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Synonyms: Klippel-Trénaunay-Weber syndrome, angio-osteohypertrophy syndrome, naevus vasculosus osteohypertrophicus
Note: the term Klippel-Trénaunay-Weber syndrome has been variably used with different meanings:
- Synonymously with Klippel-Trénaunay syndrome.
- As a separate condition, also known as Parkes Weber's syndrome (limb enlargement with a high-flow capillary malformation and arteriovenous fistula).
Current consensus separates the names into Klippel-Trénaunay syndrome and Parkes Weber's syndrome, so as to distinguish between the two conditions. This is clinically relevant because their management and prognosis differ.
Klippel-Trénaunay (KT) syndrome is a rare and sporadic congenital disorder, characterised by the classical triad of:
- Cutaneous capillary malformations - usually port-wine stains.
- Soft tissue and bone hypertrophy (occasionally hypotrophy) - usually of one lower limb.
- Varicose veins and venous malformations.
Varicosities and limb hypertrophy are not always present at birth and may take several years to manifest. Not all cases have the full triad of features.
There is wide variation in the clinical manifestations of the condition. Some patients have complex features, including internal abnormalities.
The affected limb may also have abnormalities of lymphatic channels and drainage, along with arterial malformations. Blood flow through the capillary abnormalities in KT syndrome is low-velocity, in contrast to Parkes Weber's syndrome where there is a true arteriovenous malformation with high-velocity blood flow.
The condition may affect more than one limb, an internal organ or the head and neck. Visceral involvement is thought to be more common than previously supposed, occurring in perhaps 20% of patients.
Causes of Klippel-Trénaunay syndrome (aetiology)
The cause is is unknown. KT syndrome is extremely rare.
How common is Klippel-Trénaunay syndrome? (Epidemiology)
KT syndrome is a rare disease, affecting 1 in 20,000–40,000 children. It affects both sexes equally and is seen in all races. While it mostly occurs sporadically, some inherited cases have been reported.
It is unilateral and mostly affects the lower extremities. It can rarely affect bilateral limbs and the upper extremities. The common symptoms are pain and lymphoedema.
Other symptoms include superficial thrombophlebitis, deep vein thrombosis, pulmonary embolism, bleeding, hypospadias, oligodactyly, paraesthesia, angiosarcoma, ulceration, thrombosis, stasis dermatitis, decalcification of involved bones, poor wound healing, hyperhidrosis, hypertrichosis, and spina bifida.
Cutaneous capillary malformations
- The characteristic capillary haemangioma will be visible from birth in the vast majority of cases (98% in one series).
- The skin lesion has a characteristic 'port-wine stain' appearance, usually red-purple or bluish in colour (in contrast to that of Parkes Weber's syndrome which appears bright red).
By Aamartinez0626 (Own work), CC BY-SA 4.0, via Wikimedia Commons
Venous malformations and varicosities
- These are mostly superficial, but may involve muscle, bone or visceral organs, including the spleen, liver, pleura, bladder or colon.
- They may be extensive in the affected limb.
- They usually manifest when the child starts walking.
- There may be lymphatic hypoplasia or aplasia with resulting lymphoedema. This can complicate the condition and contribute to the limb enlargement.
- Limb lengthening may present initially as gait disturbance.
- Limb hypertrophy is often greater distally. The digits may be affected, with macrodactyly, syndactyly, polydactyly or oligodactyly.
- An increase in limb girth may be the main feature if soft tissues rather than bones are predominantly affected.
- Rarely, the affected limb may show atrophy rather than hypertrophy.
Complications of Klippel-Trénaunay syndrome
- Psychological problems due to cosmetic appearance.
- Chronic venous stasis and its complications:
- Visceral bleeding:[4, 10]
- This ranges from occult to massive and life-threatening.
- It usually presents in childhood.
- The most common sites of gastrointestinal bleeding are the distal colon and rectum. Other sites, such as jejunal vascular malformations and oesophageal varices, are reported.
- Splenic haemangiomas may occur.
- Orthopaedic complications:
- Gait disturbance.
- Chronic pain in the affected limb.
- Haemangiomas of the liver, kidney, heart or lungs have also been reported.
