Klippel - Trenaunay Syndrome is a congenital vascular disorder of unknown cause. Klippel-Trenaunay (KTS) is characterized by a triad of signs: Port Wine Stain (capillary malformations) covering one or more limbs, vascular anomalies, usually venous varicosities or malformation and hypertrophy (enlargement of the limb) or atrophy (withering or smaller limb). KT involves the lower limbs in about 90% of the patients. In rare instances, there is an absence of Port Wine Stain and not all three abnormalities need always be present for the syndrome to exist. Each case of KT is different, with patients having varying abnormalities and severity. Other associations with KT can include internal organ involvement, hematuria (blood in the urine) rectal bleeding and vaginal bleeding. Bleeding from an abnormal lesion on the affected limb is also common. Patients may have symptoms including anemia, coagulation problems (blood clots) and platelet trapping in the affected limb. (from the Sturge-Weber Foundation at http://www.sturge-weber.com)

The following is from the The Klippel-Trenaunay Syndrome Support Group Web Site

KLIPPEL-TRENAUNAY SYNDROME
"Moodie, D., Driscoll, D., Salvatore, D., Peripheral Vascular Disease in
Children, In:Young, J., Olin, J., Bartholomew, J., Peripheral Vascular
Diseases, 2nd Edition, Mosby Yearbook Publishers, 1996, p541--552."

Klippel-Trenaunay Syndrome (KTS) consists of a triad of cutaneous capillary hemangioma, bone and soft tissue hypertrophy, and venous varicosities (1). The etiology of KTS is unknown but some authors have suggested that it results from a mesodermal abnormality that occurs during fetal development leading to the maintenance of microscopic arteriovenous communications in the limb bud (2). Most commonly it is a sporadic event. Although there have been a few cases reported in which more than one family member supposedly had the syndrome other authors suggest that this may have not been the case (3,4). It has been suggested that KTS could result from the action of a mosaic gene abnormality that is lethal to the gamete when present in all cells of the embryo (5). We have seen two patients with intriguing associations. One patient has prolonged QT interval syndrome and the other a translocation of chromosome 8 and 14. Whether these are coincidental abnormalities or provide a clue to the location of a causative gene is unknown.

KTS should be distinguished from Parks-Weber Syndrome. In Parks-Weber Syndrome there are clinically apparent and important arteriovenous fistulae where as in KTS any arteriovenous fistulae that exist are microscopic in size and unassociated with the typical clinical findings of arteriovenous fistulae. The natural history of these syndromes are different. For example, because patients with KTS do not have arteriovenous fistulae, high output cardiac failure does not occur.

The manifestations of KTS are variable (fig 1-3). In a study of 144patients evaluated at the Mayo clinic (6), 132 had lower extremity involvement, 37 had upper extremity involvement, 21 had pelvic and abdominal involvement, 25 had involvement of the thorax and 7 had head and neck involvement(Table 1). In the same study 110(76%) had varicosities, 137(95%) had hemangiomas, and 134 (93%) had limb hypertrophy...

With occasional exceptions, the appearance of the baby shortly after birth will define the ultimate appearance of the child and young adult. The exceptions to this include: a) the cutaneous capillary hemangioma (port wine stain) may become lighter or darker; b) dark small nodular escrescence may develop on the skin; c) as growth occurs the limb length discrepancy may increase; d) some of the apparent increased mass may regress as baby fat regresses; e) subcutaneous masses may appear; and f) venous varicosities and, possibly dependent lymphedema will become more prominent with time. Parents should be reassured, however, that unaffected extremities and organs will not become affected the future.

CLINICAL MANIFESTATIONS
VENOUS VARICOSITIES AND MALFORMATIONS

The venous involvement in KTS can range from subtle abnormalities to massive varicosities and absence of important deep venous structures. The venous abnormalities usually involve the affected extremity and are apparent as superficial varicose veins. Dilation of superficial varicose veins may be unapparent in infancy but become apparent with increasing age. Not all patients with KTS have superficial venous varicosities.

In addition to superficial varicosities, many patients have abnormalities of the deep venous system of the extremity. The deep venous abnormalities can include dilation of the deep veins, absent venous valves, hypoplasia of the veins, and complete absence of the deep venous system. It is critically important to ascertain the status of the deep venous system if one is considering removal of superficial varicosities since the superficial venous system cannot be removed if the deep venous system is inadequate to provide venous drainage of the extremity. Because of the venous malformations some patients with KTS can develop thrombophlebitis.

