THE SYNDROME PAGE Pediatric Dermatology Vol. 9 No. 1 80-82
Editors: Susan B. MaUory, M.D., and Bernice R. Krafchik, M.B., Ch.B., F.R.C.P.(C)
What Syndrome Is This?
Figure 1. Patient 1 had bilateral involvement of the lower extremities. Note edema of the dorsa of the feet.
Figure 2. Patient 1. Capiliary malformation with distinct border. Address correspondence to Susan B. Mallory, M.D.. Dermatology Division. St. Louis Children's Hojipital. 400 S. Kingshighway. St. Louis. MO 63i 10. No reprints available.
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The Syndrome Page 81
Klippel-Trenaenay Syndrome
Figure 3. In patient 2, deep vessels are involved, causing overgrowth of soft tissue in the affected arm and anterior chest.
Figure 4. Patient 2. Overgrowth of soft tissue of the right hand compared with the left. Note capillary malformation, Which has distinct border across the dorsum of the hand.
Naevus vasculosus osteohypertrophicus, better known as Klippel-Trenaunay syndrome (KTS), was named after the investigators who first described the condition in 1900. These men identified a characteristic triad of nevus flammetis. varicosities, and bone and soft tissue hypertrophy of the involved extremity (1). In 1918 Weber added arteriovenous fistula to the triad, further delineating the KlippelTrenaunay-Weber syndrome (2). Klippei-Trenaunay syndrome is a rare disorder that affects significantly more males than females. Although familial inheritance has been identified (3). patients usually exhibit at least one of the characteristic clinical signs at birth or soon thereafter (4). Neither gestational events nor teratogen exposure has been shown to cause this syndrome (3). The etiology of KTS remains tinknown, but many theories have been proposed. One suggests blockage of the deep or superficial veins of the leg from agenesis, atresia. or external compression by abnormal muscles, fibrous bands, or perivenous sheaths (5). Another theory proposes that altered angiogenesis arising from a mesodermal defect could result in the absence of venular valves, leading to reflux in the superficial and deep venous systems and resulting in chronic venous hypertension (5). This increase in blood flow could explain the bone and soft tissue hypertrophy (6); however, the extent of this hypertrophy is not necessarily proportional to the increase in blood flow (7). Still another theory implicates abnormal development in embryologic vascular maturation. Findings might include remnant fetal capillaries evident as cutaneous vascular malformations, remnant arteriovenous connections with obvious clinical importance, aplasia of some vessels or persistence of others, or concomitant lymphatic malformations. Each of these early developmental abnormalities has serious consequences for later development that rnay manifest clinically as KTS (8). The typical syndrome appears as a triad of clinical manifestations. The first sign, a capillary malformation, has a distinct, linear border that often stops at the midline. It usually overlies deeper vascular malformations and affects only the involved extremity, but is sometimes present on other extremities as well (5). Second, congenital varicose veins are usually seen on the outer side of the leg (4). The third finding is bone and soft tissue hypertrophy
82 Pediatric Dermatology Vol. 9 No. 1 March 1992
with resulting enlargement and elongation of the involved extremity. Occasionally, the involved extremity may be atrophic instead of hypertrophied (4,9). Other anomalies have been described in association with this triad: lymphatic obstruction (5), spina bifida, hypospadias, polydactyly, and syndactyly (3). If present, chronic venous insufficiency may cause cutaneous changes such as edema, stasis changes, hyperpigmentation, poor healing, and ulceration (6). Thrombosis may occur in the deep and superficial systems and may rarely be associated with pulmonary embolism (10). Laboratory investigations may reveal several relevant findings. Radiologically, arteries appear normal, but the venous system may show superficial varicosities, signs of reflux, or possibly absence of popliteal, femoral, or external iliac veins (11). One study demonstrated that the blood flow in the affected calf was greater in the abnormal limb than in the normal limb, and that this was related to the presence of blood flow through the cutaneous capillary malformations (7). Microscopically, they demonstrated hypertrophy of the smooth muscle in the walls of the subcutaneous veins, suggesting chronically increased blood flow (7). Treatment of KTS is conservative and symptomatic. Compressive stockings may be helpful if edema is present. Similarly, a lymphedema pump may be useful for severe refractory edema. Lymphedema may be aggravated by stripping varicose veins (9) and thus should be avoided. However, with the use of radiographic studies, identification of surgically correctable lesions such as hypoplasia or aplasia (5,11) may be achieved. The presence of arteriovenous fistulae distinguishes between KTS, which lacks this feature, and Klippel-Trenaunay-Weber syndrome (KTWS), in which fistulae are present (1,2). Klippel-Trenaunay syndrome affects the lower extremities in up to 95% of patients, with 12.5% having bilateral involvement (3). Patients can be classified into three groups based on the presence or absence of deep venous anomalies and/or arteriovenous fistulae (10). Less common than KTS, KTWS differs in several ways. The former generally has deep and lateral venous anomalies and disproportionate extremity hypertrophy, whereas KTWS lacks both features. In addition, bone and soft tissue hypertrophy in KTWS tends to be progressive because of the arteriove-
nous fistula. Patients with KTS have a better prognosis than those with KTWS, who may develop congestive heart failure due to the increased cardiac output associated with an arteriovenous fistula. In KTS the cutaneous vascular malformation may undergo thrombosis, leading to slow regression of the cutaneous lesion (10). ACKNOWLEDGMENT
The cost of color illustrations for this section of the journal is underwritten by Westwood Pharmaceuticals, Inc. Daniel S. Ring, B.A. Susan B. Mallory, M.D.
