Klippel-Trénaunay-Weber-Syndrom

nicht verwechseln mit: Klippel-Feil-Syndrom

Klippel-Trénaunay-Weber syndrome (KTWS) is a syndrome combination of capillary malformations, soft-tissue or bone hypertrophy, and varicose veins or venous malformations. It is considered an angio-osteo-hypertrophic syndrome.

KTS classically comprises a triad of:

  • port wine nevi
  • bony or soft tissue hypertrophy of an extremity (localized gigantism)
  • varicose veins or venous malformations of unusual distribution

The diagnosis of KTS is usually made when any two of the three features are present. Capillary malformations may be absent in the atypical form .

Terminology

The name Klippel-Trénaunay-Weber syndrome (KTWS) is essentially misleading as the current consensus uses two different names to denote two different syndromes. However, they are not always consistently addressed as distinct entities in literature:

Epidemiology

Most cases of KTS are sporadic and there is no recognized gender or racial predilection. The prevalence of KTWS (as such including Weber) is ~1:100,000 .

Clinical presentation

Patients usually present in infancy. Features are often unilateral and typically affect one limb . It may be diagnosed in utero .

Pathology

Genetics

Most cases are considered sporadic. However, some of the possible differential diagnoses may have familial predispositions .

Clinicopathological spectrum

The following levels of severity of KTS have been suggested :

  • venous dysplasias/phlebectasic dysplasias
  • arterial dysplasias
  • arterial and associated venous dysplasias
    phlebarterectasia (no AV shunt)
    angiodysplasias with shunt (KTWS or actually F. P. Weber syndrome)
  • mixed angiodysplasias
    atypical form of KTS
  • Hypertrophy

    Enlargement of the extremity consists of bone elongation, circumferential soft-tissue hypertrophy or both. This often manifests as leg-length discrepancy, although any limb may be affected. Hyperostosis frontalis interna has also been associated with KTWS .

    Capillary malformations

    This is the most common cutaneous manifestation of KTS. Typically, capillary malformations involve the enlarged limb, although skin changes may be seen on any part of the body. The lower limb is the affected site in ~95% of patients.

    Varicose veins

    Present in a majority of patients with KTS, commonly located on the lateral aspect of the affected limb/leg  (and in some contradiction to common vena-saphena-magna varicosity).  Persistence of embryonic veins, of which the lateral marginal vein (the vein of Servelle) has been a most typical finding (68-80% of patients) .

    Venous malformations can occur in both the superficial and deep venous systems. Superficial venous abnormalities range from ectasia of small veins to persistent embryological veins and large venous malformations. Deep venous abnormalities include aneurysmal dilatation, aplasia, hypoplasia, duplications, and venous incompetence.

    Visceral manifestations

    Rectal and bladder hemorrhage are serious complications of pelvic vascular malformations and have been reported in 1% of cases. Vascular malformations can involve the

    • gastrointestinal tract (20%)
      • bleeding is the most common symptom and range from occult bleeding to massive, life-threatening hemorrhages and consumptive coagulopathy
      • the most frequently reported sites are the distal colon and rectum
      • upper gastrointestinal bleeding from jejunal hemangiomas may also occur
    •  genitourinary tracts
      • involved in more severe cases
      • the absence of severe limb varicosities or venous malformations does not preclude the presence of pelvic involvement
      • gross hematuria, which is recurrent and painless, is usually the first clinical sign of bladder involvement and frequently manifests early in life
      • renal hypertrophy and venous enlargement may occur ipsilaterally to affected side
      • vascular malformations are often located on the anterior bladder wall and dome
      • the trigone and bladder neck are rarely involved
      • genital lesions usually do not cause clinical problems for patients with KTS; however, some patients who report erectile dysfunction have abnormal penile veins
    • spleen
    Skeletal manifestations

    These are usually secondary to leg-length difference :

    Radiographic features

    May show a combination of any of the above mentioned clinical features.

    Intrauterine ultrasound

    Prenatal ultrasound may diagnose KTWS as early as 15week of gestation, based on limb hypertrophy and associated subcutaneous cystic lesions. 3D US may reveal leg width difference. Possible additional features include :

    Differentials for intrauterine imaging findings may include :

    Plain radiograph

    On conventional radiography, bone elongation contributing to leg length discrepancy, soft-tissue thickening, or calcified phleboliths may be seen.

    MRI

    T2-weighted MR images may show malformed venous and lymphatic lesions as areas of high signal intensity.

    MR imaging depicts deep extension of low-flow vascular malformations into muscular compartments and the pelvis and their relationship to adjacent organs as well as bone or soft-tissue hypertrophy.

    Angiography

    Typical angiographic findings, which may also be seen on contrast-enhanced CT-scan or MRI, include lower leg superficial varicoid drainage without a deep venous system. The marginal vein of Servelle is a pathognomonic finding (a subcutaneous vein found in the lateral calf and thigh) .

    Complications

    • thrombophlebitis of the affected limb
    • venous thromboembolism
    • gastrointestinal or genitourinary hemorrhage if there is visceral involvement (see above)
    • If capillary malformations are large enough, they may sequester platelets, possibly leading to the Kasabach-Merritt syndrome (consumptive coagulopathy)

    Treatment and prognosis

    Treatment in a majority of patients is conservative and includes application of graded compressive stockings or pneumatic compression devices to the enlarged extremity. Percutaneous sclerosis of localized venous malformations or superficial venous varicosities may be indicated in some patients. Surgical treatment may include epiphysiodesis to control leg length discrepancy, excision of soft tissue hypertrophy, and stripping of superficial varicose veins.

    History and etymology

    In 1900, the French physicians Klippel and Trénaunay first described a syndrome characterized by a capillary nevus of the affected extremity, lateral limb hypertrophy, and varicose veins. In 1918, Weber noted the association of this triad with arteriovenous fistulas .

    See also