Craniofacial conditions
Apert Syndrome
Syndromic craniosynostosis with multi-suture fusion, midface hypoplasia and syndactyly of the hands and feet.
Apert syndrome is a rare congenital craniofacial condition. Typical features are premature fusion of several cranial sutures, underdevelopment of the midface and complex fusions of fingers and toes. The expression varies greatly between individuals. Many children therefore need lifelong care from a specialised interdisciplinary centre.
Cause and inheritance
Apert syndrome is almost always caused by a change in the FGFR2 gene (fibroblast growth factor receptor 2) – in more than 98 % of cases by two specific point mutations (p.Ser252Trp or p.Pro253Arg).[1] This gene influences the growth and maturation of bone and tissue.
In most cases the change arises de novo, i.e. without a parent being affected. If an affected person has children themselves, there is a 50 % risk at each pregnancy of passing on the genetic change (autosomal dominant inheritance). It occurs in about 1 in 65,000–70,000 births.[1]
Typical features
Frequent findings are:
- Premature closure of several cranial sutures, especially the coronal sutures
- High or tower-shaped skull, broad forehead, altered head shape
- Shallow eye sockets with protruding eyes (exophthalmos)
- Underdevelopment of the midface
- Narrow upper airways, snoring or sleep apnoea
- High palate, sometimes cleft palate
- Dental malpositions, crowding, delayed tooth eruption
- Fusions of fingers and toes (syndactyly), usually bilateral
- Recurrent middle-ear problems or hearing loss
- Possible developmental, speech or learning differences
Not every child has all features. Individual assessment is decisive.
Why early assessment is important
In Apert syndrome, medically relevant problems can arise early: raised intracranial pressure, airway narrowing, sleep apnoea, corneal risk from incomplete eyelid closure, feeding problems, hearing loss and limitations of hand function. Early presentation at a craniofacial centre is therefore important — there, the skull, brain, eyes, airways, ears, jaws, teeth, hands, feet, speech and development are assessed together.
Craniofacial procedures
Craniofacial surgery is a central component of treatment. The aim is not only to improve head shape but above all to protect the brain, eyes, breathing and development.
1. Skull and skull-base surgery in infancy
Many children have multi-suture synostosis with restricted skull growth. Possible goals of early surgery are more room for the growing brain, lowering or preventing raised intracranial pressure, improving head shape, protecting the orbital region and reducing further sequelae. Depending on the findings, various techniques are possible: posterior cranial vault expansion, distraction osteogenesis of the posterior vault or fronto-orbital advancement.
2. Fronto-orbital correction
A fronto-orbital operation concerns the forehead and upper orbital rim. It may be necessary when forehead and orbit shape, eye protection or intracranial space require it. In Apert syndrome, careful consideration is needed as to which technique provides the greatest benefit and at which time.
3. Midface advancement
Many children have a markedly underdeveloped midface, which can lead to breathing problems, sleep apnoea, lack of eyelid protection, protruding eyes, malocclusion and functional limitations. Possible techniques are:
- Le Fort III osteotomy: advancement of the midface, cheekbones and upper jaw portion
- Monobloc advancement: joint advancement of forehead-orbit-midface
- Distraction osteogenesis: slow, controlled advancement over several weeks
Midface surgery may be needed earlier for functional reasons (e.g. severe sleep apnoea or threatened cornea); it is often performed in later childhood.
4. Orthodontics and orthognathic surgery
In adolescence, further orthodontic and jaw-surgical measures may become necessary. There is often a class III malocclusion, crossbite, dental crowding and a high palate. Definitive jaw repositioning is usually planned only after growth is largely complete.
Airways and sleep apnoea
Children with Apert syndrome have an increased risk of obstructive sleep apnoea. Causes are midface hypoplasia, narrow nasal passages, enlarged adenoids or tonsils as well as jaw malposition. The frequency of sleep apnoea in syndromic craniosynostosis lies between 7 % and 67 %.[2]
Warning signs: loud snoring, breathing pauses during sleep, restless sleep, daytime sleepiness, failure to thrive, morning headaches.
Eyes
Because of shallow eye sockets, the eyes may protrude. This carries a risk of corneal drying, corneal injuries, squint (strabismus in up to 50 % of cases),[3] refractive error, amblyopia and optic nerve damage with raised intracranial pressure. Regular ophthalmological checks are necessary, especially in infancy and early childhood.
Hands and feet
The fusion of the fingers in Apert syndrome is usually complex. The aim of hand surgery is the best possible grip function, thumb function and independence in daily life. Several operations are often necessary. The first hand operation is often planned in the first year of life. Occupational therapy, scar care and long-term functional monitoring are important. Foot operations are less often functionally imperative.
Hearing, speech and development
Middle-ear effusions and hearing loss are common. Hearing tests should therefore be carried out regularly. Speech therapy can help with language development, palate function, articulation and eating/swallowing issues. Early support, developmental assessment and educational support are useful depending on the course. The developmental spectrum is broad – from normal intelligence to learning differences.
Diagnostics
The work-up includes, depending on age and situation: clinical examination by a craniofacial team, genetic testing of the FGFR2 gene, 3D imaging of the skull, ophthalmological examination, sleep diagnostics if airway problems are suspected, ENT examination and hearing test, dental and orthodontic assessment, hand and foot diagnostics, and developmental and speech 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, hand surgery, speech therapy, physiotherapy and occupational 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
- Rapid deterioration of the eyes, corneal clouding or incomplete eyelid closure
- Seizures
- Fever or wound problems after operations
- Marked feeding weakness or failure to thrive
Prognosis
Many children with Apert syndrome develop well with specialised treatment and can lead an active life. The prognosis depends strongly on the airway situation, intracranial pressure, eye findings, hearing, developmental support, hand function and the quality of long-term interdisciplinary care. Apert syndrome is complex, but many problems can be detected early and treated in a targeted way.
References
- Wilkie AO et al. (1995). Apert syndrome results from localized mutations of FGFR2. Nat Genet, 9(2):165–72. 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
- 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
- Renier D et al. (2000). Management of craniosynostoses. Childs Nerv Syst, 16(10–11):645–58. DOI