Division of Dermatology Washington University School of Medicine St. Louis, Missouri REFERENCES 1. Klippel M, Trenaunay P. Naevus Variqueux osteohypertrophique. J Practiciens 19O0;14:65-70. 2. Parkes Weber F. Haemangiectatic hypertrophy of limbs—congenital phlebarteriectasis and so-called congenital varicose veins. Br J Child Dis J918:!5:1317. 3. Gloviczki P, Hollier LM, Telander RL, Kaufman B. Surgical implications of Klippel-Trenaunay syndrome. Ann Surg 1983;197:353-362. 4. Lindenauer SM. The Klippel-Trenaunay syndrome. Ann Surg 1965;162:303-314. 5. Servelle M. Klippel and Trenaunay's syndrome. Ann Surg]985;201:365-373. 6. Muilins FJ, Naylor D, Redetski H. The KlippelTrenaunay-Weber syndrome. Arch Dermatol 1962; 86:202-206. 7. Baskerville PA, Ackroyd JS, Browse NL. The etiology of the Klippel-Trenaunay syndrome. Ann Surg 1985;202:624-627. 8. Young AE. Pathogenesis of vascular malformations. In: MuUiken JB, Young AE, eds. Vascular birthmarks: hemangiomas and malformations. Philadelphia: WB Saunders, 1988:107-113. 9. Young AE. Congenital mixed vascular deformities of the limbs and their associated lesions. Birth Defects 1978;14(6B):289-296. 10. Young AE. Combined vascular malformations. In: MuUiken JB, Young AE, eds. Vascular birthmarks: hemangiomas and malformations. Philadelphia: WB Saunders, 1988:246-274. 11. Mahmoud SF, El-Benhawi MO, El-Tonsy MH, Kalantar SM. Klippel-Trenaunay syndrome. J Am Acad Dermatol 1988,18:1169^1172.
Editors: Susan B. MaUory, M.D., and Bernice R. Krafchik, M.B., Ch.B., F.R.C.P.(C)
What Syndrome Is This?
Figure 1. Patient 1 had bilateral involvement of the lower extremities. Note edema of the dorsa of the feet.
Figure 2. Patient 1. Capiliary malformation with distinct border. Address correspondence to Susan B. Mallory, M.D.. Dermatology Division. St. Louis Children's Hojipital. 400 S. Kingshighway. St. Louis. MO 63i 10. No reprints available.
80
The Syndrome Page 81
Klippel-Trenaenay Syndrome
Figure 3. In patient 2, deep vessels are involved, causing overgrowth of soft tissue in the affected arm and anterior chest.
Figure 4. Patient 2. Overgrowth of soft tissue of the right hand compared with the left. Note capillary malformation, Which has distinct border across the dorsum of the hand.
Naevus vasculosus osteohypertrophicus, better known as Klippel-Trenaunay syndrome (KTS), was named after the investigators who first described the condition in 1900. These men identified a characteristic triad of nevus flammetis. varicosities, and bone and soft tissue hypertrophy of the involved extremity (1). In 1918 Weber added arteriovenous fistula to the triad, further delineating the KlippelTrenaunay-Weber syndrome (2). Klippei-Trenaunay syndrome is a rare disorder that affects significantly more males than females. Although familial inheritance has been identified (3). patients usually exhibit at least one of the characteristic clinical signs at birth or soon thereafter (4). Neither gestational events nor teratogen exposure has been shown to cause this syndrome (3). The etiology of KTS remains tinknown, but many theories have been proposed. One suggests blockage of the deep or superficial veins of the leg from agenesis, atresia. or external compression by abnormal muscles, fibrous bands, or perivenous sheaths (5). Another theory proposes that altered angiogenesis arising from a mesodermal defect could result in the absence of venular valves, leading to reflux in the superficial and deep venous systems and resulting in chronic venous hypertension (5). This increase in blood flow could explain the bone and soft tissue hypertrophy (6); however, the extent of this hypertrophy is not necessarily proportional to the increase in blood flow (7). Still another theory implicates abnormal development in embryologic vascular maturation. Findings might include remnant fetal capillaries evident as cutaneous vascular malformations, remnant arteriovenous connections with obvious clinical importance, aplasia of some vessels or persistence of others, or concomitant lymphatic malformations. Each of these early developmental abnormalities has serious consequences for later development that rnay manifest clinically as KTS (8). The typical syndrome appears as a triad of clinical manifestations. The first sign, a capillary malformation, has a distinct, linear border that often stops at the midline. It usually overlies deeper vascular malformations and affects only the involved extremity, but is sometimes present on other extremities as well (5). Second, congenital varicose veins are usually seen on the outer side of the leg (4). The third finding is bone and soft tissue hypertrophy