- One reported case involved a cerebral haemangiopericytoma (a malignant vascular tumour).
- Parkes Weber's syndrome (where there is a high-flow arteriovenous malformation rather than capillary haemangioma, as above).
- Other syndromes involving port-wine stains and high-flow shunts - eg, capillary malformation-arteriovenous malformations syndrome, Cobb's syndrome and CLOVES syndromes (Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal naevi and Spinal/scoliosis/seizures/skeletal abnormalities).
- Sturge-Weber syndrome.
- Proteus' syndrome (rare hamartomatous disorder causing asymmetrical hypertrophy of a range of tissues, possibly afflicting Joseph Merrick, the so-called 'Elephant Man').
- Congenital lymphatic atresia or obstruction.
- Maffucci's syndrome (rare dysembryoplasia causing cartilage and vessel tumours).
- Kaposiform haemangioendothelioma.
- Investigation of the vascular or lymphatic malformations - various methods may be used; for example:
- Doppler ultrasound.
- Angiography or MRI/CT angiography.
- MRI or CT.
- CT of the abdomen and pelvis may help to identify visceral haemangiomas.
- Whole-body blood pool scintigraphy.
- Lymphoscintigraphy may be used to assess the lymphatic system and the cause of limb-length discrepancy.
- Imaging of the bone and soft tissues of the affected limb, using plain X-rays, MRI or CT scan.
- If there is gastrointestinal bleeding, it may be difficult to locate the source by endoscopy, since the venous malformations can be widely spread. Angiography can be helpful for both diagnosis and treatment of these lesions and has been used to locate and treat severe bleeding in one reported case.
Management of Klippel-Trénaunay syndrome
There is no curative therapy. Management requires a multidisciplinary and individualised approach.
Symptomatic treatment is used to improve quality of life. Relative indications for intervention include pain, functional impairment, swelling, limb asymmetry, or cosmetic reasons. Absolute indications include haemorrhage, infections, refractory ulcers, or acute thromboembolism.
- Graduated compression garments help to reduce the effect of chronic venous insufficiency in the affected limb. Intermittent pneumatic compression pumps may also be used to the same effect. These help to reduce the effects of venous insufficiency but do not affect the ultimate size of the limb.
- Prophylaxis for VTE may be appropriate.
- Standard treatments for cellulitis or thrombophlebitis.
- Pain management.
- Contraception: oestrogen-containing contraceptives are contra-indicated where there is a history of VTE and should probably be avoided in KT syndrome because of the increased VTE risk (although there is no specific UK contraception guideline for this condition).
- Pregnant women with KT syndrome need careful monitoring due to a range of haematological, obstetric and anaesthetic complications.
- Laser treatment (pulsed dye laser) for cosmetic improvement of head and neck cutaneous lesions.
- Pre-operative assessment:
- Detailed pre-operative assessment of the venous system is important because there may be associated hypoplasia of the deep veins.
- Careful anaesthetic assessment is required, including for possible consumptive coagulopathy.[9, 18]
- Surgery for long bone fractures in the affected limbs is associated with high risk due to increased haemorrhage. This requires careful pre-operative planning, surgical technique and intra-operative/postoperative support.
- Vascular interventions:
- Treatment of the more severe venous malformations may include:
- Sclerotherapy with foam or with alcohol.
- Vascular surgery such as:
- Gastrointestinal bleeds may require angiographic treatment - eg, selective arterial embolisation has been used in one case; or intra-arterial infusion of vasopressin has been suggested. Surgical resection of the bowel may be required.
- For splenic haemangiomas, small ones (<4 cm) have been managed conservatively; splenectomy may be considered for larger lesions.
- Erectile dysfunction has been successfully treated by ligation of the affected veins.
- Orthopaedic interventions:
- Limb length discrepancy may be treated with orthoses or orthopaedic surgery, depending on its severity.
- De-bulking surgery for grossly enlarged limbs is occasionally used but carries a significant risk of lymphatic and venous damage.
- Amputation may be used in cases where a limb or digit is of little functional use and causes severe symptoms or complications.
Life expectancy is largely normal, depending on the severity of the malformation and thus the likelihood of complications.
