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

• Mohr-Majewski Syndrome
• OFD Syndrome, Baraitser-Burn type
• Oral-Facial-Digital Syndrome Type IV

What is Orofaciodigital Syndrome 4? (Definition/Background Information)

• Orofaciodigital Syndrome 4 (OFDS 4) is one of a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes)
• Specific features, while variable, commonly include non-cancerous tumors (hamartomas) of the tongue, polydactyly of the hands and feet, severe clubfoot, and shortening and bowing of the middle portion of the lower leg (mesomelic limb shortening with tibial dysplasia)
• Orofaciodigital Syndrome 4 is inherited in an autosomal recessive manner. The condition appears to be caused by mutations in the tectonic family member 3 gene (TCTN3)

(Source: Orofaciodigital Syndrome 4; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Orofaciodigital Syndrome 4? (Age and Sex Distribution)

• Orofaciodigital Syndrome 4 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 Orofaciodigital Syndrome 4? (Predisposing Factors)

• A positive family history may be an important risk factor, since Orofaciodigital Syndrome 4 is an inherited condition
• Currently, no other risk factors have been clearly identified for OFDS 4

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 Orofaciodigital Syndrome 4? (Etiology)

• Orofaciodigital Syndrome 4 is inherited in an autosomal recessive manner
• The condition appears to be caused by mutations in the tectonic family member 3 gene (TCTN3)

(Source: Orofaciodigital Syndrome 4; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal recessive: 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 Orofaciodigital Syndrome 4?

The signs and symptoms of Orofaciodigital Syndrome 4 may include:

• Accessory oral frenulum
• Brachydactyly
• Cerebral atrophy
• Clinodactyly
• Epicanthus
• Foot polydactyly
• Hamartoma of tongue
• Hand polydactyly
• High palate
• Lobulated tongue
• Pectus excavatum
• Porencephalic cyst
• Short finger
• Short tibia
• Toe syndactyly
• Tongue nodules

Based on the frequency of symptoms observed, the following information may be noted:

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

• Abnormality of oral frenula
• Abnormality of the gingiva
• Abnormality of the tongue
• Absent testis
• Aplasia/hypoplasia of the tibia
• Choanal atresia
• Conductive hearing impairment
• Decreased testicular size
• Depressed nasal ridge
• Finger syndactyly
• Genu varum
• Hamartoma
• Hypertelorism
• Intellectual disability
• Intrauterine growth retardation
• Joint dislocation
• Laryngomalacia
• Low-set ears
• Median cleft lip
• Microcephaly
• Micrognathia
• Micromelia
• Microtia, third degree
• Monorchism
• Oligohydramnios
• Oral synechia
• Postaxial hand polydactyly
• Posteriorly rotated ears
• Recurrent respiratory infections
• Retrognathia
• Severe short stature
• Short nose
• Specific learning disability
• Wide nose

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

• Bifid uvula 
• Camptodactyly of finger 
• Cerebral cortical hemiatrophy 
• Failure to thrive 
• Feeding difficulties 
• High, narrow palate
• Proptosis 
• Split hand 
• Subcortical cerebral atrophy 
• Submucous cleft hard palate

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

• Abnormality of cardiovascular system morphology
• Absent crus of helix
• Anal atresia
• Bilateral lung agenesis 
• Hypoplastic toenails 
• Perineal fistula
• Primary adrenal insufficiency
• Pulmonary hypoplasia   
• Rectal atresia 
• Rectovaginal fistula
• Renal agenesis                    
• Short philtrum

(Source: Orofaciodigital Syndrome 4; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Orofaciodigital Syndrome 4 Diagnosed?

Orofaciodigital Syndrome 4 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

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 Orofaciodigital Syndrome 4?

The complications of Orofaciodigital Syndrome 4 may include:

• Brain abnormalities
• Failure to thrive 
• Walking difficulties
• Multiple abnormalities involving various organs

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

How is Orofaciodigital Syndrome 4 Treated?

There is no cure for Orofaciodigital Syndrome 4, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Orofaciodigital Syndrome 4 be Prevented?

Currently, Orofaciodigital Syndrome 4 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 Orofaciodigital Syndrome 4? (Outcomes/Resolutions) 

• The prognosis of Orofaciodigital Syndrome 4 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 Orofaciodigital Syndrome 4:

Orofaciodigital Syndrome 4 is also known by the following names:

• Baraitser-Burn Syndrome
• OFD Syndrome 4
• OFD Syndrome with Tibial Defects
• Oral Facial Digital Syndrome 4 (OFD4)
• Oral Facial Digital Syndrome Type 4 (OFDS 4)
• Orofaciodigital Syndrome IV
• Orofaciodigital Syndrome with Tibial Dysplasia

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

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