82 Pediatric Dermatology Vol. 9 No. 1 March 1992
with resulting enlargement and elongation of the involved extremity. Occasionally, the involved extremity may be atrophic instead of hypertrophied (4,9). Other anomalies have been described in association with this triad: lymphatic obstruction (5), spina bifida, hypospadias, polydactyly, and syndactyly (3). If present, chronic venous insufficiency may cause cutaneous changes such as edema, stasis changes, hyperpigmentation, poor healing, and ulceration (6). Thrombosis may occur in the deep and superficial systems and may rarely be associated with pulmonary embolism (10). Laboratory investigations may reveal several relevant findings. Radiologically, arteries appear normal, but the venous system may show superficial varicosities, signs of reflux, or possibly absence of popliteal, femoral, or external iliac veins (11). One study demonstrated that the blood flow in the affected calf was greater in the abnormal limb than in the normal limb, and that this was related to the presence of blood flow through the cutaneous capillary malformations (7). Microscopically, they demonstrated hypertrophy of the smooth muscle in the walls of the subcutaneous veins, suggesting chronically increased blood flow (7). Treatment of KTS is conservative and symptomatic. Compressive stockings may be helpful if edema is present. Similarly, a lymphedema pump may be useful for severe refractory edema. Lymphedema may be aggravated by stripping varicose veins (9) and thus should be avoided. However, with the use of radiographic studies, identification of surgically correctable lesions such as hypoplasia or aplasia (5,11) may be achieved. The presence of arteriovenous fistulae distinguishes between KTS, which lacks this feature, and Klippel-Trenaunay-Weber syndrome (KTWS), in which fistulae are present (1,2). Klippel-Trenaunay syndrome affects the lower extremities in up to 95% of patients, with 12.5% having bilateral involvement (3). Patients can be classified into three groups based on the presence or absence of deep venous anomalies and/or arteriovenous fistulae (10). Less common than KTS, KTWS differs in several ways. The former generally has deep and lateral venous anomalies and disproportionate extremity hypertrophy, whereas KTWS lacks both features. In addition, bone and soft tissue hypertrophy in KTWS tends to be progressive because of the arteriove-
nous fistula. Patients with KTS have a better prognosis than those with KTWS, who may develop congestive heart failure due to the increased cardiac output associated with an arteriovenous fistula. In KTS the cutaneous vascular malformation may undergo thrombosis, leading to slow regression of the cutaneous lesion (10). ACKNOWLEDGMENT
The cost of color illustrations for this section of the journal is underwritten by Westwood Pharmaceuticals, Inc. Daniel S. Ring, B.A. Susan B. Mallory, M.D.
Division of Dermatology Washington University School of Medicine St. Louis, Missouri REFERENCES 1. Klippel M, Trenaunay P. Naevus Variqueux osteohypertrophique. J Practiciens 19O0;14:65-70. 2. Parkes Weber F. Haemangiectatic hypertrophy of limbs—congenital phlebarteriectasis and so-called congenital varicose veins. Br J Child Dis J918:!5:1317. 3. Gloviczki P, Hollier LM, Telander RL, Kaufman B. Surgical implications of Klippel-Trenaunay syndrome. Ann Surg 1983;197:353-362. 4. Lindenauer SM. The Klippel-Trenaunay syndrome. Ann Surg 1965;162:303-314. 5. Servelle M. Klippel and Trenaunay's syndrome. Ann Surg]985;201:365-373. 6. Muilins FJ, Naylor D, Redetski H. The KlippelTrenaunay-Weber syndrome. Arch Dermatol 1962; 86:202-206. 7. Baskerville PA, Ackroyd JS, Browse NL. The etiology of the Klippel-Trenaunay syndrome. Ann Surg 1985;202:624-627. 8. Young AE. Pathogenesis of vascular malformations. In: MuUiken JB, Young AE, eds. Vascular birthmarks: hemangiomas and malformations. Philadelphia: WB Saunders, 1988:107-113. 9. Young AE. Congenital mixed vascular deformities of the limbs and their associated lesions. Birth Defects 1978;14(6B):289-296. 10. Young AE. Combined vascular malformations. In: MuUiken JB, Young AE, eds. Vascular birthmarks: hemangiomas and malformations. Philadelphia: WB Saunders, 1988:246-274. 11. Mahmoud SF, El-Benhawi MO, El-Tonsy MH, Kalantar SM. Klippel-Trenaunay syndrome. J Am Acad Dermatol 1988,18:1169^1172.