Venous varicosities also can involve intraabdominal and intrapelvic organs. In Gloviczki's series, 10% of the patients manifest rectal bleeding and 3% had hematuria (6). Others have reported that 20% of their patients have had rectal bleeding, 10% had hematuria and 33% had evidence of abnormal intrapelvic veins(7). Venous or arteriovenous malformations have been described in other locations in rare patients with KTS. These include bone, spinal and intracranial locations.

In addition to the complete absence of the deep venous system of an extremity, absence of the inferior vena cava has been reported (8) and we have observed absence of the internal jugular veins.

LYMPHATIC ABNORMALITIES

Many patients with KTS have abnormalities of the lymphatic system. Since in no series of patients have these abnormalities been looked for in a systematic fashion the incidence of lymphatic abnormalities is unknown. In one series it was reported that 20% of patients have cutaneous vesicles which leak lymph. However in our experience exudation of lymph is less common. It frequently is unclear if the edema of an affected dependent extremity is a result of venous insufficiency, abnormal lymphatic drainage or a combination of the two. Some patients do develop soft tissue masses that are reminiscent of cystic hygromas. These masses can occur on an effected extremity or over the trunk, head, or neck

CAPILLARY HEMANGIOMAS AND OTHER CUTANEOUS LESIONS

There is a broad spectrum of cutaneous manifestations of KTS. Most commonly there is a port wine stain which can be very light in color to deep maroon. This lesion can be flat or elevated. The integrity of the skin over the hemangioma may be excellent or poor. In some cases the capillary hemangioma is raised considerably from the surface and may be verrucous in nature. Some areas of the malformation may be prone to skin breakdown, bleeding, and infection. In general the intensity of the color of the hemangioma lessens as the child ages. However, some patients develop dark (deep blue to black) 1-2 mm nodules on top of the hemangioma or, at times, over seemingly unaffected portions of skin. These can be quite friable and prone to spontaneous bleeding or bleeding after minor trauma. Cutaneous or subcutaneous cavernous hemangiomas occur in 40% of patients(1). These can produce a spongy feel to the skin and frequently are associated with lymphangiomas
Other cutaneous manifestations of KTS include phlebectasias, hyperhidrosis, hyperthermia and hypertrichosis. Patients with KTS are prone to cellulitis. It is unclear if these episodes are always secondary to bacterial infection or to a local inflammatory response in response to pockets of lymph accumulation.

BONE AND SOFT TISSUE HYPERTROPHY

In Gloviczki's series, 95 of 144 patients had one extremity longer than the other and 100 of 144 patients had a swollen or circumferentially enlarged extremity (6). Most commonly a lower extremity is affected but in a forth of the patients an upper extremity is involved. Usually the longer, bigger extremity is also the extremity that exhibits the skin and vascular changes but occasionally the extremity with skin and vascular involvement is the shorter or smaller extremity. The bony hypertrophy may effect all the bones in an extremity or be limited to one or two bones. Some patients may have macrodactaly.
In addition to bony hypertrophy, many patients have soft tissue hypertrophy. This can be quite limited; for example to a localized mass on the back or chest, or can be quite widespread; for example involving an entire arm or leg. The soft tissue hypertrophy is usually fatty and contains variable amounts of venous structures.
Other limb findings that have been described in KTS include syndactyly, clinodactyly, polydactyly, split hand deformity, metatarsal and phalangeal agenesis, osteolysis, congenital dislocation of the hip, and peripheral neuropathy (1).

HEAD, CENTRAL NERVOUS SYSTEM AND EYE INVOLVEMENT

Patients with KTS can have macrocephaly and, less frequently, microcephaly. Intracranial angiomas, arteriovenous malformations, and intraspinal angiomas have been described. More than 40 cases of KTS have been described in association with Sturge-Weber syndrome(9).
Ophthalmologic findings reported in association with KTS include: conjunctival telangiectasia, retinal varicosities, choroidal angioma, glaucoma, coloboma iridis, heterochromia iridis, intraorbital varix, and enophthalmos(1,10).

ADDITIONAL FINDINGS AND PROBLEMS
COAGULOPATHY

Some patients with KTS exhibit evidence of an intravascular coagulopathy. This usually is mild but in some patients can be relatively severe and result in bleeding after minor trauma or major bleeding associated with surgical procedures. This coagulopathy probably represents a form of Kasabach-Merritt syndrome and may be manifest by thrombocytopenia, reduced fibrinogen, and the presence of fibrin split products(11). It is prudent to assess patients' coagulation status prior to planned surgical procedures.

