Genetics and Epidemiology
- Van der Woude syndrome is inherited as an autosomal dominant disease caused by a mutation in a single gene.
- The disease has high penetrance at about 96%.
- Phenotypic expression varies from lower lip pits with cleft lip and cleft palate to no visible abnormalities.
- Approximately 88% of VWS patients display lower lip pits.
- VWS is the most common orofacial clefting syndrome, accounting for 2% of CLP cases.
- Prevalence of VWS is 1 in 35,000 to 1 in 100,000 births.
- Equal occurrence in males and females.
- Higher prevalence in certain populations (e.g., Native Americans, Finnish).

Pathophysiology
- Lip pits occur during embryogenesis due to IRF6 mutations.
- Cleft lip and cleft palate develop during embryonic development.
- There are three types of lip pits: midline upper, comissural, and lower lip.
- Lip pits extend into the orbicularis oris muscle, ending in blind sacs surrounded by mucous glands.
- Mucous is sometimes excreted when the muscles contract.

Diagnosis and Differential Diagnosis
- Clinical diagnosis is based on orofacial clefts and lip pits.
- Submucous cleft palate may not be detected except through finger palpation.
- Approximately 15% of VWS cases with orofacial clefts, without prominent lip pits, cannot be easily distinguished from non-syndromic forms of orofacial clefting.
- Dentists may detect hypodontia commonly associated with VWS.
- VWS clinical signs are similar to those of popliteal pterygium syndrome (PPS).
- Differential diagnosis includes popliteal pterygium syndrome, orofacial digital syndrome, Stickler syndrome, Pierre Robin sequence, and Robinow syndrome.

Genetic Counseling and Treatment
- Genetic counseling involves discussing disease transmission in an autosomal dominant manner.
- Parents have a 50% chance of passing on their mutated IRF6 allele to their child.
- Cleft patients with lip pits have a ten times greater risk of having a child with cleft lip with or without cleft palate.
- Different types of clefts may occur horizontally and vertically within the same pedigree.
- A complete family history is important to ensure the patient does not have non-syndromic clefting.
- Autosomal dominant inheritance pattern.
- Genetic testing (e.g., mutation screening of IRF6 gene).
- Prenatal diagnosis options (e.g., ultrasound, DNA analysis).
- Multidisciplinary approach to treatment (e.g., surgery, orthodontics, speech therapy).
- Psychological support for affected individuals and families.

Cardinal Signs, Associated Features, and Treatment
- Cardinal signs of Van der Woude syndrome include cleft lip and/or cleft palate, lip pits, hypodontia, fistulas, and abnormal frenulum.
- Associated features may include hearing loss, syndactyly, hypoplasia of the nasal alae, ankyloglossia, and delayed speech development.
- Lip pits may be surgically removed for aesthetic reasons or discomfort due to inflammation or chronic saliva excretion.
- Spontaneous shrinkage of lip pits has occurred in rare cases.
- Chronic inflammation can cause squamous-cell carcinoma.
- Complete removal of the lip pit canal is essential to prevent mucoid cysts.
- Other associated conditions are treated as they would be if they were non-syndromic.