Klippel-Trenaunay Syndrome

Definition

  • The association of three physical findings including
  1. capillary malformation,
  2. varicosities or venous malformation,
  3. hypertrophy of bony and soft tissues predominantly the limbs
  • This triad with the addition of arteriovenous malformation is known as Parkes Weber syndrome.
  • prognosis is generally benign and the management is primarily supportive unless symptoms of hematuria, hematochezia, or esophageal varices arise.

Pathogenesis

  • Klippel- Trenaunay syndrome has no known direct hereditary factors but may be inherited on a multifactorial basis. As a result, the etiology of this syndrome remains hypothetical, obscure, and controversial
  • Theories:
  1. intrauterine damage to the sympathetic ganglia or intermediolateral tract leading to dilated microscopic arteriovenous anastomoses (Bliznak and Staple)
  2. Venous hypertension that develops as a result of a congenital deep vein anomaly consisting of atresia, hypoplasia, or vascular agenesis; and compressionby abnormally placed muscles or fibrovascularcords. (Servelle)
  3. The mesodermal abnormality theory(Baskerville) would explain all three symptomatic features of Klippel-Trenaunay syndrome. A partial persistence of the embryologic vascular system would cause an augmentation of blood flow, resulting in an increased temperature to the involved limb that in turn would increase the circumferential size and elongation of the limb. Furthermore, this may cause the histologic vascular changes that later in life become apparent as varicosities and capillary malformations
  4. Mixed mesodermal and ectodermal dysplasia (McGrory and Amadio)

Incidence

  • Most cases are sporadic, few cases of AD

.

Clinical

  • diagnosis can be made on at least two of the three cardinal features.
  • In a series of 252 patients at the Mayo Clinic
  • 63% of patients had all 3 features and 37% had 2 of the 3 features.
  • Port-wine stain was seen in 98% of patients
  • varicosities or venous malformations in 72%,
  • limb hypertrophy in 67%.
  • generally affects a single extremity, although cases of multiple affected limbs have been reported.
  • The most common limbs involved are the lower extremities (88 to 95%), followed by the upper extremities (5%).
  • Unilateral involvement occurs in 85% of cases.
  • Upper and lower extremity combined involvement occurs in 15 percent.
  • Very rarely, four extremity involvement has been reported.

Capillary hemangioma or port-wine stain usually presents first.

  • has a distinct, linear border that respects the midline.
  • Hemangioma is often noted on the lateral aspect of the limb.
  • Skin changes usually occur on the same side as the affected limb (85 %); however, it is not uncommon to have additional capillary malformations occurring on the contralateral limb or in another area of the body such as the trunk or head and neck.
  • Although the capillary malformation is usually confined to the skin may see involvement of subcutaneous tissues, muscles, and abdominal and thoracic cavities.
  • Some patients may undergo depigmentation or “fading” of the malformation as a result of capillary thromboses, whereas others progress to additional skin changes such as atrophy, eczema, verrucae, hyperhidrosis, bleeding, and infections.
  • Although complete disappearance of the capillary malformation does not occur, aging may result in significant “fading” of the malformation.
  • Puberty and pregnancy may exacerbate the capillary malformation.

Varicose veins

  • Abnormalities described are hypoplasia, agenesis, valvular incompetence, and aneurysmal dilatation of the deep venous system
  • Without supportive care, these varicosities may be painful, tender, and worsen symptomatically with increasing age.
  • At times, ulcerations develop that may result in a superficial thrombophlebitis or cellulitis
  • Patches of lipodermatosclerosis may also occur
  • The vein of Serville (70%) is a large, lateral, superficial vein sometimes seen at birth. This vein begins in the foot or the lower leg and travels proximally until it enters the thigh or the gluteal area (lumbar to foot pattern)
  • In the majority (33 percent) of cases, the lateral vein will extend to the full length of the leg, terminating into the internal iliac system through the gluteal veins.
  • In the rest of the patients, the lateral vein is variable in distance, terminating in decreasing frequency in the profundus femoris vein, superficial femoral vein, popliteal vein, and external iliac vein.
  • Varicosities may be extensive, though they often spare the saphenous distribution
  • Surgical exploration has demonstrated atresia and agenesis of deep veins, compression due to fibrous bands, aberrant arteries, abnormal muscles, or venous sheaths.

Bony and soft tissue hypertrophy

  • secondary to increased length (bony involvement) and/or increased girth (soft tissue involvement)
  • usually progresses during the first years of life. A greater degree of hypertrophy may be seen in patients with coexisting arteriovenous malformation
  • discrepancy in limb length is secondary to long-bone growth (i.e., femur and/or tibia).
  • The increasing limb girth is primarily caused by soft-tissue hypertrophy and, to a lesser extent, muscular hypertrophy accompanied by increasing vascular tissue and skin thickness.

