Klippel-Trenaunay-Weber syndrome

Synonyms: KTW syndrome, Klippel-Trenaunay syndrome, angio-osteohypertrophy syndrome, naevus vasculosus osteohypertrophicus

See also: Sturge-Weber syndrome.

This is unknown, though several theories exist. Damage or malformation of the sympathetic ganglia in-utero, damage to deep veins leading to venous hypertension or mesodermal maldevelopment causing the formation of microscopic arteriovenous communications have all been suggested.²

The condition appears to be sporadic but there are families in whom the condition may be inherited in an autosomal dominant fashion with marked variation in penetrance. An abnormality in a gene locus on the long arm of chromosome 5 appears to be involved.³

This is a rare sporadic condition and there are no available figures for its annual incidence or prevalence in the population.

Vascular malformations

• The characteristic capillary haemangioma will be visible from birth in the vast majority of cases (98% in one series).³
• The skin lesion has a characteristic 'port-wine stain' appearance, being deep-purple in colour (in contrast to that of Parkes-Weber syndrome which appears bright red), with clear demarcation from normal skin.
  
  
• Abnormal veins and marked varicosities may be present.
• Lymphoedema may complicate the condition and contribute to the limb enlargement.

Limb abnormalities

• Limb hypertrophy may begin by affecting the digits only and cause macrodactyly, syndactyly, polydactyly or oligodactyly.
• An increase in limb girth may be the only feature where soft tissues rather than bones are predominantly affected.
• Limb-lengthening may present initially as gait disturbance.
• Rarely, the affected limb may show atrophy rather than hypertrophy.

Other problems

• If the cutaneous haemangioma is large it may cause a consumptive coagulopathy known as Kasabach-Merritt syndrome typified by anaemia, thrombocytopenia, prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), reduced fibrinogen levels, and elevation of fibrin degradation products.
• Pulmonary or venous thromboembolism may occur rarely as part of the Kasabach-Merritt syndrome.
• If the head is affected then the syndrome may cause macrocephaly and/or learning difficulties.
• Other features include:²
  • Spina bifida
  • Hypospadias
  • Hyperhidrosis
  • Hypertrichosis
  • Paraesthesiae
  • Decalcification of affected bones
  • Chronic venous insufficiency
  • Stasis dermatitis
  • Poor wound healing
  • Venous ulceration
  There has also been a reported case of portosystemic encephalopathy⁴ and a cerebral haemangiopericytoma.⁵

• Parkes-Weber syndrome (where there is a high-flow arteriovenous malformation rather than capillary haemangioma)
• Sturge-Weber syndrome (facial port-wine stain, epilepsy and hemiparesis)
• Maffuci syndrome (rare dysembryoplasia causing cartilage and vessel tumors)
• 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
• Kaposiform hemangioendothelioma

Imaging of the deep venous systems must be carried out before any vascular interventions,¹ most often using magnetic resonance imaging in a modern setting. Arteriography or duplex ultrasound scanning may be used to investigate the possibility of an arteriovenous malformation. CT scanning may be used to determine exact limb-length discrepancy as a prelude to any corrective surgery. Lymphoscintigraphy may be used to assess the lymphatic system and the cause of limb-length discrepancy.⁶

There is no curative therapy and management aims to ameliorate the patient's symptoms and correct the consequences of limb-length discrepancy.¹

Conservative measures

• 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.
• Cellulitis and thrombophlebitis can be managed with antibiotics, limb elevation, analgesia and corticosteroids. Prophylactic aspirin ± anticoagulants may be used in those who have recurrent thrombophlebitis or before surgery/during pregnancy.
• The United Kingdom Medical Eligibility Criteria for Contraceptive Use (UKMEC) does not give any specific recommendations for women with KTW syndrome but no other complications. However, it does specify that where there has been a history of venous thromboembolism (VTE), progestogen-only pills, implants or injectables, a copper-bearing intrauterine device or a levonorgestrel-releasing intrauterine system are suggested options. Where there is ongoing VTE and is on anticoagulants, progestogen-only pills or barrier methods are preferred.⁷
• Pregnant women with KTW syndrome need careful monitoring due to a range of haematological, obstetric and anaesthetic complications.⁸

Active/surgical measures

• Laser therapy can be used to lessen the cosmetic effect of the cutaneous stain.
• Vascular interventions to treat more severe venous malformations may include sclerotherapy with alcohol or foam, endovenous thermal ablation or surgical stripping and phlebectomy.¹ However, there is some controversy surrounding their long-term outcomes.
• 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 the limb is of little functional use and causes severe complications.

• Psychological problems due to cosmetic appearance
• Skin bleeding
• Venous ulceration
• Chronic venous dermatitis
• Secondary skin infection
• Chronic paraesthesiae
• Pulmonary or venous thromboembolic disease
• Kasabach-Merritt syndrome (see presentation section above)
• Thrombophlebitis
• Cellulitis
• Scoliosis
• Gait disturbance
• Erectile dysfunction in men due to disturbance of venous function⁹
• Chronic pain in the affected limb

Life expectancy is largely normal, depending on the severity of the malformation and thus the likelihood of complications. About 10% of patients are affected by pulmonary embolism.⁶ There may be significant morbidity associated with the condition but most patients do well with conservative therapy and lead relatively normal lives. Amputation is rarely needed.