgrowth spectrum (PROS) disorders.

Symptoms

The classic triad of symptoms seen in Klippel–Trénaunay syndrome includes:

• Port-wine stain: A red or purplish vascular birthmark present from birth, usually affecting the affected limb

• Varicose veins: Abnormally enlarged veins that may be visible at birth or develop later in childhood

• Limb overgrowth: Excessive growth of bones and soft tissues, leading to limb length discrepancy and asymmetry

Additional signs and complications may include:

• Lymphatic malformations causing swelling or lymphedema

• Skin ulceration or bleeding from vascular malformations

• Increased risk of blood clots (deep vein thrombosis)

• Functional limitations due to limb size and discomfort

Diagnosis

Diagnosis of Klippel–Trénaunay syndrome is based on clinical evaluation and imaging studies. Key diagnostic steps include:

• Physical examination to assess for the presence of the triad (port-wine stain, varicose veins, and limb overgrowth)

• Ultrasound to evaluate blood flow and detect venous or lymphatic malformations

• MRI or CT scans to assess the extent of tissue and vascular involvement

• Genetic testing for PIK3CA mutations (if available and indicated)

• Monitoring for potential complications, such as clotting disorders or bleeding

Treatment

There is no cure for Klippel–Trénaunay syndrome, and treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach is often required. Treatment options include:

• Compression therapy: Use of compression garments to reduce swelling and improve blood flow

• Pain management: Medications or physical therapy to address discomfort and improve mobility

• Laser therapy: To lighten or reduce the appearance of port-wine stains

• Sclerotherapy: Injection of chemicals into abnormal veins to close them

• Surgical interventions: For varicose veins, limb length discrepancy, or severe vascular malformations

• Monitoring and treatment of complications: Including ulcers, bleeding, or thrombosis

Prognosis

The prognosis for individuals with Klippel–Trénaunay syndrome varies depending on the severity of the condition and the presence of complications. Many individuals with mild forms live relatively normal lives with appropriate management. However, those with more severe cases may experience chronic pain, mobility issues, and increased risk of complications such as deep vein thrombosis or bleeding. With early diagnosis, regular monitoring, and multidisciplinary care, quality of life can be significantly improved, and serious complications can often be prevented or effectively managed.