Klippel-Trenaunay-Weber syndrome

Synonyms: KTW syndrome, Klippel-Trenaunay syndrome, angio-osteohypertrophy syndrome, naevus vasculosus osteohypertrophicus; Parkes-Weber syndrome is a similar entity involving the presence of an arteriovenous malformation with high-flow vessel malformations and characteristic skin capillary changes, with associated skeletal or soft tissue hypertrophy (also known as haemangiectatic hypertrophy).

See also: Sturge-Weber syndrome.

This syndrome is characterised by the presence of the following triad:

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.¹

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.²

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

• The characteristic capillary haemangioma will be visible from birth in the vast majority of cases (98% in one series).²
• 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.
• Varicosities and limb hypertrophy are not always present at birth and may take several years to manifest.
• Abnormal veins and marked varicosities may be present.
• 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.
• If the head is affected then the syndrome may cause macrocephaly and/or mental retardation.
• Lymphoedema may complicate the condition and contribute to the limb enlargement.
• Rarely, the affected limb may show atrophy rather than hypertrophy.
• Thrombophlebitis is a common consequence in patients with large venous varicosities.
• 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.
• Other features include:¹
  • Spina bifida
  • Hypospadias
  • Hyperhidrosis
  • Hypertrichosis
  • Paraesthesiae
  • Decalcification of affected bones
  • Chronic venous insufficiency
  • Stasis dermatitis
  • Poor wound healing
  • Venous ulceration

• 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 may be carried out, 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.³

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

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.
• Women who have the syndrome should avoid the use of hormonal contraceptive methods, due to the increased risk of venous thrombosis.
• Pregnant women with KTW syndrome need careful monitoring due to a range of haematological, obstetric and anaesthetic complications.⁴

Active/surgical measures

• Limb-length discrepancy may be treated with orthoses or orthopaedic surgery, depending on its severity.
• Laser therapy can be used to lessen the cosmetic effect of the cutaneous stain.
• Surgery may be used to treat severe venous malformations but remains controversial as long-term outcomes appear to be altered little by such intervention.
• Endovenous laser therapy of the greater saphenous vein appears to help some cases of lower limb varicosity.
• 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 function⁵
• 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.³ 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.