What are the other Names for this Condition? (Also known as/Synonyms)

• Cleft Lip and/or Palate with Mucous Cysts of Lower Lip
• Lip-Pit Syndrome
• VDWS (Van Der Woude Syndrome)

What is Van Der Woude Syndrome? (Definition/Background Information)

• Cleft Lip and Palate with Mucous Cysts of Lower Lip, also known as Van Der Woude Syndrome (VWS), is a rare congenital genetic dysmorphic syndrome characterized by paramedian lower-lip fistulae, cleft lip with or without cleft palate, or isolated cleft palate
• 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. Rarely, mutations in the gene GRHL3 (1p36), coding for a Grainyhead-like protein 3 homolog may cause Cleft Lip and/or Palate with Mucous Cysts of Lower Lip, and is reported in 8 families
• The diagnosis is suspected on the basis of clinical findings and can be confirmed by molecular genetic testing of IRF6
• 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
• Successful correction of the congenital malformations is the main prognostic factor

(Source: Van der Woude Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Van Der Woude Syndrome? (Age and Sex Distribution)

• Van Der Woude Syndrome represents the most common single-gene cause of cleft lip/cleft palate, i.e. 2% of all individuals with cleft lip/palate
• Estimated incidence at birth is between 1/35,000 and 1/100,000 in European and Asian populations 
• Males and females are affected equally

(Source: Van der Woude Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

What are the Risk Factors for Van Der Woude Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Van Der Woude Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Van Der Woude Syndrome? (Etiology)

• In over 70% of Van Der Woude Syndrome cases, mutations in the IRF6 gene (1q32.2-q32.3), involved in epidermal development and in regulation of craniofacial development, is the cause of the condition 
• Rarely, mutations in the gene GRHL3 (1p36), coding for a Grainyhead-like protein 3 homolog may cause Cleft Lip and/or Palate with Mucous Cysts of Lower Lip, and is reported in 8 families

(Source: Van der Woude Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

• When Cleft Lip and/or Palate with Mucous Cysts of Lower Lip runs in families, it is inherited as an autosomal dominant trait

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring

What are the Signs and Symptoms of Van Der Woude Syndrome?

The common signs and symptoms of Van Der Woude Syndrome may include:

• Paramedian lower-lip pits (fistulae, usually bilateral), observed in over 80% of affected individuals 
• Small mounds with a sinus tract leading from a mucous gland of the lip
• Cleft lip; cleft palate 
• A combination of cleft lip and cleft palate
• Hypodontia (missing teeth)
• Dental hypoplasia 

The non-classic signs of VWS may include 

• Single unilateral lip pits 
• Submucous cleft
• Bifid uvula 
• Ankyloglossia
• Limb abnormalities such as skin folds and syndactyly
• Sensorineural hearing loss

(Source: Van der Woude Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Van Der Woude Syndrome Diagnosed?

Van Der Woude Syndrome (Cleft Lip and/or Palate with Mucous Cysts of Lower Lip) is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Checking for the presence of isolated lip pits, cleft palate, and hypodontia in a parent of a an affected individual with suspected Van Der Woude Syndrome
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Prenatal diagnosis of the condition in late pregnancy through ultrasound imaging of fetus
• Molecular genetic testing for IRF6 gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Van Der Woude Syndrome?

The complications of Van Der Woude Syndrome may include:

• Dribbling and infection due to lip pits 
• Decreased food intake due to non-development of teeth
• Inadequate weight gain
• Speech impediment
• Hearing problems
• Low self-esteem owing to appearance

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Van Der Woude Syndrome Treated?

The treatment for Van Der Woude Syndrome may include the following:

• Monitoring newborns for nutritional intake and weight gain 
• Surgical repair of cleft lip or palate or both
• Surgical treatment of lip pits to correct lip function, or improve appearance
• Orthodontic treatment as needed 
• Speech therapy

(Source: Van der Woude Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How can Van Der Woude Syndrome be Prevented?

Currently, Van Der Woude Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Van Der Woude Syndrome? (Outcomes/Resolutions)

• The long-term outlook (prognosis) for people with Van Der Woude Syndrome varies and largely depends on the signs and symptoms present in each person
• Successful correction of the congenital malformations is the main prognostic factor

(Source: Van der Woude Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Van Der Woude Syndrome:

Van Der Woude Syndrome is also known by the following names:

• Cleft Lip and Palate with Mucous Cysts of Lower Lip
• Cleft Lip or Palate with Mucous Cysts of Lower Lip

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/