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.
Van der Woude syndrome (VDWS) is a genetic disorder characterised by the combination of lower lip pits, cleft lip with or without cleft palate (CL/P), and cleft palate only (CPO). The frequency of orofacial clefts ranges from 1:1000 to 1:500 births worldwide, and there are more than 400 syndromes that involve CL/P. VWS is distinct from other clefting syndromes due to the combination of cleft lip and palate (CLP) and CPO within the same family. Other features frequently associated with VWS include hypodontia in 10-81% of cases, narrow arched palate, congenital heart disease, heart murmur and cerebral abnormalities, syndactyly of the hands, polythelia, ankyloglossia, and adhesions between the upper and lower gum pads.
| Van der Woude syndrome | |
|---|---|
| Specialty | Medical genetics  |
The association between lower lip pits and cleft lip and/or palate was first described by Anne Van der Woude in 1954. The worldwide disease incidence ranges from 1:100,000 to 1:40,000.
