The majority of KTWS cases manifest in infancy or childhood [1]. This rare disorder is characterized by the clinical triad of port-wine stain, varicose veins, and hypertrophy of bone and soft tissue, although not all may be present [2]. It typically involves a unilateral extremity, in which the leg is the most frequently affected site [3]. The arms and trunk may be affected as well. Occasionally, multiple limbs are involved.

The port-wine stain, or capillary hemangioma, is the initial sign. It appears as a sharp border on the lateral portion of the limb(s). The hemangioma may be confined to the skin or advanced to the bone and muscle [4], and organs such as the liver, spleen, bladder, large bowel, and others. Hence, vascular malformations that arise in the gastrointestinal (GI) and genitourinary (GU) tracts can cause hematuria, hematochezia, and genital bleeding [5] [6].

Varicosities, which may be apparent at birth, involve a superficial or deep vein of the foot or leg and distribute into the thigh or gluteal region. These may gradually grow in size. Varicose veins produce pain and lymphedema [4], which become worse during pregnancy [7].

The hemihypertrophy stems from the increased bone length and/or the enlarged soft tissue [4]. This is seen at birth and continues to progress during childhood.

Complications

KTWS is associated with severe consequences such as pulmonary embolism [8], thrombophlebitis, coagulopathy, GI and/or GU bleeding [5], and other life-threatening sequelae.

Patients are at risk for developing seizures and various brain pathologies, of which hemimegalencephaly is the most common [9]. Other complications include but are not limited to stroke, arteriovenous malformation, venous malformation, aneurysm, and hydrocephalus.

Physical exam

Remarkable findings include skin lesions described as nevus flammeus, which are pink to purplish in color. Limb asymmetry is typically apparent [9].

• Respiratory Distress

  A newborn female with respiratory distress from birth, and having vascular malformation involving left thigh. The neonate also had hydronephrosis and developed complication of Kasabach Merritt syndrome. [ncbi.nlm.nih.gov]

• Pelvic Mass

  Three patients had an association of pelvic and genital malformations, including 2 patients with hematuria due to vesical lesions and 1 patient with left ureterohydronephrosis due to a pelvic mass. Two patients had urethral lesions. [ncbi.nlm.nih.gov]

  A laparoscopy was performed simultaneously to evaluate the pelvic mass, which was shown to extensively involve the bladder and rectum-sigmoid colon, and was considered irresectable. [scielo.br]

• Cardiomegaly

  The sonographic appearance of this disorder was characterized by the presence of multiple distorted cystic areas involving the right leg and abdomen and cardiomegaly with early fetal heart failure. [ncbi.nlm.nih.gov]

  However, ascites increased gradually and clinical signs of fetal cardiac failure as evidenced by cardiomegaly (cardiothoracic dimension ratio of 45%) and increased skin edema that had once decreased after thoracoamniotic shunting necessitated a cesarean [degruyter.com]

  The patient's medications consisted of lisinopril for mild hypertension and cardiomegaly. He had no known drug allergies. Socially, the patient denied alcohol or tobacco abuse. [omicsonline.org]

• Gingival Hypertrophy

  The most striking oral feature was generalized severe gingival hypertrophy confirmed histologically, ultrastructurally, and by collagen analysis. [ncbi.nlm.nih.gov]

• Upper Back Pain

  A 23-year-old woman was admitted to our institution with acute onset of leg weakness accompanied by upper back pain. Thoracic magnetic resonance imaging of the spinal cord showed a heterogeneous mass with a slit component at the T1-2 level. [ncbi.nlm.nih.gov]

• Angiokeratoma

  Skin examination showed numerous angiokeratoma, which had developed only on the right part of the body, with a sharp delineation in the midline of the trunk. [ncbi.nlm.nih.gov]

• Aggressive Behavior

  Angiosarcomas are neoplasms of blood or lymphatic vessels with aggressive behavior. [ncbi.nlm.nih.gov]

• Cryptorchidism

  The clinical presentation included genital deformities in 3 cases, hematuria in 2 and urethrorragia in 2, one of which associated with cryptorchidism and phimosis. [ncbi.nlm.nih.gov]

• Urethral Discharge

  At a 4-month follow-up, the patient only had slightly bloodstained urethral discharge, and is doing well. This is the first case reporting endoscopic sclerotherapy for a KTS-associated urethral hemangioma. [ncbi.nlm.nih.gov]

• Unable to Walk

  His symptoms had progressed to the point that he was unable to walk. [ncbi.nlm.nih.gov]

The clinical assessment consists of the patient history, a physical exam, and possibly imaging studies.

