Apert syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Apert syndrome is a genetic disorder characterized by skeletal abnormalities. A key feature of Apert syndrome is the premature closure of the bones of the skull (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. In addition, a varied number of fingers and toes are fused together (syndactyly).

Craniosynostosis causes many of the characteristic facial features of Apert syndrome. Premature fusion of the skull bones prevents the head from growing normally, which leads to a sunken appearance in the middle of the face (midface hypoplasia), a beaked nose, a wrinkled forehead, and an opening in the roof of the mouth (a cleft palate). In individuals with Apert syndrome, an underdeveloped upper jaw can lead to dental problems, such as missing teeth, irregular tooth enamel, and crowded teeth.

Many individuals with Apert syndrome have vision problems due to eye abnormalities, which can include bulging eyes (exophthalmos), wide-set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), eyes that do not look in the same direction (strabismus), and shallow eye sockets (ocular proptosis). Some people with Apert syndrome have hearing loss or recurrent ear infections due to malformed ear structures.

Abnormal development of structures in the face and head can also cause partial blockage of the airways and lead to breathing difficulties in people with Apert syndrome. Craniosynostosis also affects development of the brain, which can disrupt intellectual development. Cognitive abilities in people with Apert syndrome range from normal to mild or moderate intellectual disability.

Individuals with Apert syndrome have syndactyly of the fingers and toes. The severity of the fusion varies, although the hands tend to be more severely affected than the feet. Most commonly, three digits on each hand and foot are fused together. In the most severe cases, all of the fingers and toes are fused. Rarely, people with Apert syndrome may have extra fingers or toes (polydactyly). Some people with Apert syndrome have abnormalities in the bones of the elbows or shoulders. These bone problems can restrict movement and impede everyday activities. In some people, abnormalities occur in both sides of the body, but in others, only one side is affected.

Additional signs and symptoms of Apert syndrome can include unusually heavy sweating (hyperhidrosis), oily skin with severe acne, or patches of missing hair in the eyebrows.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in a gene known as FGFR2 cause Apert syndrome. This gene provides instructions for making a protein called fibroblast growth factor receptor 2 (FGFR2). Among its multiple functions, the FGFR2 protein plays a key role in development before birth by signaling immature cells to become bone cells. A mutation in a specific part of the FGFR2 gene alters the protein, increasing its signaling. The abnormal signaling causes the cell to mature too quickly and promotes the premature fusion of bones in the skull, hands, and feet.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Apert syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Nearly all cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Apert syndrome affects an estimated 1 in 65,000 to 88,000 newborns.

Although parents of all ages can have a child with Apert syndrome, the risk is increased in older fathers.

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.

Acrobrachycephaly · Very frequent (99-80%)

An abnormality of head shape characterized by the presence of a short, wide head as well as a pointy or conical form of the top of the head owing to premature closure of the coronal and lambdoid sutures.

Brachyturricephaly · Very frequent (99-80%)

Abnormal vertical height of the skull and a shortening of its anterior-posterior length, frequently combined with malformations of the occipital region.

Broad forehead · Very frequent (99-80%)

Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.

Conductive hearing impairment · Very frequent (99-80%)

An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.

Coronal craniosynostosis · Very frequent (99-80%)

Premature closure of the coronal suture of skull.

Craniosynostosis · Very frequent (99-80%)

Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.

Depressed nasal bridge · Very frequent (99-80%)

Posterior positioning of the nasal root in relation to the overall facial profile for age.

Finger syndactyly · Very frequent (99-80%)

Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers in a proximo-distal axis are referred to as "Symphalangism".

Other findings in the same source

From: Orphanet

Additional reported features include Flat face (Very frequent (99-80%)); Frontal bossing (Very frequent (99-80%)); Hypoplasia of the maxilla (Very frequent (99-80%)); Proptosis (Very frequent (99-80%)); Toe syndactyly (Very frequent (99-80%)); Absent septum pellucidum (Frequent (79-30%)); Agenesis of corpus callosum (Frequent (79-30%)); Aplasia/Hypoplasia of the thumb (Frequent (79-30%)); Broad thumb (Frequent (79-30%)); Cervical vertebrae fusion (C5/C6) (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Apert 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 Apert 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.