Klippel-Trenaunay Syndrome Patients Research Articles

Total hip arthroplasty in Klippel–Trenaunay syndrome

Klippel-Trenaunay syndrome patients often suffer degenerative joint disease at an early age. Performing arthroplasty in these patients is particularly difficult for a number of reasons. In this case report, we describe the second reported case of total hip replacement in Klippel-Trenaunay syndrome, using novel techniques to surmount the problems faced in this challenging condition.

Identification of Association of Common AGGF1 Variants with Susceptibility for Klippel‐Trenaunay Syndrome Using the Structure Association Program

Klippel-Trenaunay syndrome (KTS) is a severe congenital disorder characterized by capillary malformations, venous malformations or varicose veins, and hypertrophy of the affected tissues. The angiogenic factor gene AGGF1 was previously identified as a candidate susceptibility gene for KTS, but further genetic studies are needed to firmly establish the genetic relationship between AGGF1 and KTS. We analyzed HapMap data and identified two tagSNPs, rs13155212 and rs7704267 that capture information for all common variants in AGGF1. The two SNPs were genotyped in 173 Caucasian KTS patients and 477 Caucasian non-KTS controls, and both significantly associated with susceptibility for KTS (P= 0.004 and 0.013, respectively). Permutation testing also showed a significant empirical P value for the association (empirical P= 0.006 and 0.015, respectively). To control for potential confounding due to population stratification, the population structure for both cases and controls was characterized by genotyping of 38 ancestry-informative markers (AIMs) and the STRUCTURE program. The association between the AGGF1 SNPs and KTS remained significant after multivariate analysis by incorporating the inferred cluster scores as a covariate or after removal of outlier individuals identified by STRUCTURE. These results suggest that common AGGF1 variants confer risk of KTS.

Genetic aspects of the Klippel-Trenaunay syndrome.

An extensive search for a genetic pattern in Klippel-Trenaunay syndrome (KTS) revealed two other cases of KTS in the families of two of the 86 patients with this vascular syndrome who were questioned. Patients with KTS also had family members with other malformations: e.g. hemihypertrophy in one family, and a prevalence of 7/400 of naevi flammei in first-degree relatives of KTS patients was observed. We suggest that KTS can be inherited in a multifactorial way and a range of vascular malformations can be observed in the family members of patients with this syndrome.

Syndrome de Klippel-Trenaunay et déficit en antithrombine III: À propos d’une observation

Klippel–Trenaunay syndrome (KTS) is a rare phakomatosis characterized by cutaneous hemangiomata, venous varicosities and bone and soft tissue hypertrophy also of the affected limb. Central nervous system involvement is rare, arising from a malformation or from coagulation disorders. We report the case of a patient presenting a KTS with stroke. The biological assessment revealed antithrombin III deficiency. Although rare, antithrombin III deficiency should be kept in mind in KTS patients with neurological involvement.

Endovascular radiofrequency ablation: A novel treatment of venous insufficiency in Klippel-Trenaunay patients

