Craniofacial conditions
Crouzon Syndrome
The most common syndromic craniosynostosis – with exophthalmos, midface hypoplasia and usually normal hands and feet.
Crouzon syndrome is the most common syndromic craniosynostosis (approx. 1:25,000). It is caused by mutations in the FGFR2 gene (more rarely FGFR3) and inherited in an autosomal dominant manner. Typical features are exophthalmos, a flat midface and premature closure of several cranial sutures – without syndactyly (an important difference from Apert syndrome). Intelligence is usually normal as long as there is no raised intracranial pressure.
Cause and inheritance
Crouzon syndrome is in almost all cases caused by mutations in the FGFR2 gene. More rarely, mutations in the FGFR3 gene are detectable (then often associated with acanthosis nigricans, a characteristic skin finding). Inheritance is autosomal dominant – an affected parent has a 50 % risk at each pregnancy of passing on the syndrome. New mutations without family history also occur.
It occurs in about 1 in 25,000 births and is thus one of the most common syndromic craniosynostoses.[1] The expression is very variable, even within a family – from mild changes to severe craniosynostosis.
Typical features
Typical findings in Crouzon syndrome are:
- Premature closure of one or more cranial sutures (coronal suture, lambdoid suture or several)
- Flat or asymmetric skull depending on the affected sutures
- Exophthalmos – protruding eyes due to shallow eye sockets
- Midface hypoplasia – flat midface, recessed cheekbones
- Relative prognathism – seemingly protruding lower jaw due to a recessed upper jaw
- Narrow upper airways, snoring or sleep apnoea
- Dental malpositions (class III malocclusion), crowding
- Normal hands and feet – important distinguishing feature from Apert syndrome
- Intelligence usually normal, as long as there is no raised intracranial pressure
Why early assessment is important
In Crouzon syndrome too, serious problems can arise early: raised intracranial pressure (a relevant risk in multi-suture synostosis), airway narrowing, sleep apnoea, corneal risk from incomplete eyelid closure, hearing loss and visual deterioration. The craniosynostosis can increase over time – regular checks are therefore important even without an immediate surgical indication.[2]
Early presentation at a craniofacial centre allows a holistic assessment of the skull, brain, eyes, airways, ears, jaws and teeth.
Craniofacial procedures
The surgical priorities depend on the severity, the affected sutures, the intracranial pressure, the eye situation and the airway situation.
1. Skull decompression / vault expansion
When intracranial pressure is raised or skull growth is restricted, an operation to expand the skull volume is indicated. Possible techniques are posterior cranial vault expansion (often with distraction) or a fronto-orbital advancement. In a comparative study from two centres (Great Ormond Street, Seattle Children's) with Apert and Crouzon patients, all three techniques (PCVR = posterior cranial vault remodelling, PVDO = posterior vault distraction, SAPVE = spring-assisted expansion) showed comparable results for skull volume increase.[3]
2. Fronto-orbital correction
A fronto-orbital operation improves the forehead shape and orbital rim and protects the eyes. It is particularly relevant in pronounced exophthalmos and risk to the cornea.
3. Midface advancement
Many affected people have a markedly recessed midface. When this leads to breathing problems, sleep apnoea, lack of eyelid protection, corneal risk or malocclusion, a midface advancement may be indicated. Possible techniques:
- Le Fort III osteotomy: advancement of the midface and cheekbones
- Monobloc advancement: joint advancement of forehead-orbit-midface
- Distraction osteogenesis: slow advancement over weeks, allowing greater distances
In Crouzon syndrome, midface surgery may sometimes be needed earlier for functional reasons (breathing, eyes). However, it is often planned in later childhood or adolescence, when growth and occlusion can be assessed better.
4. Orthodontics and orthognathic surgery
Class III malocclusion, crossbite and dental crowding are common. Definitive orthodontic-surgical treatment is usually planned after growth is largely complete. Regular orthodontic checks from childhood are important.
Airways and sleep apnoea
Children with Crouzon syndrome have an increased risk of obstructive sleep apnoea due to midface hypoplasia and narrow nasal passages. The frequency of sleep apnoea in syndromic craniosynostosis lies between 7 % and 67 %.[4]
Warning signs: loud snoring, breathing pauses during sleep, restless sleep, daytime sleepiness, failure to thrive, morning headaches.
Eyes
Eye involvement is particularly relevant in Crouzon syndrome. Because of shallow eye sockets the eyes protrude (exophthalmos). Consequences may be: corneal drying, corneal injuries with incomplete eyelid closure, squint (strabismus) in about 52 % of cases,[5] astigmatism (approx. 43 %), amblyopia and optic nerve damage with raised intracranial pressure.
Regular ophthalmological checks are mandatory, especially in infancy and early childhood. Parents should seek medical help immediately in case of redness, pain, clouding of the cornea, light sensitivity, increasing protrusion of the eyes or incomplete eyelid closure.
Hearing
Middle-ear effusions and hearing loss are common in Crouzon syndrome. Annual ENT examinations are recommended.[4] Untreated hearing loss can affect language development and learning.
Development and intelligence
Unlike Apert syndrome, intelligence in Crouzon syndrome is usually normal, as long as there is no persistently raised intracranial pressure. Early normalisation of intracranial pressure through skull surgery is therefore important for the cognitive prognosis. School and learning support may nevertheless be useful in individual cases.
Diagnostics
The work-up includes, depending on age and situation: clinical examination by a craniofacial team, genetic testing of the FGFR2 gene (and FGFR3 if needed), 3D imaging of the skull, ophthalmological examination, intracranial pressure measurement if suspected, sleep diagnostics, ENT examination and hearing test, and dental and orthodontic assessment.
Treatment in an interdisciplinary centre
Ideal is care by a specialised team including: oral and maxillofacial / craniofacial surgery, neurosurgery, paediatrics, anaesthesia and intensive care, ophthalmology, ENT and sleep medicine, orthodontics and paediatric dentistry, speech therapy, genetics, psychology and social counselling.
Possible treatment roadmap
When immediate medical help is needed
- Breathing pauses, bluish discolouration or severe respiratory distress
- Increasing drowsiness, vomiting, headaches or unusual irritability (possible signs of raised intracranial pressure)
- Rapid deterioration of the eyes, corneal clouding or incomplete eyelid closure
- Seizures
- Fever or wound problems after operations
Prognosis
With specialised treatment, many affected people can lead an active life. Intelligence is usually normal. The prognosis depends strongly on intracranial pressure control, the airway situation, eye protection and the quality of long-term interdisciplinary care. Crouzon syndrome is variable in its expression – even within a family – and therefore requires individual treatment planning.
References
- Flores-Sarnat L (2002). New insights into craniosynostosis. Semin Pediatr Neurol, 9(4):274–91. DOI
- Renier D et al. (2000). Management of craniosynostoses. Childs Nerv Syst, 16(10–11):645–58. DOI
- Breakey RWF et al. (2023). Two-Center Review of Posterior Vault Expansion following Crouzon and Apert Craniosynostosis. Plast Reconstr Surg, 151(3):615–626. DOI
- Couloigner V, Ayari Khalfallah S (2019). Craniosynostosis and ENT. Neurochirurgie, 65(5):318–321. DOI
- Rostamzad P et al. (2022). Prevalence of Ocular Anomalies in Craniosynostosis. J Clin Med, 11(4):1060. DOI