Further reading and references
Schook CC, Mulliken JB, Fishman SJ, et al; Differential diagnosis of lower extremity enlargement in pediatric patients referred with a diagnosis of lymphedema. Plast Reconstr Surg. 2010 Dec 23.
Klippel-Trenaunay-Weber Syndrome; Online Mendelian Inheritance in Man (OMIM)
Meier S; Klippel-Trenaunay syndrome: a case study. Adv Neonatal Care. 2009 Jun9(3):120-4.
Asghar F, Aqeel R, Farooque U, et al; Presentation and Management of Klippel-Trenaunay Syndrome: A Review of Available Data. Cureus. 2020 May 812(5):e8023. doi: 10.7759/cureus.8023.
Kocaman O, Alponat A, Aygun C, et al; Lower gastrointestinal bleeding, hematuria and splenic hemangiomas in Turk J Gastroenterol. 2009 Mar20(1):62-6.
Sung HM, Chung HY, Lee SJ, et al; Clinical Experience of the Klippel-Trenaunay Syndrome. Arch Plast Surg. 2015 Sep42(5):552-8. doi: 10.5999/aps.2015.42.5.552. Epub 2015 Sep 15.
Klippel–Trénaunay syndrome; DermNet.
Klippel-Trenaunay-Weber Syndrome; Online Mendelian Inheritance in Man (OMIM)
Holak EJ, Pagel PS; Successful use of spinal anesthesia in a patient with severe Klippel-Trenaunay syndrome associated with upper airway abnormalities and chronic Kasabach-Merritt coagulopathy. J Anesth. 2010 Feb24(1):134-8.
Beier UH, Schmidt ML, Hast H, et al; Control of disseminated intravascular coagulation in Klippel-Trenaunay-Weber syndrome using enoxaparin and recombinant activated factor VIIa: a case report. J Med Case Reports. 2010 Mar 194:92.
Wang ZK, Wang FY, Zhu RM, et al; Klippel-Trenaunay syndrome with gastrointestinal bleeding, splenic hemangiomas and left inferior vena cava. World J Gastroenterol. 2010 Mar 2816(12):1548-52.
Agrawal V, Minhas S, Ralph DJ; Venogenic erectile dysfunction in Klippel-Trenaunay syndrome. BJU Int. 2006 Feb97(2):327-8.
Mathews MS, Kim RC, Chang GY, et al; Klippel-Trenaunay syndrome and cerebral haemangiopericytoma: a potential association. Acta Neurochir (Wien). 2008 Apr150(4):399-402
Alomari AI; A truly unusual overgrowth syndrome: an alternative diagnosis to Klippel-Trénaunay-Weber syndrome. Intern Med. 200948(6):493-4
Funayama E, Sasaki S, Oyama A, et al; How do the type and location of a vascular malformation influence growth in Klippel-Trénaunay syndrome? Plast Reconstr Surg. 2011 Jan127(1):340-6.
Mavili E, Ozturk M, Akcali Y, et al; Direct CT venography for evaluation of the lower extremity venous anomalies of Klippel-Trenaunay Syndrome. AJR Am J Roentgenol. 2009 Jun192(6):W311-6.
Gloviczki P, Driscoll DJ; Klippel-Trenaunay syndrome: current management. Phlebology. 200722(6):291-8.
Sivaprakasam MJ, Dolak JA; Anesthetic and obstetric considerations in a parturient with Klippel-Trenaunay syndrome. Can J Anaesth. 2006 May53(5):487-91.
Pereda Marin RM, Garcia Collada JC, Garrote Martinez AI, et al; Anesthetic management of Klippel-Trénaunay syndrome and attendant gastrointestinal hemorrhage. A case report. Minerva Anestesiol. 2007 Mar73(3):187-90. Epub 2006 Dec 12.
Tsaridis E, Papasoulis E, Manidakis N, et al; Management of a femoral diaphyseal fracture in a patient with Klippel-Trenaunay-Weber syndrome: a case report. Cases J. 2009 Aug 262:8852.
Parashette KR, Cuffari C; Sclerotherapy of rectal hemangiomas in a child with Klippel-Trenaunay-Weber syndrome. J Pediatr Gastroenterol Nutr. 2011 Jan52(1):111-2.