Klippel-Trenaunay-Weber Syndrome (KTWS)

Klippel-Trenaunay-Weber syndrome is a rare congenital malformation characterized by the triad of capillary malformations (port-wine stains), soft tissue and bone hypertrophy, and venous/lymphatic malformations.

Key Points

• Prevalence: Approximately 1:100,000 live births
• First described in 1900 by French physicians Klippel and Trenaunay
• No gender or racial predilection
• Usually affects a single limb (85% cases)
• Lower extremities most commonly affected (95%)

Classic Triad

• Capillary Malformations (Port-Wine Stains):
  • Present at birth in 98% of cases
  • Usually unilateral distribution
  • Color varies from pink to dark purple
  • May darken and thicken with age
  • Often follows dermatomal patterns
  • Can involve any body part but commonly affects limbs
• Venous and Lymphatic Malformations:
  • Superficial and deep abnormal veins
  • Persistent embryonic veins
  • Venous anomalies types:
    • Marginal vein of Servelle
    • Lateral embryonic vein
    • Persistent sciatic vein
    • Klippel-Trenaunay vein
  • Lymphatic manifestations:
    • Lymphedema
    • Lymphatic vesicles
    • Macrocystic lymphatic malformations
• Soft Tissue and Bone Hypertrophy:
  • Usually apparent at birth or early childhood
  • Progressive growth during childhood
  • May cause leg length discrepancy
  • Can affect:
    • Skeletal system
    • Muscles
    • Subcutaneous tissues
    • Internal organs in affected areas

Associated Features

• Musculoskeletal:
  • Scoliosis
  • Gait abnormalities
  • Joint contractures
  • Arthritis
  • Hammer toes
• Visceral Involvement:
  • Gastrointestinal tract bleeding
  • Hematuria
  • Rectal bleeding
  • Hemorrhoids

Diagnostic Criteria

• Clinical Diagnosis:
  • Presence of at least 2 of 3 cardinal features
  • Usually diagnosed in infancy or early childhood
• Imaging Studies:
  • MRI/MRV:
    • Extent of soft tissue involvement
    • Venous malformation mapping
    • Muscle involvement
  • Ultrasound:
    • Superficial vascular malformations
    • Deep venous system assessment
    • Blood flow characteristics
  • Lymphoscintigraphy:
    • Lymphatic system evaluation
    • Lymphedema assessment
  • Arteriography:
    • Rarely needed
    • Used when arterial involvement suspected

Genetic Basis

• Molecular Genetics:
  • PIK3CA gene mutations identified in affected tissues
  • Part of the PIK3CA-related overgrowth spectrum (PROS)
  • Somatic mutations - post-zygotic
  • Mosaic pattern of mutation distribution
• Inheritance Pattern:
  • Typically sporadic occurrence
  • No increased familial risk
  • Rare familial cases reported

Treatment Approaches

• Conservative Management:
  • Compression therapy
    • Graduated compression garments
    • Pneumatic compression devices
    • Regular monitoring for skin breakdown
  • Physical therapy
    • Range of motion exercises
    • Gait training
    • Muscle strengthening
  • Pain management
  • Psychological support
• Interventional Procedures:
  • Sclerotherapy:
    • For venous malformations
    • Multiple sessions often required
    • Careful patient selection essential
  • Laser Therapy:
    • For port-wine stains
    • Pulsed dye laser most common
    • Early treatment recommended
  • Surgical Interventions:
    • Debulking procedures
    • Epiphysiodesis for leg length discrepancy
    • Vein stripping
    • Amputation (rare, severe cases)
• Novel Therapies:
  • PIK3CA inhibitors (investigational)
  • Targeted molecular therapy
  • Antiangiogenic agents

Potential Complications

• Vascular Complications:
  • Deep vein thrombosis
  • Pulmonary embolism
  • Chronic venous insufficiency
  • Hemorrhage
• Orthopedic Issues:
  • Progressive limb length discrepancy
  • Angular deformities
  • Pathological fractures
  • Degenerative joint disease
• Psychological Impact:
  • Body image concerns
  • Social adjustment issues
  • Depression and anxiety
• Quality of Life Issues:
  • Chronic pain
  • Limited mobility
  • Recurrent infections
  • School/work adaptations needed

Related Conditions

• Parkes Weber Syndrome:
  • Includes arteriovenous malformations
  • High-flow vascular malformations
  • More aggressive clinical course
• PROS Spectrum Disorders:
  • CLOVES syndrome
  • Megalencephaly-capillary malformation syndrome
  • Isolated lymphatic malformation
• Other Vascular Anomalies:
  • Sturge-Weber syndrome
  • Proteus syndrome
  • Maffucci syndrome