Arteriovenous fistulas, (Parkes-Weber syndrome)

  • Addition of large hemodynamically significant AVMs. Small insignificant AVMs fall into the definition of KTS.
  • rarely found in the affected extremity
  • If present, they can occasionally be palpated as a pulsatile mass, thrill, or bruit on physical examination.
  • Hyperthermia and a positive Branham sign (bradycardia with the application of compression on an artery proximal to the malformation) are also indicators of an arteriovenous malformation.

Associated Abnormality

  • The major associated malformations seen inKlippel-Trenaunay syndrome are generally dividedinto vascular, skeletal, cutaneous, and lymphatic
  1. skeletal findings: the mostcommonly (29 percent) associated abnormalitiesfound were dislocation of the hip and syndactyly.
  2. vascular: hematochezia (GI bleed) and hematuria,and esophageal variceal bleeding, although rare, but very serious findings. Vaginal and vulvar hemorrhagingare not as serious, but may be problematic. Hematochezia is considered the most commonform of bleeding in Klippel-Trenaunaypatients, and its pathophysiologic characteristicsare intriguing - related to the connection between these veins and the internal / ext iliac system. When these get overloaded back pressure into the rectal veins leads to varicosities and bleeding.
  3. Lymphatic abnormalities are common andcan be extremely disabling. The lymphatic anomalies most commonly observedare lymphatic aplasia, hypoplasia, and reductionof both lymphatic trunks and nodes.The resulting signs appear as either lymphedemaor cutaneous lymphatic vesicles that occur secondaryto backflow from an obstructed or congesteddeep lymphatic system.

DIAGNOSIS AND TREATMENT

  • Management andtreatment of this disease is generally supportiveunless the patient becomes overly symptomaticor disabled.
  • Although the majority of Klippel-Trenaunay patients will complain of physicaldisturbances, approximately 25% willapproach the physician for cosmetic reasons.

Capillary Malformation

  • In general, capillary malformations are leftalone unless they become progressively symptomatic.
  • Skin breakdown and ulcerations withsubsequent bleeding may lead to surgical excisionof the overlying skin. Although this may bea direct approach to the malformation, it isimportant to note that the affected skin healsrather poorly
  • Hence, any resection of themalformation should be performed with cautionin trying to minimizing excessive scar formationand the likelihood of wound-healingcomplications.
  • Light-colored malformations can be successfullycamouflaged with appropriate cosmeticproducts, whereas more intense and darkcoloredmalformations require a more aggressiveapproach.
  • pulse dye lasers have made animpact in the treatment of malformations.
  • The new pulse dye lasers have been adjustedwith a longer wavelength, which has provided agreater depth of dermal penetration, withoutcompromising vascular specificity. Thus, theheat produced by the laser is targeted towardvascular structures and not to adjacent normalelements. Managing malformations by meansof this method requires a half dozen or moretreatments with 6-week intervals.
  • Malformationsof the bladder in patients with Klippel- Trenaunay syndrome resulting in hematuriahave also been successfully treated with aneodymium:yttrium-aluminum-garnet laser, resultingin excellent tissue coagulation.

Varicosities

  • Ligation and stripping of varicosities is rarely recommended and should be performed only after careful invasive radiologic review of the venous outflow of the extremities.
  • Generally, varicosities are managed supportivelywith intermittent rest, elevation, reassurance,and continued reinforcement in wearinggraduated compressive stockings. Thrombophlebitisor cellulitis should be treated nonoperativelywith analgesics and antibiotics, respectively.

Surgery

  • When conservative measures becomerealistically resistant, both aggressive and invasiveforms of treatment may be used
  • Before surgical treatmentof any varicosities, radiographic examinationis required. The most effective imaging techniquesused are venography and magneticresonance imaging. Duplex venograms shouldbe obtained in all cases before surgical interventionsto visualize the entire venous anatomy forvenous anomalies, valvular incompetence, andpersistent embryologic veins.
  • Large varicositiesshould never be ligated or stripped, especiallywhen the deep venous system is found to beeither partially or completely atretic. The suprapubicveins should never be resected becausethey serve as a substitute channel for the atreticiliac vein.
  • Most surgical procedures performedwith the intention of improving varicosities are temporary and short-lived and frequentlyworsen the condition.