Imaging

Ultrasonography with color doppler is effective in diagnosing the condition [10]. Additionally, duplex scanning contrast venography and contrast arteriography are among the imaging modalities that assess the circulatory system while magnetic resonance angiography (MRA) identifies vascular malformations. Also, magnetic resonance imaging (MRI) evaluates the soft tissue hypertrophy.

Preoperative planning can be conducted with multidetector computed tomography (MDCT) and 3-dimensional MRI venography, which provide details about soft tissue, bone, and both superficial and deep venous circulation [11]. More recently, experts have advocated for the use of MDCT arteriography to assist with planning [12].

Skeletal radiographs, scanograms, and CT scans are used to determine the limb-length discrepancy. Tracking the progress of bone growth offers information that helps with optimizing the timing of surgical intervention.

CT imaging of the abdomen and pelvis [13], ultrasonography, and colonoscopy [14] are performed to evaluate GI and GU bleeding.

Prenatal tests

Routine and widespread use of prenatal ultrasonography can detect limb hypertrophy and asymmetry, venous malformation, subcutaneous cystic masses, and other abnormalities in the developing fetus [15]. These findings warrant further testing with chromosomal analysis.

1. Kihiczak GG, Meine JG, Schwartz RA, Janniger CK. Klippel-Trenaunay syndrome: a multisystem disorder possibly resulting from a pathogenic gene for vascular and tissue overgrowth. Int J Dermatol. 2006; 45(8):883- 90.
2. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P. Klippel-Trénaunay syndrome: Spectrum and management. Mayo Clin Proc. 1998;73(1):28–36.
3. Dohil MA, Baugh WP, Eichenfield LF. Vascular and pigmented birthmarks. Pediatr Clin North Am. 2000;47(4):783-812, v-vi.
4. Cebeci E, Demir S, Gursu M, et al. A Case of Newly Diagnosed Klippel Trenaunay Weber Syndrome Presenting with Nephrotic Syndrome. Case Rep Nephrol. 2015;2015:704379.
5. Samuel M, Spitz L. Klippel-Trenaunay syndrome: clinical features, complications and management in children. Br J Surg. 1995;82(6):757-61.
6. Timur AA, Driscoll DJ, Wang Q. Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis. Cell Mol Life Sci. 2005;62(13):1434-1447.
7. Andreasen KR, Tabor A, Weber T. Klippel–Trenaunay–Weber syndrome in pregnancy and at delivery. J Obstet Gynaecol. 1999;19(1):78-9.
8. Pedersen RS, Hedelund L, Poulsen LH, Bach A, Keller J. Ugeskr Laeger. Fatal Klippel-Trénaunay syndrome in a child with pulmonary embolism.2013;175(38):2183-4.
9. Ricks CB, Grandhi R, Ducruet AF. Klippel-Trenaunay syndrome and cavernous malformations. BMJ Case Rep. 2014;2014. pii: bcr2014207486.
10. Qi HT, Wang XM, Zhang XD, et al. The role of colour Doppler sonography in the diagnosis of lower limb Klippel-Trénaunay syndrome. Clin Radiol. 2013; 68(7):716-20.
11. Bastarrika G, Redondo P, Sierra A, et al. New techniques for the evaluation and therapeutic planning of patients with Klippel-Trénaunay syndrome. J Am Acad Dermatol. 2007;56(2):242-9.
12. Li X, Tian J. Multidetector row computed tomography arteriography in the preoperative assessment of patients with Klippel-Trénaunay syndrome. J Am Acad Dermatol. 2009; 60(2):345-6; author reply 346.
13. Yeoman LJ, Shaw D. Computerized tomography appearances of pelvic haemangioma involving the large bowel in childhood. Pediatr Radiol. 1989;19(6-7):414-6.
14. Wang Z-K, Wang F-Y, Zhu R-M, Liu J. Klippel-Trenaunay syndrome with gastrointestinal bleeding, splenic hemangiomas and left inferior vena cava. World J Gastroenterol. 2010; 28;16(12):1548-52.
15. Cakiroglu Y, Doğer E, Yildirim Kopuk S, Dogan Y, Calıskan E, Yucesoy G. Sonographic Identification of Klippel-Trenaunay-Weber Syndrome. Case Rep Obstet Gynecol. 2013;2013:595476.