Burn-McKeown syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Burn-McKeown syndrome is a disorder that is present from birth (congenital) and involves abnormalities of the nasal passages, characteristic facial features, hearing loss, heart abnormalities, and short stature.

In people with Burn-McKeown syndrome, both nasal passages are usually narrowed (bilateral choanal stenosis) or completely blocked (bilateral choanal atresia), which can cause life-threatening breathing problems in infancy without surgical repair. Typical facial features include narrow openings of the eyelids (short palpebral fissures); a gap (coloboma) in the lower eyelids; widely spaced eyes (hypertelorism); a prominent bridge of the nose; a short space between the nose and the upper lip (philtrum); a small opening of the mouth (microstomia); and large, protruding ears.

Some people with Burn-McKeown syndrome have congenital hearing loss in both ears which varies in severity among affected individuals. The hearing loss is described as mixed, which means that it is caused by both changes in the inner ear (sensorineural hearing loss) and changes in the middle ear (conductive hearing loss).

Other features that can occur in Burn-McKeown syndrome include mild short stature and congenital heart defects such as patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Intelligence is unaffected in Burn-McKeown syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Burn-McKeown syndrome is caused by mutations in the TXNL4A gene or in an area of genetic material near the TXNL4A gene called the promoter region, which controls the production of protein from the gene. The TXNL4A gene provides instructions for making one part (subunit) of a protein complex called the major spliceosome, which is the larger of two types of spliceosomes found in human cells. Spliceosomes help process messenger RNA (mRNA), which is a chemical cousin of DNA that serves as a genetic blueprint for making proteins. Spliceosomes recognize and then remove regions called introns from immature mRNA molecules to help produce mature mRNA.

The mutations affecting the TXNL4A gene that cause Burn-McKeown syndrome reduce the amount of protein produced from the gene. Research suggests that reduced quantities of this spliceosome subunit affect the assembly of the major spliceosome and change the production of a particular group of mRNA molecules. The details of these changes and their relationship to the specific signs and symptoms of Burn-McKeown syndrome are unknown. However, mutations in several genes involved in spliceosome formation or function have been shown to cause other conditions with abnormalities affecting the head and face (craniofacial malformations), so craniofacial development is thought to be particularly sensitive to spliceosome problems.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Burn-McKeown syndrome is a rare disorder; its prevalence is unknown. Only a small number of affected individuals have been described in the medical literature.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Bilateral choanal atresia · Very frequent (99-80%)

Bilateral absence (atresia) of the posterior nasal aperture (choana).

Hypertelorism · Very frequent (99-80%)

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Short palpebral fissure · Very frequent (99-80%)

Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.

Abnormal cardiac septum morphology · Frequent (79-30%)

An anomaly of the intra-atrial or intraventricular septum.

Prominent nasal bridge · Frequent (79-30%)

Anterior positioning of the nasal root in comparison to the usual positioning for age.

Abnormal palate morphology · Occasional (29-5%)

Any abnormality of the palate, i.e., of roof of the mouth.

Abnormality of the eye · Occasional (29-5%)

Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Abnormality of vision · Occasional (29-5%)

Abnormality of eyesight (visual perception).

Other findings in the same source

From: Orphanet

Additional reported features include Short nose (Occasional (29-5%)); Short stature (Occasional (29-5%)); Wide nasal bridge (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Burn-McKeown syndrome 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.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

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.