Van der Woude Syndrome: Introduction

Van der Woude syndrome (VWS) is a rare genetic disorder characterized by orofacial clefting and distinctive lower lip pits. It is the most common syndromic form of cleft lip and palate, accounting for approximately 2% of all cases. VWS is an autosomal dominant condition with high penetrance and variable expressivity.

Key points:

• Prevalence: Estimated at 1 in 35,000 to 1 in 100,000 live births
• Genetic cause: Mutations in the IRF6 gene (1q32-q41) in about 70% of cases
• Inheritance: Autosomal dominant with 95-99% penetrance
• Variable expressivity: Phenotype can range from isolated lip pits to complete cleft lip and palate

Clinical Features of Van der Woude Syndrome

Primary Features:

• Lower lip pits (80-85% of cases)
  • Usually bilateral and symmetrical
  • Located on the vermilion border of the lower lip
  • Can be deep sinuses or slight depressions
  • May secrete saliva due to connection with minor salivary glands
• Orofacial clefting (50-70% of cases)
  • Cleft lip with or without cleft palate
  • Isolated cleft palate
  • Submucous cleft palate

Associated Features:

• Hypodontia (missing teeth, especially second premolars)
• Syngnathia (adhesion of the jaws)
• Ankyloglossia (tongue-tie)
• Narrow, high-arched palate
• Limb anomalies (rare)
  • Syndactyly
  • Polydactyly
  • Club foot
• Normal intelligence and development (in most cases)

Popliteal Pterygium Syndrome:

A more severe allelic disorder with additional features:

• Popliteal pterygium (webbing behind the knees)
• Genital anomalies
• Syngnathia
• Toe/nail abnormalities

Diagnosis of Van der Woude Syndrome

Clinical Diagnosis:

Based on the presence of characteristic features:

• Lower lip pits with or without cleft lip/palate
• Cleft lip/palate with a family history of lip pits

Genetic Testing:

• Molecular genetic testing of IRF6 gene
  • Sequence analysis
  • Deletion/duplication analysis
• Consider testing for other genes (GRHL3) if IRF6 testing is negative

Differential Diagnosis:

• Isolated cleft lip/palate
• Popliteal pterygium syndrome
• Kabuki syndrome
• Branchio-oculo-facial syndrome
• Orofacial digital syndrome type 1

Additional Evaluations:

• Comprehensive oral and maxillofacial examination
• Speech and language assessment
• Dental evaluation
• Audiological assessment
• Genetic counseling

Management of Van der Woude Syndrome

Management of Van der Woude syndrome requires a multidisciplinary approach:

Surgical Interventions:

• Cleft lip repair (typically at 3-6 months of age)
• Cleft palate repair (typically at 9-18 months of age)
• Lip pit excision (if desired, often delayed until adolescence)
  • Consider risks: scarring, sensory changes, asymmetry
• Alveolar bone grafting (for cleft alveolus, typically at 6-9 years)
• Orthognathic surgery (if needed in adolescence)

Dental and Orthodontic Care:

• Regular dental check-ups and hygiene
• Orthodontic treatment for malocclusion
• Management of hypodontia (may include implants or prostheses)

Speech and Language Therapy:

• Early intervention for speech and language development
• Management of velopharyngeal insufficiency
• Ongoing assessment and therapy as needed

Audiological Management:

• Regular hearing assessments
• Management of conductive hearing loss (common in cleft palate)

Psychological Support:

• Counseling for patients and families
• Support for self-esteem and social integration

Genetic Counseling:

• Discussion of inheritance pattern and recurrence risk
• Prenatal diagnosis options for future pregnancies

Long-term Follow-up:

• Regular evaluations by cleft/craniofacial team
• Monitoring for associated features and complications
• Transition of care from pediatric to adult services