Klippel-Trenaunay-Weber syndrome (KTS) is a rare vascular congenital malformation characterized by the presence of port-wine stains, hypertrophy of bones and soft tissues, and varicose veins. The port-wine stains are purplish discolorations caused by swollen blood vessels. The vascular malformations are present at birth and continue to progress with time. Blood flow through them is sluggish, resulting in ischemia and painful thrombotic events. Bleeding from the rectum, or blood in the urine may also be noticed. The condition is subject to significant morbidity, including bleeding, deep vein thrombosis, embolic complications, and/or limb enlargement, sometimes requiring amputation. The exact cause of KTS is not known. However, many theories have been proposed to explain its etiology. These include theories proposing intrauterine damage to the sympathetic ganglion, deep vein abnormalities, mesodermal defect during fetal development, and mixed mesodermal and ectodermal dysplasia.
In most cases, medical history and clinical examination are enough to diagnose the condition, although work-up may involve non-invasive imaging using Doppler ultrasound, standard radiography, or MRI. Treatment is symptomatic. Compression garments, pneumatic compression pumps, medications for pain management, anticoagulant therapy, and others may all be useful. Surgical intervention is recommended only for significant cosmetic deformity or symptoms of pain, heaviness of legs, bleeding, and/or infectious complications. Of late, endovenous laser therapy of the greater saphenous vein has become popular for the management of varicosities.
Klippel-Trenaunay syndrome is, in most cases, a sporadic disease, although familial cases have also been reported. The familial cases show an autosomal dominant or paradominant mode of inheritance. A heterozygous glu133-to-lys (E133K) non-conservative substitution in the VG5Q (Angiogenic Factor with G-Patch and FHA Domains 1) gene had earlier been implicated in the pathogenesis of the condition. However, a later study showed this to be a non-specific polymorphism. The earliest cytogenetic study on this disease showed a translocation of 5q and 11p, raising the possibility of a mutation at either of these sites. Subsequent cytogenetic studies have implicated a region on chromosome 8q to be involved the pathogenesis of the condition.