Changing Faces, Changing Lives
Crouzon Syndrome
Contents
What is Crouzon Syndrome?
Crouzon syndrome: is a genetic condition characterized by craniosynostosis (premature fusion of skull bones), which affects the shape of the head and face.
Otherwise known as?
Craniofacial dysostosis
Signs & Symptoms
The severity of symptoms varies among individuals.
1. Craniofacial differences
- Craniosynostosis: Premature skull fusion leading to:
- a short, wide, or tall skull (brachycephaly).
- a bulging forehead (frontal bossing).
- Shallow Eye Sockets (ocular proptosis):
- bulging or protruding eyes.
- eyes may appear widely spaced (hypertelorism).
- Midface Hypoplasia:
- underdeveloped upper jaw (maxilla), giving a flat midface appearance.
- possible breathing and feeding difficulties.
- Beaked Nose: A nose with a narrow and pointed appearance.
- Dental Problems:
- Crowded, misaligned, or missing teeth.
- High-arched or cleft palate in some cases.
2. Vision Problems
- Strabismus (Crossed or Misaligned Eyes).
- Exposure Keratitis (damage to the cornea due to bulging eyes).
- Optic Nerve Compression (can lead to vision loss in severe cases).
3. Hearing and Ear Issues
- Frequent ear infections due to structural anomalies in the ear.
- Possible hearing loss (conductive or sensorineural).
4. Neurological Symptoms
- Increased Intracranial Pressure (ICP): Due to fusion of the bones in the skull restricting brain growth. Symptoms may include:
- Headaches
- Vomiting
- Irritability
- Hydrocephalus (in some cases): Excess cerebrospinal fluid build-up in the brain.
5. Intellectual Development
- Normal Intelligence: Most individuals have typical cognitive development.
- Learning Difficulties (occasionally): If complications like increased intracranial pressure or hydrocephalus occur.
Causes
Apert syndrome is caused by mutations in the FGFR2 (Fibroblast Growth Factor Receptor 2) gene. This gene plays a crucial role in regulating bone development and growth, particularly in the skull, hands, and feet.
Causes of Apert Syndrome:
- Genetic Mutation:
- Apert syndrome results from a spontaneous (de novo) mutation in the FGFR2 gene, meaning it usually occurs randomly during early foetal development without being inherited from parents.
- In rare cases, it can be inherited in an autosomal dominant pattern, meaning a parent with the mutation has a 50% chance of passing it on to their child.
- Effect of the Mutation:
- The FGFR2 mutation causes the premature fusion of skull bones (craniosynostosis), leading to differences in skull and facial development.
- It also affects limb development, leading to webbed or fused fingers and toes (syndactyly).
While the exact reason why a mutation occurs spontaneously is often not fully understood, it is known to be a rare genetic event.
Mechanism (the how)
A baby’s skull is made of several plates joined by flexible seams called sutures, and deeper growth plates in the skull base.
In Crouzon, a growth-signal pathway (controlled by genes FGFR2/FGFR3) is over-active.
This over-signalling makes bone-forming cells around some sutures mature and lock too early, so those seams turn into solid bone sooner than they should.
Once a suture closes, growth in that direction stops and growth is redirected to areas that remain open.
The same over-signalling also alters how the skull base growth plates develop, changing the forward growth pattern of the face.
These changes begin early in foetal development and then shape skull and facial growth over time.
Causes (the why)
Crouzon syndrome is a genetic condition caused by mutations in the FGFR2 (fibroblast growth factor receptor 2) gene and, in rare cases, the FGFR3 gene. These genes play a role in bone growth and development during foetal development.
1. Genetic Mutation
- The FGFR2 mutation causes the early fusion of skull bones (craniosynostosis), leading to the characteristic facial and skull differences of Crouzon syndrome.
- In rare cases, FGFR3 mutations may also be involved, sometimes leading to a variant form called ‘Crouzon syndrome with acanthosis nigricans’ (which includes dark, velvety patches on the skin, usually in areas like the neck and armpits).
- Inherited (autosomal dominant):
- A child has a 50% chance of inheriting the condition if one parent has Crouzon syndrome.
- Spontaneous (De Novo) Mutation:
- In about 50% of cases, the mutation occurs randomly in a baby with no family history of the condition.
Crouzon syndrome is not caused by environmental factors or anything a mother does during pregnancy. It is purely genetic.
Testing & Diagnosis
Crouzon syndrome is typically diagnosed through a combination of physical examination, genetic testing, and imaging studies. Early diagnosis allows for better management and treatment of symptoms.
1. Physical examination
- Clinical evaluation is usually the first step. A doctor will examine the child’s features for characteristic signs, such as:
- Craniosynostosis: Premature fusion of skull bones leading to a difference in head shape.
- Protruding eyes (ocular proptosis) due to shallow eye sockets.
- Midface hypoplasia (underdeveloped upper jaw, leading to a flat face).
- Beaked nose and other facial differences.
- Dental problems, including misaligned or crowded teeth.
2. Genetic Testing
- FGFR2 gene mutation testing can confirm the diagnosis.
- This test involves analysing a blood sample to detect mutations in the FGFR2 gene, which is the most common cause of Crouzon syndrome.
- In some cases, mutations in the FGFR3 gene may also be involved.
- Genetic counselling may be recommended to discuss inheritance risks and recurrence in future pregnancies.
3. Imaging Studies
- X-rays or CT Scans of the skull are used to:
- Assess the fusion of skull bones (craniosynostosis).
- Identify any differences in the shape of the skull and face.
- Determine the extent of brain involvement, such as hydrocephalus or increased intracranial pressure.
- MRI (Magnetic Resonance Imaging) may be used to:
- Examine the brain for any associated conditions like hydrocephalus or brain compression.
- Evaluate optic nerve function to assess potential vision problems or nerve damage.
4. Additional Tests
- Hearing and vision tests may be conducted to identify issues such as hearing loss or vision problems due to craniofacial differences.
- Cognitive and developmental assessments might be performed if there are concerns about learning or developmental delays, although intelligence is typically normal in most individuals with Crouzon syndrome.
Prevalence
In Australia, approximately 2 babies in 100,000 births are diagnosed with Crouzon syndrome.
Reference: Junaid, M., Slack-Smith, L., Wong, K., Bourke, J., Baynam, G., Calache, H., & Leonard, H. (2022). Epidemiology of Rare Craniofacial Anomalies: Retrospective Western Australian Population Data Linkage Study. The Journal of Pediatrics, 241, 162-172.e169. https://doi.org/10.1016/j.jpeds.2021.09.060
Did you know?
Crouzon syndrome was the first identified genetic syndrome linked to craniosynostosis and was originally described in both a mother and daughter by a French physician, Octave Crouzon, in 1912.
Additional references
David, D. J., & Sheen, R. (1990). Surgical correction of Crouzon syndrome. Plastic and reconstructive surgery, 85(3), 344-354.
Proudman, T. W., Moore, M. H., Abbott, A. H., & David, D. J. (1994). Noncraniofacial manifestations of Crouzon disease. J Craniofac Surg, 5(4), 218-222.
This information is based on the expertise of clinicians who work with families affected by craniofacial conditions and the lived experience of parents with children who have been diagnosed with craniosynostosis. We thank everyone who contributed to this fact sheet.
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