Muenke syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Muenke syndrome is a condition characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face.

Many people with this disorder have a premature fusion of skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may also be malformed. These changes can result in an abnormally shaped head, wide-set eyes, and flattened cheekbones. About 5 percent of affected individuals have an enlarged head (macrocephaly). People with Muenke syndrome may also have mild abnormalities of the hands or feet, and hearing loss has been observed in some cases. Most people with this condition have normal intellect, but developmental delay and learning problems are possible.

The signs and symptoms of Muenke syndrome vary among affected people, and some features overlap with those seen in other craniosynostosis syndromes. A small percentage of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

A particular mutation in the FGFR3 gene causes Muenke syndrome. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. The mutation associated with Muenke syndrome causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should.

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.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Muenke syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 4 percent of all cases of craniosynostosis.

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.

Brachycephaly · Frequent (79-30%)

An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.

Carpal synostosis · Frequent (79-30%)

Synostosis (bony fusion) involving one or more bones of the carpus (scaphoid, lunate, triquetrum, trapezium, trapezoid, capitate, hamate, pisiform).

Cone-shaped epiphysis · Frequent (79-30%)

Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.

Coronal craniosynostosis · Frequent (79-30%)

Premature closure of the coronal suture of skull.

High, narrow palate · Frequent (79-30%)

The presence of a high and narrow palate.

Hypertelorism · Frequent (79-30%)

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

Increased intracranial pressure · Frequent (79-30%)

An increase of the pressure inside the cranium (skull) and thereby in the brain tissue and cerebrospinal fluid.

Malar flattening · Frequent (79-30%)

Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.

Plagiocephaly · Frequent (79-30%)

Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.

Proptosis · Frequent (79-30%)

An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

Ptosis · Frequent (79-30%)

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Sensorineural hearing impairment · Frequent (79-30%)

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

Short foot · Frequent (79-30%)

A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).

Short palm · Frequent (79-30%)

Short palm.

Other findings in the same source

From: Orphanet

Additional reported features include Tarsal synostosis (Frequent (79-30%)); Global developmental delay (Occasional (29-5%)); Hydrocephalus (Occasional (29-5%)); Hypermelanotic macule (Occasional (29-5%)); Macrocephaly (Occasional (29-5%)); Hypopigmentation of hair (Occasional (29-5%)); Hypopigmented skin patches (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 Muenke 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

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Muenke syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

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.