Mandibulofacial dysostosis with microcephaly

Title

Other Names:

Mandibulofacial dysostosis, Guion-Almeida type; MFDGA; MFDM; Mandibulofacial dysostosis, Guion-Almeida type; MFDGA; MFDM; Mandibulofacial dysostosis-microcephaly syndrome; Growth delay - intellectual disability - mandibulofacial dysostosis - microcephaly - cleft palate; MFDM syndrome; Growth delay-intellectual disability-mandibulofacial dysostosis-microcephaly-cleft palate syndrome See More

Categories:

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases; Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases; Musculoskeletal Diseases; Nervous System Diseases See More

Summary Summary

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]

Last updated: 7/27/2015

Symptoms Symptoms

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; up- or 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]

Last updated: 7/27/2015

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.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormality of the antihelix		0009738
Absent tragus		0011268
Cleft palate	Cleft roof of mouth	0000175
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 ]	0000750
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
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 ]	0000327
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Malar flattening	Zygomatic flattening	0000272
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Microtia	Small ears Underdeveloped ears [ more ]	0008551
Morphological abnormality of the middle ear	Middle ear malformation	0008609
Postnatal microcephaly		0005484
Preauricular skin tag		0000384
Short nose	Decreased length of nose Shortened nose [ more ]	0003196
Short stature	Decreased body height Small stature [ more ]	0004322
Trigonocephaly	Triangular skull shape Wedge shaped skull [ more ]	0000243
Underdeveloped tragus		0011272
Upslanted palpebral fissure	Upward slanting of the opening between the eyelids	0000582
30%-79% of people have these symptoms
Accessory oral frenulum		0000191
Atresia of the external auditory canal	Absent ear canal	0000413
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Large earlobe	Fleshy earlobe Fleshy earlobes Prominent ear lobes prominent ear lobules [ more ]	0009748
Overfolded helix	Overfolded ears	0000396
Preaxial hand polydactyly	Extra thumb	0001177
Telecanthus	Corners of eye widely separated	0000506
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 ]	0001631
Conductive hearing impairment	Conductive deafness Conductive hearing loss [ more ]	0000405
Esophageal atresia	Birth defect in which part of esophagus did not develop	0002032
Proximal placement of thumb	Attachment of thumb close to wrist	0009623
Seizure		0001250
Ventricular septal defect	Hole in heart wall separating two lower heart chambers	0001629
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 ]	0000463
Autosomal dominant inheritance		0000006
Autosomal recessive inheritance		0000007
Choanal atresia	Blockage of the rear opening of the nasal cavity Obstruction of the rear opening of the nasal cavity [ more ]	0000453
Deep philtrum		0002002
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Feeding difficulties in infancy		0008872
Global developmental delay		0001263
Mandibulofacial dysostosis		0005321
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Midface retrusion	Decreased size of midface Midface deficiency Underdevelopment of midface [ more ]	0011800
Progressive microcephaly	Progressively abnormally small cranium Progressively abnormally small skull [ more ]	0000253
Respiratory distress	Breathing difficulties Difficulty breathing [ more ]	0002098
Slender finger	Narrow fingers Slender fingers thin fingers [ more ]	0001238

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Last updated: 7/1/2020

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Cause Cause

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 RNA- a 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]

Last updated: 7/30/2015

Inheritance Inheritance

Mandibulofacial dysostosis with microcephaly (MFDM) is inherited in an autosomal dominant manner. This means that having one mutated copy of the responsible gene in each cell of the body is enough to cause signs and symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated copy of the gene.

Most cases of MFDM are due to new mutations that occur for the first time in the affected person (called de novo mutations), and are not inherited from a parent. In other cases, an affected person inherits the mutation from a parent. The parent may be mildly affected or may be unaffected. Sometimes, an unaffected parent has the mutation only in some or all of their sperm or egg cells (not their body cells), which is known as germline mosaicism.^[1]

Last updated: 7/30/2015

Diagnosis Diagnosis

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.

Last updated: 7/27/2015

Treatment Treatment

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.

Last updated: 7/30/2015

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis includes Treacher-Collins, Nager and CHARGE syndromes, as well as postaxial acrofacial dysostosis. Visit the Orphanet disease page for more information.

Organizations Organizations

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

Ameriface
PO Box 751112
Las Vegas, NV 89136
Toll-free: 888-486-1209
Telephone: 702-769-9264
E-mail: info@ameriface.org
Website: http://www.ameriface.org
Children's Craniofacial Association
13140 Coit Road Suite 517
Dallas, TX 75240
Toll-free: 1-800-535-3643
Telephone: +1-214-570-9099
Fax: +1-214-570-8811
E-mail: contactCCA@ccakids.com
Website: https://ccakids.org/
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: faces@faces-cranio.org
Website: http://www.faces-cranio.org/
The Arc of the United States
1825 K Street, NW
Suite 1200
Washington, DC, DC 20006
Toll-free: 1-(800) 433-5255
Telephone: +1-202-534-3700
Fax: +1-202-534-3731
E-mail: info@thearc.org
Website: https://www.thearc.org/
World Craniofacial Foundation
P.O. Box 515838
Dallas, TX 75251-5838
Toll-free: 800-533-3315
Telephone: 972-566-6669
Fax: 972-566-3850
E-mail: info@worldcf.org
Website: http://www.worldcf.org/

Social Networking Websites

Visit the Mandibulofacial Dysostosis with Microcephaly group on Facebook.

Organizations Providing General Support

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Learn More 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.

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GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My son was recently diagnosed with mandibulofacial dysostosis Guion-Almeida type. How accurate is the genetic testing in diagnosing this disease? Is mandibulofacial dysostosis Guion-Almeida type considered a rare genetic condition? Are there any other names for this condition? Could you please direct me to information about this condition? See answer

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References References

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

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