eMedicine Specialties > Dermatology > Diseases of the Vessels

Klippel-Trenaunay-Weber Syndrome

Author: Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
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Updated: Jun 2, 2009

Introduction

Background

Klippel-Trenaunay syndrome is characterized by a triad of port-wine stain, varicose veins, and bony and soft tissue hypertrophy involving an extremity.

In 1900, noted French physicians Klippel and Trenaunay first described a syndrome in 2 patients presenting with a port-wine stain and varicosities of an extremity associated with hypertrophy of the affected limb's bony and soft tissue. They termed the syndrome "naevus vasculosus osteohypertrophicus." In 1907, Parkes Weber, unaware of Klippel and Trenaunay's report, described a patient with the 3 aforementioned symptoms as well as an arteriovenous malformation of the affected extremity. He termed the process hemangiectatic hypertrophy.

Today, conflicting opinion exists in the literature as whether to separately designate the original triad as Klippel-Trenaunay syndrome and the triad with the addition of arteriovenous malformation as Parkes Weber syndrome. Making the distinction is probably wise given the increased morbidity associated with arteriovenous malformations. For this discussion, the 2 types are considered together.

Pathophysiology

The exact cause of Klippel-Trenaunay-Weber syndrome (KTWS) remains to be elucidated, although several theories exist. Bliznak and Staple suggested intrauterine damage to the sympathetic ganglia or intermediolateral tract leading to dilated microscopic arteriovenous anastomoses as the cause.¹ Servelle believes that deep vein abnormalities, with resultant obstruction of venous flow, lead to venous hypertension, the development of varices, and limb hypertrophy.² Baskerville et al contend that a mesodermal defect during fetal development causes maintenance of microscopic arteriovenous communications.³ Finally, McGrory and Amadio believe that an underlying mixed mesodermal and ectodermal dysplasia is likely responsible for the development of KTWS.⁴

Most cases are sporadic, although a few cases in the literature report an autosomal dominant pattern of inheritance.⁵ A case report of KTWS in a monozygotic twin with an unaffected twin advances the theory of a paradominant inheritance pattern.⁶ This theory suggests that KTWS is produced by a single gene defect lethal in individuals who are homozygous for this gene. Heterozygotes carry the gene but are unaffected. The disease manifests in individuals who demonstrate loss of heterozygosity from a somatic mutation during embryogenesis. In these individuals, only the skin region harboring this cell population demonstrates the KTWS mutation.

The association between the angiogenic factor gene AGGF1 and KTS appears to be significant.⁷ Common AGGF1 variants may confer risk of KTWS.

Kihiczak et al report that KTWS may result from a pathogenic gene for vascular and tissue overgrowth.⁸

Race

No racial predilection is documented.

Sex

KTWS affects females and males equally.

Age

KTWS presents at birth or during early infancy or childhood.

Clinical

History

• Klippel-Trenaunay-Weber syndrome (KTWS) generally affects a single extremity, although cases of multiple affected limbs have been reported. The leg is the most common site followed by the arms, the trunk, and rarely the head and the neck. One report describes only upper limb involvement.⁹
• Most patients demonstrate all 3 signs of the clinical syndrome: port-wine stain, varicose veins, and bony and soft tissue hypertrophies.
• In a series of 252 patients at the Mayo Clinic, 63% of patients had all 3 features and 37% had 2 of the 3 features. Port-wine stain was seen in 98% of patients, varicosities or venous malformations in 72%, and limb hypertrophy in 67%. Atypical veins, including lateral veins and persistent sciatic vein, were present in 72% of patients. Finally, deep venous abnormalities included aneurysmal dilation, hypoplasia, aplasia, and absent or incompetent valves.

Physical

• The capillary hemangioma or port-wine stain usually presents first.
  • This hemangioma has a distinct, linear border that respects the midline. Hemangioma is often noted on the lateral aspect of the limb.
  • It is typically of the nevus flammeus type, but cavernous hemangiomas or lymphangiomas may also occur. Nevus flammeus is a salmon pink patch, sometimes with a verrucous quality, which evolves to a deep purple color with time. Unlike strawberry hemangiomas, the port-wine stain hemangioma possesses neither a proliferative nor a regressing phase.
  • Hemangioma depth is variable. It may be limited to the skin or extend deeper to subcutaneous tissue, including muscle and bone. Visceral organs, such as the pleura, the spleen, the liver, the bladder, and the colon may also be affected. Visceral organ involvement portends greater morbidity secondary to internal hemorrhage that may manifest as hematuria or hematochezia.
  • If large enough, cutaneous hemangiomas may sequester platelets, leading to possible Kasabach-Merritt syndrome, a type of consumptive coagulopathy. The hemangioma often overlies the vascular malformation.
• Varicose veins in KTWS are congenital.
  • The Klippel-Trenaunay vein is a large, lateral, superficial vein sometimes seen at birth. This vein begins in the foot or the lower leg and travels proximally until it enters the thigh or the gluteal area. Otherwise, varicosities may not be clinically evident until the child begins to ambulate.
  • Varicosities may be extensive, though they often spare the saphenous distribution. They are seen below the knee, laterally above the knee, and occasionally in the pelvic region. Varicosities may affect the superficial, deep, and perforating venous systems.
  • Surgical exploration has demonstrated atresia and agenesis of deep veins, compression due to fibrous bands, aberrant arteries, abnormal muscles, or venous sheaths.
  • Rarely, varicosities have been found in the bladder, the colon, and the pulmonary vessels.
  • Varicosities may remain stable in size or gradually expand. Pain and lymphedema are commonly reported. These symptoms may worsen during pregnancy.
• Arteriovenous fistulas, the feature that distinguishes Klippel-Trenaunay syndrome from Parkes-Weber syndrome, are rarely found in the affected extremity.
  • If present, they can occasionally be palpated as a pulsatile mass, thrill, or bruit on physical examination.
  • Hyperthermia and a positive Branham sign (bradycardia with the application of compression on an artery proximal to the malformation) are also indicators of an arteriovenous malformation.
• Bony and soft tissue hypertrophies are the third sign of KTWS.
  • Limb hypertrophy can be secondary to increased length (bony involvement) and/or increased girth (soft tissue involvement). Hypertrophy may be appreciated at birth. It usually progresses during the first years of life. A greater degree of hypertrophy may be seen in patients with coexisting arteriovenous malformation. Although lymphedema is also seen in patients, true hypertrophy of the affected soft tissues is present.
  • Limb discrepancies of as much as 12 cm have been reported.
  • Occasionally, the involved limb may be atrophied rather than hypertrophied.
• Other features include lymphatic obstruction, spina bifida, hypospadias, polydactyly, syndactyly, oligodactyly, hyperhidrosis, hypertrichosis, paresthesia, decalcification of involved bones, chronic venous insufficiency, stasis dermatitis, poor wound healing, ulceration, thrombosis, angiosarcoma, and emboli.^10,11

Causes

See Pathophysiology.

• Search for CME/CE on This Topic »

• Klippel-Trenaunay-Weber Syndrome (Pediatrics: Genetics and Metabolic Disease)
• Arterial Vascular Malformations Including Hemangiomas and Lymphangiomas (Pediatrics: Surgery)
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