Van der Woude syndrome is a genetic condition that impacts the development of the face during pregnancy. It is a rare condition, with an estimated incidence between 1 in 35,000 and 1 in 100,000 people. This condition is the most frequently observed single-gene cause of cleft lip and palate.
Core Physical Characteristics
The most prominent features of Van der Woude syndrome are in the oral and facial regions. Many individuals are born with depressions near the center of the lower lip, known as lip pits or paramedian sinuses. These pits may appear as small mounds of tissue or indentations and can sometimes look moist due to the presence of salivary glands that connect to them.
In addition to lip pits, many individuals are born with a cleft lip, a cleft palate, or both. A cleft lip is an opening in the upper lip, while a cleft palate is an opening in the roof of the mouth. The presentation of these characteristics varies widely; some individuals may have only lip pits, while others might have a severe cleft with no visible lip pits. Approximately 88% of people with the syndrome have lower lip pits.
The severity and combination of symptoms can differ greatly. This variability means that some family members may have very noticeable features, while others have such mild signs that they are unaware of the condition. Another less common feature is the congenital absence of some teeth, a condition known as hypodontia.
Genetic Origins
Van der Woude syndrome arises from a mutation in a specific gene, most commonly the IRF6 gene. This gene provides instructions for a protein active in cells that form tissues in the head and face during early development. A mutation in the IRF6 gene disrupts the normal maturation of these facial tissues, leading to the syndrome’s features. In about five percent of cases, mutations in another gene, GRHL3, have been identified as the cause.
The condition is inherited in an autosomal dominant pattern. This means only one copy of the altered gene, inherited from one parent, is sufficient to cause the disorder. A parent with the gene mutation has a 50% chance of passing the condition on to each of their children.
While often passed down through families, the syndrome can also occur in individuals with no family history of the condition. This happens through a spontaneous or “de novo” mutation. Because of the high penetrance of the gene, a person carrying the mutation will likely show some signs of the syndrome, though the severity can be unpredictable.
Diagnosis and Management
The diagnosis of Van der Woude syndrome is made based on a clinical examination that identifies the characteristic physical features. The presence of lower lip pits, especially in combination with a cleft lip or palate, is a strong indicator. Observing these signs in a parent of a child with a suspected case further supports the diagnosis. Genetic testing can be performed to identify a mutation in the IRF6 gene, which is found in over 70% of affected individuals.
Management of the syndrome’s features is handled by a multidisciplinary team of specialists. Surgical intervention is a common part of management. Plastic surgeons repair the cleft lip, typically around three months of age, and the cleft palate at approximately 10 months. Lip pits can also be surgically removed for cosmetic reasons or to improve lip function.
Beyond surgery, other specialists play ongoing roles. Orthodontists address dental issues like missing teeth or a narrow, high-arched palate. Speech-language pathologists work with individuals who may have difficulties with speech development as a result of a cleft palate. This coordinated care ensures its physical manifestations can be effectively managed to improve both function and appearance.