PULMONARY EMBOLI

There have been several instances of fatal and nonfatal pulmonary emboli in patients with KTS. It is unclear at this point, which patients with KTS are at risk for this complication. Some episodes have been associated with bed rest following a surgical procedure. One author has recommended that patients with KTS receive anticoagulation therapy when admitted to a hospital or, long-term anticoagulation therapy for those who have had a documented thrombotic event (7).

SYNCOPE

Patients with large venous capacitance in the legs can be prone to lightheadedness and syncope when standing.

MANAGEMENT ISSUES
COMPRESSION THERAPY

Most patients with lower extremity involvement experience some degree of lower extremity edema. This usually is not manifest until after the child begins walking and gravitational forces become a factor. It is important to remember that an extremity may be enlarged because of increased bony and soft tissue mass as well as edema. Compression of the extremity with elastic support will acutely lessen the edema but there is no data that chronic compressive therapy will result ultimately in less bony or soft tissue mass. Also, compression will not affect the ultimate length of the leg. Patients with a major component of lymphedema and those with severe venous insufficiency seem to derive the most benefit from chronic compressive therapy. Compressive therapy also should be used for patients with edema and recurrent cellulitis. It may reduce the frequency of episodes of cellulitis. Compression may or may not be useful for patients with friable skin lesions that tend to bleed. In some cases the compression garment will protect the sites and lessen the bleeding but in other cases, the garment may irritate the skin and increase the bleeding episodes. Compression therapy may slow the progression of lower extremity varicose veins. Compression therapy also is useful for patients with upper extremity involvement who have problems with edema.

We do not favor compression therapy for young children. In general young children will not tolerate wearing a compression garment, they will rapidly outgrow the garment and the parents will just become frustrated. In general a compression garment should extend from the tip of the toes to well above the involved site.

REMOVAL OF VARICOSE VEINS

Unsightly or painful superficial varicose veins can be removed in selected patients. It is critical that the status and integrity of the deep venous system be established before superficial veins are removed. If the deep venous system is inadequate, the superficial veins should not be removed.

EPIPHYSIODESIS

Epiphysiodeses are done to assure relatively equal leg lengths at full maturation. This procedure is necessary only if the projected limb length discrepancy exceeds 2.0 cm. It is important that this operation be done at the appropriate time. Parents need to be reassured that the operation need not be done during early childhood. Most epiphysiodeses are done between 10 and 14 years of age. For limb length discrepancies less that 2.0 cm, shoe lifts can be used.
Intentional destruction of growth plates also can be done to control excessive growth of digits.

AMPUTATION AND RAY RESECTION

Amputation of digits, and portions of an extremity should only be undertaken to improve function of the extremity and to manage otherwise uncontrollable infection or bleeding. Many of these children manage to obtain excellent function from an extremity that is quite enlarged and malformed. An important dictum in managing these patients is to operate to improve function rather than for cosmesis and never to sacrifice function to obtain improved cosmesis. Patients with discordant foot size may have difficulty fitting the foot into a shoe. We have found that ray resection is a very satisfactory procedure to reduce excessive foot width

DEBULKING PROCEDURES

The potential complications of debulking procedures should be considered carefully before undertaking this type of treatment. The potential drawbacks of debulking procedures include: 1. the bulk can return, 2. the bulk is traded for a scar, 3. the debulking procedure may interrupt the venous and lymphatic drainage in an extremity with compromised drainage to begin with , 4. wound infection, and 5. poor skin healing with resultant chronic lymphatic ooze. In general the more proximal on a extremity a debulking procedure is considered , the greater are the risks for interfering with venous and lymphatic drainage. Conversely, debulking procedures on digits, the hands, and feet are tolerated better than those on more proximal locations. As noted above one must always consider function above form when contemplating surgical procedures for patients with KTS.

LASER THERAPY

Laser therapy can be used to reduce the discoloration of capillary hemangiomas. Before embarking on this treatment it must be remembered that the procedure is painful. Also frequently it is the parent that opts to have the lesion treated but it is the child who must undergo the discomfort. It may preferable to wait until the child is old enough to participate in the decision to have this treatment.

ANTIBIOTICS

Antibiotics are used to treat cellulitis. For patients who have recurrent cellulitis, maintaining the patient on prophylactic antibiotics may be helpful.

GASTROINTESTINAL BLEEDING

Gastrointestinal bleeding can occur in patients with perirectal or pericolonic varicose veins. Bleeding can range from minimal to life threatening. As with all cases of GI bleeding the source of bleeding needs to be defined. If the bleeding is secondary to varicose veins and is not life threatening, treatment should consist of stool softeners and iron replacement. Surgery may be necessary to deal with massive recurrent bleeding.

