Genetics of Klippel-Trenaunay-Weber Syndrome

Updated: Aug 29, 2016
  • Author: Ravi Sunderkrishnan, MD; Chief Editor: Maria Descartes, MD  more...
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Overview

Background

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. See the image below.

Klippel-Trenaunay syndrome in a young person. Note Klippel-Trenaunay syndrome in a young person. Note the port-wine stain extending to the buttocks. These lesions can be associated with venous malformations involving the rectum and bladder.

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 enlarged arteries and veins, rather than 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.

Parkes Weber syndrome (PWS) is closely associated with and similar to Klippel-Trenaunay syndrome, 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. [1]

Although each of these syndromes is distinct, overlap does rarely occur. This article focuses on Klippel-Trenaunay syndrome and Parkes Weber syndrome.

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Pathophysiology

Klippel-Trenaunay syndrome is characterized by a combined type of vascular malformation of the skin, abnormalities of the venous and lymphatic systems, and limb enlargement. Lymphatic vesicles appear on the surface of the capillary malformation; the lymph may also ooze at times. In addition, the abnormal venous system may produce protrusions of veins on the surface of the skin, called venous flares. Varicose veins appear in early childhood, and lateral venous anomalies are seen in 80% of cases.

Limb hypertrophy is due to the presence of vascular, venous, and lymphatic abnormalities but also to the hypertrophy of soft tissue and bone. The hypertrophy is often asymmetrical 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, Parkes Weber syndrome is characterized by the presence of arteriovenous fistulas, and flow through the cutaneous malformations is fast, giving the lesions a pink color. Cardiac hypertrophy or high-output congestive heart failure occurs.

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Epidemiology

Frequency

United States

Klippel-Trenaunay syndrome and Parkes Weber syndrome are rare sporadic conditions with no racial or geographic predisposition. Parkes Weber syndrome is much less common than Klippel-Trenaunay syndrome.

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. [2]  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. A study by Sung et al of 19 patients with Klippel-Trenaunay syndrome found a nearly even sex distribution of nine males and 10 females. [3]

Age

The cutaneous vascular malformation is apparent at birth, but 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.

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