percutaneous injection of sclerosingagents

  • Agents: sodium tetradecyl sulfate andabsolute alcohol.
  • This method promotes irritationof the endothelium, obliterating thevessel lumen and resulting in fibrosis. Sclerotherapymay be facilitated by color-duplex imaging
  • Because some veins recanalize (18 percent),31multiple injections (up to 30 in some cases) maybe required at appropriate intervals (4 to 6weeks), allowing the inflammatory responses tosubside.
  • Eventually, with an appropriate sclerosingprotocol, almost half (44 percent) of venousmalformations disappeared and greater than aquarter (28 percent) diminished.

contralateral saphenous vein transplant

  • Successful treatment of incompetent valves in the femoral vein of the affected limb with contralateral saphenous vein transplant has been reported.

Endovenous laser therapy

  • Endovenous laser therapy of the greater saphenous vein is gaining support for the management of varicosities in the general public and in patients with KTWS.
  • This therapy has been used alone and in combination with other surgical interventions. It is a novel and minimally invasive approach for the management of some varicosities.

Hypertrophy and Elongation

  • Serial scanograms and computedtomography may be used to measure limb length and to determine the best time forlength equalization procedures such as epiphysealstapling and femoral shortening. Extremitydiscrepancy of 2 cm or less may be easilymanaged by using a shoe lift on the contralateralside to compensate for the discrepancyand the possible development of scoliosis.
  • Extremity discrepancy of 2 to 3 cm or more islikely to result in significant ambulatory difficulties,abnormal posturing, and contralateralcompensatory changes, resulting in an unphysiologicgait. These discrepancies should be addressedby means of limb-shortening proceduresbefore they cause permanent andirreversible consequences.
  • Although technicallychallenging and plagued with various significantcomplications, arresting epiphysealgrowth is performed by either stapling orepiphysiodesis. Stapling is considered unreliable,unpredictable, and fraught with numerouscomplications.
  • Epiphysiodesis as describedby Mulliken and Young is considered to bereliable and permanent, provided that measurementsand predictions are made accurately.
  • Both femoral and tibial shortening areadditional methods effective in shortening lower limbs and at the same time reducing theperiod of immobilization that is so frequentlyrequired with these procedures.
  • Serville advocates contralateral ligation of deep veins – he performed ligation of thepopliteal vein in the normal limb on 48 children,with differences in lengths between thetwo limbs significantly reduced or even absentby adult life
  • Upper extremity disparity is rarely severeenough to be noticed by both patients and thus rarely requires surgical intervention.
  • Uncommon major digital deformitiesresulting in significant functional disabilitiesand unmanageable skin complications may betreated by amputation. This is not the casewhen major grotesque and functionally disablingextremities beneficial

Bleeding

  • Surgically correcting hematuria and hematocheziainvolves releasing the superficial femoraland deep femoral veins from their adherenceto nearby muscles. This allows a free flowwithin these veins that, in turn, allows decompressionof the inferior limb. This can only beachieved if the abnormality does not also lie onthe agenesis of the anterior venous system. Furthermore,one should keep in mind that theretroadductor vein forms an anastomosis withthe sciatic vein. This in turn facilitates decompressionof the internal iliac system by reducing these overload phenomena.
  • If the abovesurgical treatment is not feasible, one may need to rely on performing a rectosigmoidectomyor a hemorrhoidectomy, the latter ofwhich usually does not have adequate longtermbenefits.
  • Hematuria may be managed bya partial or total cystectomy.
  • Esophagealvariceal bleeding caused by portal vein hypoplasiamay be surgically corrected by performinga splenorenal shunt

Lymphedema

  • Lymphedema therapy can be divided intoconservative and operative management, the former being the most common.
  • Initial managementof lymphedema begins by extensivelyeducating both patient and family on the basicsof skin hygiene, with the end goal of minimizingskin infections.
  • Combination of physicaltherapies, which include manual lymphedematreatment, remedial exercises, and compressionapplied with multilayered bandage wrapping,can be extremely beneficial.
  • Additionaltherapy is performed in the way of intermittentpneumatic compression, thermal therapy, elevationof the involved extremity, and drug therapy,which involves the use of diuretics, oralbenzopyrones, and antibiotics.
  • Operativemanagement involves “debulking” of excessskin and subcutaneous tissue, performing reconstructivemicrosurgical procedures withwhich interpositional vein segments to restorelymphatic continuity are achieved, or creationof lymph-venous and lymph-nodal shunts toimprove lymphatic transport.
  • Debulking procedures have limited use and may damage venous and lymphatic structures, leading to increased edema in the affected limb.