REFERENCES
1. STICKLER, G. KLIPPEL-TRENAUNAY SYNDROME, IN NEUROCUTANEOUS
DISEASES, A PRACTICAL APPROACH GOMEZ, M.,ED ,
BUTTERWORTHS, BOSTON, 1987.

2. BASKERVILLE, P., ACKROYD, J., BROWSE, N., THE ETIOLOGY OF THE KLIPPEL-
TRENAUNAY SYNDROME, ANNALS OF SURGERY,202:624-627,1985

3. AELVOET,G, JORENS, P., ROELEN, L., GENETIC ASPECTS OF THE KLIPPELL-
TRENAUNAY SYNDROME, BRITISH JOURNAL OF DERMATOLOGY, 126:603-
607,1992

4. JORGENSON, R., DARBY, B., PATTERSON, R., TRIMMER,K., PRENATAL
DIAGNOSIS OF THE KLIPPEL-TRENAUNAY-WEBER SYNDROME, PRENATAL
DIAGNOSIS, 14:989-992,1994

5. HAPPLE, R., LETHAL HENES SURVIVING BY MOSAICISM: A POSSIBLE
EXPLANATION FOR SPORADIC BIRTH DEFECTS INVOLVING THE SKIN, JOURNAL
OF THE AMERICAN ACADEMY OF DERMATOLOGY, 16:899- 906,1987.

6. GLOVICZKI, P., STANSON, A., STICKLER, G., JOHNSON, C., TOOMEY, B.,
MELAND, N., ROOKE, T., CHERRY, K., KLIPPEL-TRENAUNAY SYNDROME:
THE RISKS AND BENEFITS OF VASCULAR INTERVENTIONS, SURGERY,
110:469-479.

7. KLIPPEL-TRENAUNAY SYNDROME IN DISEASES OF THE VEINS, PATHOLOGY,
DIAGNOSIS AND TREATMENT, BROWSE, N., BURNAND, K., THOMAS, M.,
ED, EDWARD ARNOLD, BALTIMORE, 1988

8. STEWART, G., FARMER,G., STURGE-WEBER AND KLIPPEL TRENAUNAY
SYNDROMES WITH ABSENCE OF INFERIOR VENA CAVA, ARCH DISEASE
CHILDHOOD(ENGLAND) 65:546-547, 1990.

9. DEUTSCH, J., WEISSENBACHER, G., ET AL, COMBINATION OF THE SYNDROME
OF STURGE-WEBER AND THE SYNDROME OF KLIPPELL-TRENAUNAY, KLIN
PAEDIATR, 188:464-471,1976.

10. BROD, R., SHIELDS, J., SHIELDS, C., OBERKIRCHER, O., SABOL, L., UNUSUAL
RETINAL AND RENAL VASCULAR LESIONS IN THE KLIPPEL-TRENAUNAY-
WEBER SYNDROME, RETINA, 12:355-358, 1992

11. D'AMICO, J., HOFFMAN, GL., DYMENT, PL., KLIPPEL-TRENAUNAY
COAGULATION AND MASSIVE OSTEOLYSIS, CLEVELAND CLINIC
QUARTERLY, 44:181-188, 1977

Table 1. Anatomic involvement in 144 patients with KTS

(adapted from Gloviczki et al, Ref #4)

Patients
Location n %

Lower extremity 132 92
Unilateral 103 72
Right 53 37
Left 50 35
Bilateral 29 21
Lower extremity only 106 74
Lower and upper extremities 26 18
Upper extremity 37 26
Upper extremity only 11 8
Pelvis or abdomen 21 15
Thorax 25 17
Head and neck 7 5

Table 2. Signs and symptoms in 144 patients with KTS

(adapted from Gloviczki et al, Ref #4)

Patients
Location n %

Varicosity 110 76
Atypical (lateral) 66 46
Suprapubic 2 1
Usual distribution 46 32
Hemangioma 137 95
Capillary 89 62
Lymphangioma 12 8
Limb Hypertrophy 134 93
Longer extremity 96 66
Swollen extremity 100 69
Pain 46 32
Cosmetic problem only 35 24
Bleeding from hemangioma 28 19
Thrombophlebitis 18 12
Cellulitis 13 9
Ulcers 11 8
Verrucae 9 6
Rectal Bleeding 14 10
Macroscopic hematuria 4 3
Paraparesis 4 3
Deep venous thrombosis 6 4
Pulmonary embolization 4