Klippel-Trenaunay Syndrome

Klippel-Trenaunay (K-T) Syndrome is characterized by a localized or diffuse capillary malformation that overlies a venous malformation and/or lymphatic malformation with associated soft tissue and bone overgrowth (hypertrophy). The capillary malformation is typically substantial, varicose veins are often quite numerous, and bone and soft tissue hypertrophy is variable. The affected limb is either larger or smaller than the unaffected limb. Hypertrophy occurs most commonly in the lower limbs, but may affect the arms, the face, the head or internal organs. Additionally, a wide range of other skeletal and skin abnormalities sometimes coexists.

K-T is often limited to one limb, but may occur in multiple limbs and/or head or trunk area. Internal organs may be involved. Each case of K-T is unique and may exhibit the above characteristics to differing degrees. 

Complications may include bleeding, cellulitis, venous thrombosis, pulmonary embolism, lymphatic "blebs", skin breakdown and ulceration, vertebral scoliosis, gait abnormalities, joint damage, and chronic pain. Difficulty finding properly fitted clothing and/or shoes is common. Associated abnormalities such as macrodactyly, lymphedema, or involvement of the abdominal and pelvic organs may also occur. 

Etiology 

Studies published in early 2015 indicate a somatic mutation of the PIK3CA gene is involved in a group of closely related overgrowth conditions (K-T, CLOVES, M-CM, FAVA). These are referred to as PIK3CA Related Overgrowth Spectrum (PROS).

Treatment 

There is no known cure for K-T Syndrome. 

Conservative treatment of the symptoms at a multidisciplinary clinic is recommended. Compression garments and pumps help manage the effects of lymphedema and can assist in protecting the limb from trauma. Recent drug trials with Sirolimus have proven helpful in some cases. Laser therapy may reduce or eliminate port-wine stains and help control lymphatic blebs. Surgical procedures may be necessary to debulk excessive tissue, to excise ectatic veins or to correct uneven growth in limbs (epiphyseal arrest), for example.
 
Computed Axial Tomography (CAT) and Magnetic Resonance Imaging (MRI) scans, and color Doppler studies are useful in determining the scope of the syndrome and how best to manage it. Interventional radiologists may, in some cases, perform minimally invasive image guided treatment of vascular and lymphatic malformations, but this type of therapy is best performed by interventional radiologists with extensive experience and training in the field of vascular anomalies in a multidisciplinary clinic setting. 

Terminology 

The medical community at times has confused the conditions Klippel-Trenaunay and Parkes Weber syndromes, using the term Klippel-Trenaunay-Weber syndrome. Since the late 20th century it is recognized that Klippel-Trenaunay and Parkes Weber syndromes are entirely different conditions.

  • Parkes Weber involves capillary malformations overlying venous and lymphatic malformations, but also has fast-flow arterial malformations and shunting. Parkes Weber is caused by germline mutations in the RASA1 gene.  
  • K-T involves capillary malformations overlying slow-flow venous and lymphatic malformations. K-T is associated with somatic mutations in the PIK3CA gene.

 K-T is also referred to by an acronym describing the body systems affected—Capillary, Lymphatic, Venous Malformation (CLVM). 

For many years Klippel-Trenaunay Syndrome was a generic diagnosis for a broad spectrum of combined vascular malformation.  ISSVA (International Society for the Study of Vascular Anomalies) has advanced clarification and classification of these conditions. Even with the classifications there is often substantial crossover in presentation of PIK3CA Related Overgrowth Syndromes (PROS) and in other conditions with similar phenotype, resulting in inexact diagnosis. There is no specific test for K-T. 

Page last updated April 29, 2016