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Disease Profile

Mandibulofacial dysostosis with microcephaly

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other names (AKA)

Mandibulofacial dysostosis, Guion-Almeida type; MFDGA; MFDM;


Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases;


Mandibulofacial dysostosis with microcephaly (MFDM) is a disorder characterized by developmental delay and abnormalities of the head and face. Affected people are usually born with a small head that does not grow at the same rate as the body (progressive microcephaly). Developmental delay and intellectual 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 include hearing loss, cleft palate, heart problems, abnormalities of the thumbs, abnormalities of the trachea and/or esophagus, and short stature. MFDM is caused by mutations in the EFTUD2 gene and is inherited in an autosomal dominant manner.[1][2]


Mandibulofacial dysostosis with microcephaly (MFDM) may affect multiple parts of the body but primarily affects the head and face. People with MFDM are usually born with a small head (microcephaly) which does not grow at the same rate as the body. Intellectual disability ranges from mild to severe and is present in almost all affected people. Speech and language problems are also common.[1][2]

Facial abnormalities in affected people may include underdevelopment (hypoplasia) of the midface and cheekbones; a small lower jaw (micrognathia); small and malformed ears; facial asymmetry; and cleft palate. Other head and facial features may include a metopic ridge; upor downslanting palpebral fissures; a prominent glabella (space between the eyebrows); a broad nasal bridge; a bulbous nasal tip; and an everted lower lip. Abnormalities of the ear canal, ear bones, or inner ear often lead to hearing loss. Affected people can also have a blockage of the nasal passages (choanal atresia) that can cause respiratory problems.[1][2]

Other signs and symptoms in some people with MFDM may include esophageal atresia, congenital heart defects, thumb anomalies, and/or short stature.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Abnormality of the antihelix
Absent tragus
Cleft palate
Cleft roof of mouth
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

Feeding difficulties
Feeding problems
Poor feeding

[ more ]

Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Low-set ears
Low set ears
Lowset ears

[ more ]

Malar flattening
Zygomatic flattening
Little lower jaw
Small jaw
Small lower jaw

[ more ]

Small ears
Underdeveloped ears

[ more ]

Morphological abnormality of the middle ear
Middle ear malformation
Postnatal microcephaly
Preauricular skin tag
Short nose
Decreased length of nose
Shortened nose

[ more ]

Short stature
Decreased body height
Small stature

[ more ]

Triangular skull shape
Wedge shaped skull

[ more ]

Underdeveloped tragus
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
30%-79% of people have these symptoms
Accessory oral frenulum
Atresia of the external auditory canal
Absent ear canal
Eye folds
Prominent eye folds

[ more ]

Large earlobe
Fleshy earlobe
Fleshy earlobes
Prominent ear lobes
prominent ear lobules

[ more ]

Overfolded helix
Overfolded ears
Preaxial hand polydactyly
Extra thumb
Corners of eye widely separated
5%-29% of people have these symptoms
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

Esophageal atresia
Birth defect in which part of esophagus did not develop
Proximal placement of thumb
Attachment of thumb close to wrist
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
Percent of people who have these symptoms is not available through HPO
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

Autosomal dominant inheritance
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity

[ more ]

Deep philtrum
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
Feeding difficulties in infancy
Global developmental delay
Mandibulofacial dysostosis
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

Slender finger
Narrow fingers
Slender fingers
thin fingers

[ more ]



Mandibulofacial dysostosis with microcephaly (MFDM) is caused by mutations in the EFTUD2 gene. This gene gives the body instructions for making part of spliceosomes, which help process a type of RNAa chemical cousin of DNA that serves as a genetic blueprint for making proteins. Mutations in EFTUD2 impair the production or function of the enzyme from the gene, which impairs the processing of mRNA. However, at this time, it is not clear how this process causes the specific symptoms of MFDM.[1]


Yes. Genetic testing is available for mandibulofacial dysostosis with microcephaly (MFDM) and confirms the diagnosis in virtually all people suspected of having MFDM. There are two approaches to genetic testing for this condition. One is sequence analysis of the EFTUD2 gene to identify a mutation (which detects ~91% of affected people), and the other is deletion analysis (which detects ~9%), for people in whom sequencing does not detect a mutation.[2]

When a diagnosis of MFDM is strongly suspected but genetic testing is inconclusive, a clinical diagnosis may still be appropriate. However, given the high sensitivity of genetic testing for this condition, other disorders with overlapping features should first be carefully considered.[2]

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.


Individualized treatment of craniofacial features is managed by a multidisciplinary team which may include various specialists. Surgery may be needed for a variety of abnormalities, in the newborn period or beyond. Treatment of hearing loss is individualized, and may involve conventional hearing aids, bone-anchored hearing aid, and/or cochlear implants. Occupational, physical, and/or speech/language therapies are involved as needed to optimize developmental outcome.[2]

Additional treatment information is available on GeneReviews' Web site.


Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Mandibulofacial dysostosis with microcephaly. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Mandibulofacial dysostosis with microcephaly. Click on the link to view a sample search on this topic.


            1. Mandibulofacial dysostosis with microcephaly. Genetics Home Reference. September, 2014; https://ghr.nlm.nih.gov/condition/mandibulofacial-dysostosis-with-microcephaly.
            2. Matthew Lines, Taila Hartley, and Kym Boycott. Mandibulofacial Dysostosis with Microcephaly. GeneReviews. July 3, 2014; https://www.ncbi.nlm.nih.gov/books/NBK214367/.

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