Mandibulofacial dysostosis with microcephaly

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

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.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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

Which doctor should you see?

The suggested department for discussing Mandibulofacial dysostosis with microcephaly is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.