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

• Amyoplasia Mandibular Dysostosis
• Mandibulofacial Dysostosis, Guion-Almeida type (MFDGA) 
• Mandibulofacial Dysostosis-Microcephaly Syndrome

What is Mandibulofacial Dysostosis with Microcephaly Syndrome? (Definition/Background Information)

• Mandibulofacial Dysostosis withMicrocephaly(MFDM) Syndrome is a disorder characterized bydevelopmental delayand abnormalities of the head and face
• MFDM Syndrome is caused bymutationsin theEFTUD2geneand isinheritedin anautosomal dominantmanner
• Affected people are usually born with a small head that does not grow at the same rate as the body (progressivemicrocephaly). Developmental delay andintellectual disability can range from mild to severe
• Facial abnormalities may include underdevelopment of the midface and cheekbones; a small lower jaw; small and abnormally-shaped ears; and other distinctive facial features
• Other features of MFDM may includehearing loss,cleft palate, heart problems, abnormalities of the thumbs, abnormalities of the trachea and/or esophagus, andshort stature

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

Who gets Mandibulofacial Dysostosis with Microcephaly Syndrome? (Age and Sex Distribution)

• Mandibulofacial Dysostosis with Microcephaly 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 Mandibulofacial Dysostosis with Microcephaly Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Mandibulofacial Dysostosis with Microcephaly Syndrome is an inherited condition

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 Mandibulofacial Dysostosis with Microcephaly Syndrome? (Etiology)

• Mandibulofacial Dysostosis with Microcephaly Syndrome is caused bymutationsin theEFTUD2gene
• The disorder isinheritedin anautosomal dominantmanner

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

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 Mandibulofacial Dysostosis with Microcephaly Syndrome?

The signs and symptoms of Mandibulofacial Dysostosis with Microcephaly Syndrome may vary in type and severity among affected individuals, and may include the following:

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

• Abnormality of the antihelix
• Absent tragus
• Delayed speech and language development
• Feeding difficulties
• Hypoplasia of the maxilla
• Intellectual disability
• Low-set ears
• Malar flattening
• Micrognathia
• Microtia
• Morphological abnormality of the middle ear
• Postnatal microcephaly
• Preauricular skin tag
• Short nose
• Trigonocephaly
• Underdeveloped tragus
• Upslanted palpebral fissure

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

• Accessory oral frenulum
• Atresia of the external auditory canal
• Epicanthus
• Large earlobe
• Overfolded helix
• Telecanthus

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

• Atrial septal defect
• Ventricular septal defect
• Conductive hearing impairment
• Esophageal atresia
• Proximal placement of thumb
• Seizures

In addition to the above, the following signs and symptoms may be present:

• Anteverted nares
• Choanal atresia
• Deep philtrum
• Downslanted palpebral fissures
• Feeding difficulties in infancy
• Mandibulofacial dysostosis
• Microcephaly
• Midface retrusion
• Progressive microcephaly
• Respiratory distress
• Slender finger

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

How is Mandibulofacial Dysostosis with Microcephaly Syndrome Diagnosed?

Mandibulofacial Dysostosis with Microcephaly 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 tests, to check for the presence of, or to confirm EFTUD2 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 Mandibulofacial Dysostosis with Microcephaly Syndrome?

The complications of Mandibulofacial Dysostosis with Microcephaly Syndrome may include:

• Failure to thrive during neonatal phase
• Low self-esteem due to one’s appearance
• Problems with proper functioning of the heart
• Severe growth delay
• Delay in development of speech
• Intellectual deficiency
• Inability to lead an independent life due to intellectual insufficiency

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

How is Mandibulofacial Dysostosis with Microcephaly Syndrome Treated?

There is no cure for Mandibulofacial Dysostosis with Microcephaly 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 Mandibulofacial Dysostosis with Microcephaly Syndrome be Prevented?

Currently, Mandibulofacial Dysostosis with Microcephaly 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 Mandibulofacial Dysostosis with Microcephaly Syndrome? (Outcomes/Resolutions)

• The prognosis of Mandibulofacial Dysostosis with Microcephaly 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 Mandibulofacial Dysostosis with Microcephaly Syndrome:

Mandibulofacial Dysostosis with Microcephaly Syndrome is also known by the following synonyms:

• Growth Delay-Intellectual Disability-Mandibulofacial Dysostosis-Microcephaly-Cleft Palate Syndrome
• MFDM Syndrome

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

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