Genetics of Klippel-Trenaunay-Weber Syndrome 

Numerous rare congenital defects of skin, blood vessels, and underlying soft tissue are noted. Klippel-Trenaunay syndrome (KTS) is defined by the presence of a combined vascular malformation of the capillaries, veins, and lymphatics, congenital venous abnormalities, and limb hypertrophy.

Parkes Weber syndrome (PWS) is similar except that an arteriovenous malformation (AVM) occurs in association with a cutaneous capillary malformation and skeletal or soft tissue hypertrophy. Sturge-Weber syndrome is defined by the presence of a meningeal angioma, cutaneous capillary malformation of the face, and glaucoma; this is often accompanied by hemiparesis and hemiatrophy contralateral to the meningeal angioma. Although each of these syndromes is distinct, overlap does rarely occur. This article focuses on Klippel-Trenaunay syndrome and Parkes Weber syndrome.

Isolated reports of cases of limb hypertrophy were published in the 19th century, but the combination of a congenital vascular nevus of an extremity, venous varices on the affected side, and limb hypertrophy was not recognized as a consistent and unique syndrome until a 1900 article by Klippel and Trenaunay. A few years later, Frederick Parkes Weber published a report of similar patients in whom both arteries and veins were enlarged and not just venous abnormalities were present. Patients with limb hypertrophy, cutaneous capillary malformations, and venous and arterial malformations sometimes receive a diagnosis of Klippel-Trenaunay-Weber syndrome.

Klippel-Trenaunay syndrome is characterized by a combined type of vascular malformation of the skin, abnormalities of the venous system and lymphatic system, and limb enlargement due to hypertrophy of soft tissue and bone. The vascular malformation is frequently associated with lymphatic vesicles on the surface of the capillary malformation. The lymphatic vesicles may be present within the vascular malformation. The abnormal venous system may produce protrusions of veins on the surface of the skin called venous flares.

Limb hypertrophy is due to the presence of vascular, venous, and lymphatic abnormalities but also is due to the hypertrophy of soft tissue and bone. The hypertrophy is often asymmetric and often involves the digits. Ninety-five percent of cases involve the lower extremity. Because the vascular abnormalities in Klippel-Trenaunay syndrome are not associated with arterial malformations, flow through the malformations is slow. The combination of low flow vascular abnormalities and lymphatic involvement makes the skin lesions appear bluish or purplish.

In contrast, in Parkes Weber syndrome is characterized by the presence of arteriovenous fistulas. Flow through the cutaneous malformations is fast, and the color is pink. Cardiac hypertrophy or high-output congestive heart failure occurs.

Frequency

United States

• Klippel-Trenaunay syndrome and Parkes Weber syndrome are rare sporadic conditions with no racial or geographic predisposition.

Mortality/Morbidity

• Klippel-Trenaunay syndrome and Parkes Weber syndrome have a mortality rate of 1%.
• All patients have significant morbidity.

  • Hypertrophy of the extremities or digits can be extreme, requiring amputation.
  • Lymphatic involvement with lymph vesicles may lead to poor wound healing.
  • Although superficial vein abnormalities are common, the deep vein can also be involved with thrombosis.
  • Pulmonary embolism may occur in 10% of patients, particularly after surgery.
  • Pain may also be a feature of Klippel-Trenaunay syndrome.
  • One half of patients can be treated solely using medical means.

Race

• No racial predilection is noted.

Sex

• No sex predilection is observed.

Age

• The cutaneous vascular malformation is apparent at birth.
• The venous varicosities and limb hypertrophy may not be apparent initially.
• The average age of presentation of children to a medical center is 4 years.