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Special Feature
July 6, 2009

Picture of the Month—Diagnosis

Arch Pediatr Adolesc Med. 2009;163(7):665. doi:10.1001/archpediatrics.2009.114-b
Denouement and Discussion: Klippel-Trénaunay Syndrome

Klippel-Trénaunay syndrome (KTS) is a rare disorder characterized by the triad of port-wine stain, hypertrophy of bone and soft tissue, and varicose veins or venous malformations. The syndrome was described in 1900 by French physicians Klippel and Trénaunay.1In 1907, Weber2noted similar findings in association with arteriovenous malformations.

The diagnosis of KTS can be made when any 2 of the 3 features are present. Jacob et al,3in a study of 253 patients with KTS, observed that 63% of the patients had all 3 features and that 37% had 2 of the 3 features. Port-wine stain has been observed in 98% of patients, varicosities or venous malformation in 72%, and limb hypertrophy in 67%.

The exact cause of KTS is unknown, although several theories exist. Most cases are sporadic, and a few cases could be of autosomal dominant inheritance. A new theory of paradominant inheritance was suggested in a study of monozygotic twins.4A novel mutation in the RASA1gene (OMIM139150) was found in KTS.5

No racial or sex predilection for KTS has been documented. The syndrome is present at birth or develops during early childhood and generally affects a single extremity. The lower extremity is the most commonly affected site (95% of patients), followed by the arms and the trunk.

The most common manifestation is capillary hemangioma or port-wine stain. Usually the hemangioma has a distinct border that follows the midline and is generally noted on the lateral aspect of the limb. Typically, the capillary vascular malformation does not progress or it regresses with time. The hemangioma can have cutaneous or deep involvement (osseous and muscular). Visceral organs such as spleen, bladder, liver, pleura, and gastrointestinal tract may also be affected.6Involvement of the gastrointestinal tract has been described in 20% of patients; bleeding of the distal colon and rectum is the most common symptom. Genitourinary involvement (hematuria) also may be noted in KTS.

Varicosities or venous malformations often spare the saphenous distribution, sometimes in the pelvic region. Varicose veins can be superficial, deep, or perforating. Venous stasis results from valvular insufficiency, obstructed venous outflow, or abnormal lymphatic drainage.

Bony and soft-tissue hypertrophy is another feature of KTS; increased length and circumference of the affected extremity are typical. Hypertrophy may be present at birth and progresses with time. Complications of KTS include stasis, bleeding, ulcerations, dermatitis, cellulitis, thrombophlebitis, pulmonary emboli, and abnormalities of the vertebral column.

The diagnosis of KTS is made on the basis of clinical history and findings at physical examination. Typical hemangioma associated with bony and soft-tissue hypertrophy or abnormal venous structure is sufficient for the diagnosis. A skin biopsy specimen of the hemangioma is unnecessary for the diagnosis.

If complications are present or suspected (eg, deep venous thrombosis), imaging studies such as color Doppler ultrasonography and magnetic resonance imaging can be useful. Radiographic examination can be used to define bony hypertrophy and to measure the difference in the length of the affected extremity. Imaging studies of the abdomen are required to rule out a vascular malformation in the perineum or abdomen.7The most common differential diagnoses are Parkes Weber syndrome and proteus syndrome.

Medical treatment of KTS is conservative and symptomatic. Some patients with KTS have severe pain in the affected limb.8A multidisciplinary approach is necessary when complications are present. Compression garments are required to treat chronic venous insufficiency and lymphedema. Cellulitis and thrombophlebitis are treated with elevation, compression, and analgesic and antibiotic therapy. Skin hygiene is useful in preventing cellulitis. In women with KTS, it is recommended that, to prevent deep venous thrombosis, estrogen-containing contraceptives not be used.

In addition to medical treatment, if limb discrepancies are present, surgical orthopedic procedures may be considered to prevent functional and psychologic disabilities; laser treatment of the skin lesions could be useful in treating the superficial component of the hemangioma to improve its color. Surgical treatment of varicosities is controversial. Yearly clinical follow-up of patients with KTS is recommended, with more frequent follow-up if clinically indicated.

Insofar as long-term outcome, hypertrophy of the limb is the most common problem, often impairing function and affecting mobility. All children with KTS must be monitored for growth abnormalities. An important issue is pain, which can worsen and seriously affect quality of life8and requires psychologic support. When the limb is grossly enlarged, amputation may rarely be required.9

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Correspondence:Andrea E. Scaramuzza, MD, Department of Pediatrics, Azienda Ospedaliera, “Ospedale Luigi Sacco,” University of Milan, Via G. B. Grassi 74, 20154 Milan, Italy (scaramuzza.andrea@hsacco.it).

Accepted for Publication:October 21, 2008.

Author Contributions:Dr Scaramuzza had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Mameli, Scaramuzza, Riboni, De Palma, and Zuccotti. Acquisition of data: Mameli and Tadini. Analysis and interpretation of data: Mameli, Scaramuzza, Tadini, and Riboni. Drafting of the manuscript: Mameli and Scaramuzza. Critical revision of the manuscript for important intellectual content: Scaramuzza, Tadini, Riboni, De Palma, and Zuccotti. Administrative, technical, and material support: Mameli, Scaramuzza, Tadini, Riboni, De Palma, and Zuccotti. Study supervision: Mameli.

Financial Disclosure:None reported.

Klippel  MTrénaunay  P Du naevus variquex osteohypertrophique.  Arch Gen Med 1900;3641- 672
Weber  FP Angioma-formation in connection with hypertrophy of limbs and hemi-hypertrophy.  Br J Dermatol 1907;19231
Jacob  AGDriscoll  DJShaughnessy  WJStanson  AWClay  RPGloviczki  P Klippel-Trénaunay syndrome: spectrum and management.  Mayo Clin Proc 1998;73 (1) 28- 36PubMedCrossref
Hofer  TFrank  JItin  PH Klippel-Trénaunay syndrome in a monozygotic male twin.   Eur J Dermatol 2005;15 (5) 341- 343PubMed
Hershkovitz  DBercovich  DSprecher  ELapidot  M RASA1mutations may cause hereditary capillary malformations without arteriovenous malformations.  Br J Dermatol 2008;158 (5) 1035- 1040PubMedCrossref
Cha  SHRomeo  MANeutze  JA Visceral manifestations of Klippel-Trénaunay syndrome.  Radiographics 2005;25 (6) 1694- 1697PubMedCrossref
Elsayes  KMMenias  CODillman  JRPlatt  JFWillatt  JMHeiken  JP Vascular malformation and hemangiomatosis syndromes: spectrum of imaging manifestations.  AJR Am J Roentgenol 2008;190 (5) 1291- 1299PubMedCrossref
Lee  ADriscoll  DGloviczki  PClay  RShaughnessy  WStans  A Evaluation and management of pain in patients with Klippel-Trénaunay syndrome: a review.  Pediatrics 2005;115 (3) 744- 749PubMedCrossref
Pawel  BRSpencer  KDormans  J Klippel-Trénaunay syndrome.  Arch Dis Child 2005;90 (11) 1127PubMedCrossref