Van der Woude syndrome, VWS

Overview

Van der Woude syndrome is a condition that affects the development of the face. It is characterised by multiple congenital abnormalities.

Symptoms

The list of signs and symptoms mentioned in various sources for van der Woude syndrome includes the symptoms listed below:

  • Cleft lip
  • Limb abnormalities
  • Cleft palate
  • High arched palate
  • Jaw adhesion
  • Hypodontia
  • Tongue tie
  • Congenital heart defects
  • Depressions (pits) near the center of the lower lip (may appear moist due to the presence of salivary and mucous glands in the pits)
  • Small mounds of tissue on the lower lip
  • Increased risk of delayed language development, learning disabilities, or other mild cognitive problems.

Causes

Mutations in the IRF6 gene (1q32.2-q32.3), involved in epidermal development and in regulation of craniofacial development, are found in over 70% of patients with VWS. The IRF6 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Mutations in the IRF6 gene that cause van der Woude syndrome prevent one copy of the gene in each cell from making any functional protein. A shortage of the IRF6 protein affects the development and maturation of tissues in the face, resulting in the signs and symptoms of van der Woude syndrome. The IRF6 protein is active in cells that give rise to tissues in the head and face. It is also involved in the development of other parts of the body, including the skin and genitals. Whole-gene deletions are a very rare cause of VWS and the frequency of partial-gene deletions is not currently known.

Recently, mutations in the gene GRHL3 (1p36), coding for a Grainyhead-like protein 3 homolog, was found in eight families with VWS with no causative mutations in IRF6.

 

 

Diagnosis

The diagnosis is suspected on the basis of clinical findings and can be confirmed by molecular genetic testing of IRF6. The presence of isolated lip pits, submucous cleft palate, and hypodontia in a parent of a patient with suspected VWS is highly indicative of the diagnosis.

Prognosis

Successful correction of the congenital malformations is the main prognostic factor.

Treatment

In the neonatal period, patients with cleft lip/palate should be monitored for nutritional intake and weight gain. Cleft lip and/or palate should then be managed by a multidisciplinary team with surgical and orthodontic treatment as needed. Speech therapy and audiological evaluation may also be required. Lip pits may be treated surgically for cosmetic purposes and/or to ensure proper lip function.