Mandibulofacial dysostosis with microcephaly

(often shortened to MFDM)

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Reviewed September 2014

What is MFDM?

Mandibulofacial dysostosis with microcephaly (MFDM) is a disorder that causes abnormalities of the head and face. People with this disorder often have an unusually small head at birth, and the head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Affected individuals have developmental delay and intellectual disability that can range from mild to severe. Speech and language problems are also common in this disorder.

Facial abnormalities that occur in MFDM include underdevelopment of the middle of the face and the cheekbones (midface and malar hypoplasia) and an unusually small lower jaw (mandibular hypoplasia, also called micrognathia). The external ears are small and abnormally shaped, and they may have skin growths in front of them called preauricular tags. There may also be abnormalities of the ear canal, the tiny bones in the ears (ossicles), or a part of the inner ear called the semicircular canals. These ear abnormalities lead to hearing loss in most affected individuals. Some people with MFDM have an opening in the roof of the mouth (cleft palate), which may also contribute to hearing loss by increasing the risk of ear infections. Affected individuals can also have a blockage of the nasal passages (choanal atresia) that can cause respiratory problems.

Heart problems, abnormalities of the thumbs, and short stature are other features that can occur in MFDM. Some people with this disorder also have blockage of the esophagus (esophageal atresia). In esophageal atresia, the upper esophagus does not connect to the lower esophagus and stomach. Most babies born with esophageal atresia (EA) also have a tracheoesophageal fistula (TEF), in which the esophagus and the trachea are abnormally connected, allowing fluids from the esophagus to get into the airways and interfere with breathing. Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a life-threatening condition; without treatment, it prevents normal feeding and can cause lung damage from repeated exposure to esophageal fluids.

How common is MFDM?

MFDM is a rare disorder; its exact prevalence is unknown. More than 60 affected individuals have been described in the medical literature.

What genes are related to MFDM?

MFDM is caused by mutations in the EFTUD2 gene. This gene provides instructions for making one part (subunit) of two complexes called the major and minor spliceosomes. Spliceosomes help process messenger RNA (mRNA), which is a chemical cousin of DNA that serves as a genetic blueprint for making proteins. The spliceosomes recognize and then remove regions called introns to help produce mature mRNA molecules.

EFTUD2 gene mutations that cause MFDM result in the production of little or no functional enzyme from one copy of the gene in each cell. A shortage of this enzyme likely impairs mRNA processing. The relationship between these mutations and the specific symptoms of MFDM is not well understood.

How do people inherit MFDM?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from a parent. The parent may be mildly affected or may be unaffected. Sometimes the parent has the gene mutation only in some or all of their sperm or egg cells, which is known as germline mosaicism. In these cases, the parent has no signs or symptoms of the condition.

Where can I find information about diagnosis or management of MFDM?

These resources address the diagnosis or management of MFDM and may include treatment providers.

You might also find information on the diagnosis or management of MFDM in Educational resourcesand Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about MFDM?

You may find the following resources about MFDM helpful. These materials are written for the general public.

MedlinePlus - Health information (3 links)
Additional NIH Resources - National Institutes of Health
National Institute of Neurological Disorders and Stroke: Microcephaly Information Page
Educational resources - Information pages (2 links)
Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Gene Reviews - Clinical summary
Genetic Testing Registry - Repository of genetic test information (1 link)
OMIM - Genetic disorder catalog

What other names do people use for MFDM?

mandibulofacial dysostosis, Guion-Almeida type
MFDGA

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about MFDM?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding MFDM?

atresia ; autosomal ; autosomal dominant ; cell ; cleft palate ; developmental delay ; disability ; DNA ;egg ; enzyme ; esophagus ; fistula ; gene ; germline ; germline mosaicism ; hypoplasia ; inherited ;lower jaw ; mental retardation ; messenger RNA ; microcephaly ; micrognathia ; mosaicism ; mRNA ;mutation ; palate ; preauricular ; prevalence ; respiratory ; RNA ; short stature ; sperm ; stature ;stomach ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (6 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.