Overview

Klippel -Trenaunay syndrome ( KTS ) - sounds intimidating? Not often you may come across this term. Don’t worry we've got you covered. KTS syndrome is a rare condition that is usually present from birth and is associated with abnormalities in vascular-related structures like blood vessels. Along with blood vessels, KTS also affects the soft tissues and bones. It is estimated to affect approximately two to five individuals out of every 100,000 around the world equally affecting both sexes. There is a distinct triad of symptoms associated with KTS: port wine stains, varicose veins and limb overgrowth. It is usually best if this condition can be diagnosed and treated early, as they can significantly reduce the risk of complications. In this article, we will explore KTS with a main focus on the triad of symptoms.^1,2,3,4

Causes

KTS relates to a mutation in the PIK3CA gene which disrupts normal vascular development. While the reason for this mutation is unknown, it is reassuring to know that despite being present from birth, it is not passed on from parents.⁶

Symptoms

Syndrome usually means a collection of symptoms. Thus, the hallmark of KTS is a triad of symptoms namely, port wine stains, varicose veins and limb overgrowth ( hypertrophy ) as mentioned at the beginning of this article.^1,4,5 Let's delve a bit further into these three symptoms in detail : 

• Port wine stains - These are skin manifestations of the KTS syndrome which resembles very much closely to a birthmark. They appear flat and range from pink to dark reddish-purple in colour. The colour may darken over the years especially in relation to traumas. These are usually present as a result of swelling of the capillaries that are directly beneath the skin. Port wine stains can be the first noticeable feature of KTS that is found on the affected limb usually. 
• Varicose veins - Veins are blood vessels that usually carry deoxygenated blood back to the heart. In KTS the veins of the leg especially will become swollen and tortuous due to abnormal vein development resulting in pooling of blood. In severe case scenarios, KTS can affect the deep veins, increasing the risk of deep vein thrombosis.
• Limb overgrowth - Limbs usually consist of bones and soft tissues. Individuals with KTS can have overgrowth in both bones and soft tissues. Hence, limb development will be abnormal. Limb overgrowth has an asymmetrical involvement thus affecting only one leg. Mostly, the legs are more involved than the hands with KTS. This can lead to differences in limb length, gait issues, joint problems, and difficulty finding properly fitting clothing or shoes.

Other symptoms associated with KTS 

• Lymphatic malformation - Individuals with KTS can sometimes have problems with the lymphatic system affecting the lymphatic drainage. The lymphatic fluid may leak in some instances causing swelling or issues in the pelvis, bladder and/or lower intestines⁷
• Pain
• Skin ulceration (damage)
• Recurrent infections like cellulitis
• Problems related to mental well-being due to the bodily aspect of the KTS

Diagnosis

KTS is a clinical-based diagnosis which means it is entirely based upon observable symptoms and physical features, hence if you notice any of the above-mentioned symptoms or features in this article it's best to consult with your local healthcare provider. This diagnosis can be supported using investigations such as CT / MRI scans to look into soft bones and tissues, Doppler Ultrasound scan that evaluates the blood flow and angiograms which help to visualize blood vessels.¹

Differential diagnosis

Sometimes there can be similarities between diseases, especially due to overlapping of symptoms, thus causing confusion. Below are some conditions that may present with similar features to KTS and need to be excluded by your healthcare professional ^1,8

• Parkes Weber Syndrome (PWS) - A few arteriovenous malformations can be found in KTS even though it holds less significance clinically. In contrast, PWS consist of multiple arteriovenous malformations which is one of the hallmarks of PWS
• CLOVES Syndrome - Part of the same PIK3CA-Related Overgrowth Spectrum (PROS), CLOVES includes fatty tissue overgrowth and vascular malformations, often involving the trunk. It may also include spinal and neurological issues not typically seen in KTS

Treatment

As KTS involves blood vessels, soft tissues, and bones holistic management is required thus multidisciplinary care.^1,8 A team of specialists are involved, also known as a multidisciplinary team (MDT) that consists of: 

• Dermatologists - Speaclises in dealing with the skin manifestations
• Vascular surgeons - Speaclises in  dealing  with problems relating to blood vessels such as varicose veins or complications such as DVT
• Orthopaedic surgeons and physiotherapists-They  work together to help achieve limb mobility
• Psychologists or counsellors for emotional support,
• Pain specialists
• Radiologists

Individuals with KTS may be prescribed blood thinning medications and advised to wear compression stockings to prevent blood clot formation in the legs. To reduce vascular malformation drugs like Sirolimus may be prescribed. Treatment procedures like endovenous ablation and sclerotherapy can be used to address any further problems resulting due to veins, especially varicose veins. The appearance of port wine stains can be improved using laser therapy usually resulting in lightening the appearance of the port wine stain. Asymmetry of limbs can be adjusted using assistive objects like shoe lifts or surgery can be suggested to correct any overgrowth-related issues of the limb.

There are several support groups available to help individuals with KTS : 

• “K-T support group” - A USA-based organisation affiliated with NORD ( National Organisation for Rare Disorders ) established in 1986. The group offers resources such as educational materials, and a periodic newsletter, and organizes biannual conferences to facilitate information exchange among members
• “Klippel-Trenaunay Weber Syndrome (KTWS) Support Group” – A Facebook group/an online platform set up for reaching out to similar individuals with KTS
• “Vascular Birthmarks Foundation” (VBF) - Not exclusively a foundation for KTS but it involves resources and support for individuals with vascular birthmarks, anomalies, and related syndromes, including KTS

Summary

Klippel-Trenaunay Syndrome ( KTS ), belonging to the category of rare genetic disorders, is caused by a mutation in the PIK3CA gene. The PIK3CA gene instructs the production of a protein that is responsible for the regulation of cell growth, division and survival. It usually presents itself from birth mainly in the form of a triad of symptoms such as port wine stains, varicose veins and limb overgrowth. Other associated tissues may include lymphatic malformations, skin ulcerations and recurrent infections along with pain. KTS is diagnosed purely clinically; there are a few investigations that can be done to support the diagnosis such as scans, doppler studies and angiograms. It is also necessary to rule out other syndromes like Parkes-Weber Syndrome and CLOVES syndrome before concluding the diagnosis. Treatment involves a MDT team to provide symptomatic care in terms of medicines such as blood thinners, compression stocking as well as laser therapy to physiotherapy and shoe lifts and even in some cases surgery. There is always psychological and community support available that can be easily found on Facebook. Although there is an unavailability of a cure for KTS syndrome at the moment, it's often highlighted in literature about how the importance of early detection and intervention can play a significant role in optimizing outcomes from the syndrome.

FAQs

Is Klippel - Trenaunay Syndrome life threatening?

KTS is not a life threatening condition but if diagnosed early it can help to prevent some serious complications such as DVT and infection.

Does KTS affect life expectancy?

Though KTS presents itself from birth, it usually has a normal life expectancy. In addition, regular follow ups and proper treatment and care can prevent disease progression thus complications which can affect the life expectancy.

Is amputation necessary in KTS?

Amputation is not mandatory with KTS except with complications such as non-healing ulcers, recurrent infections, or debilitating pain that are unmanageable by other means.

Can children with KTS live a normal life?

Definitely, children with KTS can have a nearly normal and fulfilling life with the help of proper care through MDT.