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 are 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 (some K-T, CLOVES, M-CM, FAVA, FIL, CLAPO, macrodactyly, lymphatic malformations). These are referred to as PIK3CA Related Overgrowth Spectrum (PROS).

In some people, PIK3CA is not the gene that causes their K-T. Some will find GNAQ, TIE2, PIK3CR1, or other mutations. The full scope of genetic information on K-T is not yet clear. The term Klippel-Trenaunay is from the early 1900's so it is associated with a set of symptoms, not a genetic diagnosis. All of K-T is still under study so it is possible new clusters of people sharing genetics and specific symptoms will be identified and new condition names identified as the genetics are clarified.

K-T has been a diagnosis used for what is now recognized as a broad range of conditions with similar symptoms - capillary, venous, and lymphatic malformations with bony and soft tissue growth irregularities, plus many other symptoms. K-T exists as it was originally described - capillary, venous, and lymphatic malformations with bony and soft tissue growth irregularities. Other significant symptoms that are not related possibly indicate that the diagnosis should be one of the similar conditions. The importance of having an accurate diagnosis is that even subtle differences in a condition might call for a different management protocol. While most K-T patients are not exactly alike, symptoms are not as broad as once thought.

A PROS diagnosis for K-T should not be assumed unless genetic testing has confirmed the presence of PIK3CA.

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 were successful in proving Sirolimus helpful for management in some cases. More inhibitors are under investigation and are promising. 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 the presentation of PIK3CA Related Overgrowth Syndromes (PROS) and in other conditions with a similar phenotype, resulting in inexact diagnosis. There is no specific test for K-T.

Page last updated April 29, 2021