The following information may help to address your question:
What is mandibulofacial dysostosis with microcephaly?
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
Is genetic testing available for mandibulofacial dysostosis with microcephaly?
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
Is mandibulofacial dysostosis with microcephaly considered a rare genetic condition?
Yes. Mandibulofacial dysostosis with microcephaly (MFDM) is a rare disorder but its exact prevalence is not known. More than 60 affected people have been reported to date in the medical literature.
[1][2] In the United States, a rare disease is generally considered to be a disease that affects fewer than 200,000 people.
Last updated: 7/27/2015
Are there any other names for mandibulofacial dysostosis with microcephaly?
There are several names and acronyms that have been used to describe mandibulofacial dysostosis with microcephaly, depending on the source. These include:
- Mandibulofacial dysostosis, Guion-Almeida type
- Mandibulofacial dysostosis-microcephaly syndrome
- Growth delay - intellectual disability - mandibulofacial dysostosis - microcephaly - cleft palate
- MFDGA
- MFDM
Last updated: 7/27/2015
What are the signs and symptoms of mandibulofacial dysostosis with microcephaly?
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
What causes mandibulofacial dysostosis with microcephaly?
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
How is mandibulofacial dysostosis with microcephaly inherited?
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
How might mandibulofacial dysostosis with microcephaly be treated?
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
Where can I find additional information about mandibulofacial dysostosis with microcephaly?
You can find relevant articles on mandibulofacial dysostosis with microcephaly (MFDM) through
PubMed, a searchable database of biomedical journal articles. Although not all of the articles are available for free online, most articles listed in PubMed have a summary available. To obtain the full article, contact a medical/university library or your local library for interlibrary loan. You can also order articles online through the publisher’s Web site. Using "mandibulofacial dysostosis with microcephaly" as your search term should help you locate articles. Use the advanced search feature to narrow your search results.
Click here to view a sample search of articles about MFDM.
The National Library of Medicine (NLM) Web site has a page for locating libraries in your area that can provide direct access to these journals (print or online). The Web page also describes how you can get these articles through interlibrary loan and Loansome Doc (an NLM document-ordering service). You can access this page at the following link
http://nnlm.gov/members. You can also contact the NLM toll-free at 888-346-3656 to locate libraries in your area.
Last updated: 7/30/2015
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