Discussion

The diagnosis of KTS is usually clinical. The initial diagnostic imaging modality of choice is often Doppler US, which allows for visualization of the varicosities as well as appreciation of any concurrent thrombosis or venous insufficiency. The extent of the US findings directly relates to disease severity. Once extensive venous thrombosis is noted in the setting of possible KTS or a therapeutic intervention is considered, CT or MRI is often needed to determine disease extent. Additionally, these imaging modalities can evaluate for other malformations, including spinal cavernous malformations, pulmonary anomalies, and gastrointestinal malformations.¹

KTS is an uncommon pediatric disease characterized by an activating mutation in the PIK3CA gene, resulting in global or focal tissue overgrowth. The disease is a common subtype of PIK3CA-related overgrowth syndromes and has a variable but classic presentation due to the mosaic pattern of gene mutation.¹ KTS is also associated with a triad of cutaneous angiomas, venous and lymphatic abnormalities, and soft-tissue or bony hypertrophy. A diagnosis of KTS requires 2 of these 3 features.^{2, 3} These abnormalities have various clinical consequences, predominantly limb pain, fatigue, and recurrent superficial and deep-vein thrombosis.⁴ On examination, children with KTS have overgrowth of the affected limbs and/or cutaneous malformations on the trunk. Port-wine stains are the most common skin finding, which are cutaneous manifestations of the underlying capillary malformations.

The focus of therapy in refractory KTS is obliteration or removal of the persistent embryonic veins, which are the common cause of signs and symptoms. The 2 vessels that constitute the most problematic veins in the leg are the lateral marginal vein (LMV) and the persistent sciatic vein (PSV).⁵ The LMV is an embryonic vessel that originates on the dorsal side of the foot and eventually contributes to the small saphenous vein and superficial venous system before naturally regressing. The PSV is a deep vein of the posterior thigh considered the major tributary of the developing deep-venous system before regressing. When these vessels persist, they disrupt the physiological growth of normal venous anatomy and often dilate to large diameters, greatly increasing the risk of venous stasis. When severe, this can result in life-threatening complications, including large-volume bleeding, pulmonary emboli, and venous thromboses.² Despite being a common in affected children, the prevalence of these marginal veins is conservatively measured at around 15% to 20%, likely due to the highly variable phenotype of KTS.⁵

When these embryonic veins only cause mild and nondisruptive symptoms, conservative treatment with compression stockings, pain control, and avoidance of injury are the first-line treatment. Traditionally, surgery has been the primary treatment method for severe or refractory cases. The surgical approach depends on disease extent and usually includes vein stripping, stab phlebectomies (whereby the vein is hooked through a small excision, brought outside the skin, and removed), and gross excision.

Surgery has largely been replaced by more minimally invasive techniques, including embolization using coils, vascular plugs and other materials, endovenous laser ablation therapy (EVLT) such as radiofrequency ablation (RFA), and sclerotherapy. These methods occlude abnormal veins and avoid the potential surgical complications of poor wound closure and persistent bleeding, and are first-line therapies for persistent KTS.¹ Other ablative techniques, such as cryoablation, cannot currently deliver therapy to the entire embryonic vessel, which could result in collateralization and incomplete response. The best approach is not yet known.

EVLT can be used to treat persistent embryonic veins, and acts by emitting a wavelength of light that generates photon-induced damage to the vessel wall as well as thermal damage to the surrounding area.⁶ EVLT is generally well-tolerated, with complications including ecchymosis, skin burns, and thrombophlebitis along the ablated vein. Rarely, heat-induced thrombus may occur, which is defined as postprocedural thrombus propagating into deeper vessels cephalad to the treated area.⁷ RFA may cause tissue necrosis in a localized area by agitating adjacent molecules and producing high temperatures.⁷ The complications of RFA are the same as those of EVLT, owing to the similar method of heat-induced vascular damage.⁸

Sclerotherapy can treat a variety of vascular diseases, including the persistent embryonic veins in KTS.⁹ In sclerotherapy, catheter injection of a sclerosant, either alone or in combination with other minimally invasive techniques, damages the intimal wall of the vessel and induces thrombosis. A variety of agents can be used based on radiologist preference. Modern agents include polidocanol and sodium tetradecyl sulfate, which thrombose the target vessel while avoiding the local destruction and ischemia that can occur with the high doses of ethanol needed to treat large vessels.¹⁰ Complications of sclerotherapy, such as deep-vein thrombosis and extension of thrombosis past the target lesion into a deeper venous system, can occur. More severe complications can result in both transient and permanent neurological deficits, including visual disturbance, migraine, stroke, and, rarely, death.⁶ The expected rate of neurological disturbance is less than 2%, with permanent damage even more rare.⁶