Van der Woude Syndrome

Overview

Van der Woude syndrome (VWS) is a rare congenital disorder primarily characterized by cleft lip and/or cleft palate along with distinctive pits or mounds on the lower lip. It is one of the most common syndromic forms of clefting and accounts for up to 2% of all cases of cleft lip and palate. The condition is autosomal dominant and may present with a wide range of severity, from subtle lip pits to more severe orofacial clefts. Despite its facial manifestations, individuals with VWS typically have normal intelligence and development.

Causes

Van der Woude syndrome is caused by mutations in the IRF6 gene (interferon regulatory factor 6), which plays a crucial role in the development of tissues in the face and oral cavity. The condition is inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. However, the expression of the syndrome can vary greatly, even within the same family. In rare cases, mutations in other genes such as GRHL3 may also be implicated.

Symptoms

The symptoms of Van der Woude syndrome can vary from person to person, but the most common features include:

• Lower lip pits: Small depressions or mounds usually located on either side of the midline of the lower lip. These may excrete saliva.

• Cleft lip and/or cleft palate: Can range from mild to severe and may affect one or both sides of the mouth.

• Hypodontia: Congenital absence of teeth, particularly the incisors or premolars.

• Additional anomalies: Less commonly, individuals may have limb anomalies, syngnathia (fusion of the jaws), or bifid uvula.

Diagnosis

Diagnosis of Van der Woude syndrome is typically made based on clinical findings. The presence of lip pits in a child with a cleft lip or palate is a key indicator. Diagnostic steps include:

• Physical examination: Identification of characteristic facial features, especially lip pits and clefts.

• Family history: A review of relatives may reveal a pattern of clefting or lip pits consistent with autosomal dominant inheritance.

• Genetic testing: Molecular analysis to detect mutations in the IRF6 gene confirms the diagnosis and can be useful for family planning.

Treatment

Treatment of Van der Woude syndrome is tailored to the individual's specific symptoms and often involves a multidisciplinary team. Typical interventions include:

• Surgical repair of clefts: Typically performed in infancy or early childhood to close the cleft lip or palate.

• Excision of lip pits: May be done for cosmetic reasons or if they cause recurrent infections or saliva leakage.

• Dental care: Management of hypodontia may require orthodontic treatment, dental prosthetics, or implants.

• Speech therapy: Especially for individuals with cleft palate to address speech and resonance issues.

Prognosis

The prognosis for individuals with Van der Woude syndrome is generally excellent. With appropriate surgical and therapeutic interventions, most affected individuals can achieve normal function and appearance. Intellectual development is typically unaffected. Genetic counseling is recommended for affected families due to the hereditary nature of the disorder and the variable expression seen among carriers.