Klippel-Trenaunay Syndrome (KTS) is an uncommon congenital disorder of uncertain etiology that comprises the clinical triad of varicose veins, port wine stain, and bony or soft-tissue hypertrophy. The literature suggests that the deep venous system is often under-developed. We propose that duplex venous ultrasound can effectively demonstrate patent deep venous systems in KTS patients with mild to moderate disease, and that endovascular radiofrequency ablation can be utilized in a safe and appropriate therapeutic manner. A single center retrospective review of three patients with KTS treated with endovascular radiofrequency ablation of the KT veins and/or great saphenous veins was conducted. Preoperatively, patients underwent both venography and were studied with color flow duplex ultrasound system iU22 with a 7-5 MHz linear array probe (Philips Medical Systems, NA, Bothell, Wash). The anomalous KT veins, great saphenous and saphenous tributaries, and associated incompetent perforators were ablated with radiofrequency catheters (VNUS Medical Technologies, Inc, San Jose, Calif). All the radiofrequency ablations were complimented by ultrasound guided sclerotherapy of the varicose tributaries and when evident, incompetent perforator veins. The diagnostic series of duplex ultrasounds performed on our KTS patients has demonstrated contiguous deep venous systems in the effected extremity and effectively recognized the associated anomalous superficial venous systems. Our treatment resulted in successful occlusion of the incompetent veins in all three patients. The three patients, females aged 39, 19, and 16, presented with port wine stains and many years of leg-swelling and varicose veins that were recalcitrant to conservative treatment measures, including compression stockings and pulsed-dye laser therapy. Venography initially revealed poorly developed deep venous systems. However, venous ultrasound demonstrated patent and competent deep venous systems in all of the affected limbs. Radiofrequency ablations were performed to manage the sequella of venous insufficiency. At short-term follow-up, all patients demonstrated markedly decreased leg pain, edema, and varicose vein bulging. Three KTS patients were successfully treated with radiofrequency ablation of the incompetent great saphenous and/or anomalous superficial veins. Although the deep veins were poorly visualized on venography, they were clearly demonstrated with duplex ultrasound and functioned adequately once the incompetent superficial veins were ablated.

Wilms tumor screening is unnecessary in Klippel-Trenaunay syndrome.

Children with hemihypertrophy are screened for Wilms tumor, because this condition is a risk factor for developing the neoplasm. Patients with Klippel-Trenaunay syndrome (KTS) are often considered potential candidates for Wilms tumor, because they have unilateral overgrowth of the lower limb. In our experience, however, an association between KTS and Wilms tumor has not been observed. To determine whether KTS and Wilms tumor are associated, we reviewed our institutional experience for patients with both diagnoses and searched the Klippel-Trenaunay literature for patients with Wilms tumor. The National Wilms Tumor Study Group database also was studied to identify patients with KTS. Two-sided exact binomial tests were used to evaluate whether patients with 1 condition had an increased risk for the other. Ninety-five percent confidence intervals for these 2 risks were compared with the general population risks of Wilms tumor (1 in 10 000) and KTS (1 in 47 313). None of the 115 patients with KTS followed at our institution developed Wilms tumor. One case of Wilms tumor has been reported in 1363 patients with KTS in the literature, giving a confidence interval of (1/57 377) and (1/267). None of the 8614 patients in the National Wilms Tumor Study Group database had KTS, giving a confidence interval of (0, 1/2336). Because the risks of KTS and Wilms tumor in the population fall within these confidence intervals, one cannot conclude that the risks of KTS among Wilms tumor patients or Wilms tumor among KTS patients are any different from the corresponding risks in the general population. Patients with KTS are not at increased risk for developing Wilms tumor and thus should not undergo routine ultrasonographic screening.

Identification of an angiogenic factor that when mutated causes susceptibility to Klippel-Trenaunay syndrome.

Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). One mutation is chromosomal translocation t(5;11), which increases VG5Q transcription. The second is mutation E133K identified in five KTS patients, but not in 200 matched controls. VG5Q protein acts as a potent angiogenic factor in promoting angiogenesis, and suppression of VG5Q expression inhibits vessel formation. E133K is a functional mutation that substantially enhances the angiogenic effect of VG5Q. VG5Q shows strong expression in blood vessels and is secreted as vessel formation is initiated. VG5Q can bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. We also demonstrate a direct interaction of VG5Q with another secreted angiogenic factor, TWEAK (also known as TNFSF12). These results define VG5Q as an angiogenic factor, establish VG5Q as a susceptibility gene for KTS, and show that increased angiogenesis is a molecular pathogenic mechanism of KTS.

Klippel-Trenaunay syndrome: A rare cause of severe headache

Klippel-Trenaunay Syndrome (KTS) is a rare condition characterized by the triad of capillary malformations (port-wine stains), venous malformations, and soft tissue and/or bony hypertrophy. Many patients with KTS have pain of the affected area of the body. We report a unique KTS patient with multiple intraosseous calvarial venous malformations producing severe chronic headaches.