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

• Fara-Chlupakova Syndrome
• OFC Syndrome 
• OTFC Syndrome 

What is Otofaciocervical Syndrome? (Definition/Background Information)

• Otofaciocervical Syndrome (OFC Syndrome) is a rare, genetic developmental defect during embryogenesis
• It is characterized by distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit
• Vertebral defects and short stature may also be associated

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

Based on the gene mutation causing the disorder and the mode of inheritance, Otofaciocervical Syndrome is subdivided into:

• Type 1 Otofaciocervical Syndrome: Caused by mutations in EYA1 gene and transmitted in an autosomal dominant manner
• Type 2 Otofaciocervical Syndrome: Caused by mutations in PAX1 gene, with autosomal recessive inheritance

Who gets Otofaciocervical Syndrome? (Age and Sex Distribution)

• Otofaciocervical Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Otofaciocervical Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Otofaciocervical Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for this syndrome

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 Otofaciocervical Syndrome? (Etiology)

The two types of Otofaciocervical Syndrome are caused by mutation(s) in different genes:

• Type 1 Otofaciocervical Syndrome: Caused by mutations in EYA1 gene and transmitted in an autosomal dominant manner
• Type 2 Otofaciocervical Syndrome: Caused by mutations in PAX1 gene, with autosomal recessive inheritance

Autosomal dominant inheritance: 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.

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Otofaciocervical Syndrome?

The signs and symptoms of Otofaciocervical Syndrome may include:

Very frequently present symptoms in 80-99% of the cases:

• Abnormal dermatoglyphics
• Abnormality of the clavicle
• Anteverted nares
• Conductive hearing impairment
• Depressed nasal bridge
• Down-sloping shoulders
• Full cheeks
• Global developmental delay
• High palate
• Hyperreflexia
• Hypertonia
• Macrotia
• Neurological speech impairment
• Preauricular pit
• Protruding ear
• Scapular winging
• Short stature

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the antihelix
• Delayed skeletal maturation

Occasionally present symptoms in 5-29% of the cases:

• Atresia of the external auditory canal
• Facial asymmetry
• Renal hypoplasia/aplasia

(Source: Otofaciocervical Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Otofaciocervical Syndrome Diagnosed?

Otofaciocervical Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative 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 Otofaciocervical Syndrome?

The complications of Otofaciocervical Syndrome may include:

• Intellectual deficiency
• Deafness
• Abnormal kidney function, kidney failure
• Low self-esteem due to physical appearance

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

How is Otofaciocervical Syndrome Treated?

There is no cure for Otofaciocervical Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Otofaciocervical Syndrome be Prevented?

Currently, Otofaciocervical 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 Otofaciocervical Syndrome? (Outcomes/Resolutions)

• The prognosis of Otofaciocervical Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Otofaciocervical Syndrome:

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

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