By: Catherine Joachin
What is Apert syndrome?
Apert syndrome is a congenital disease characterized by craniofacial abnormalities and premature fusions of coronal joints, fingers, and toes (Cleveland Clinic, 2021). This disorder is caused by genetic mutations in the fibroblast growth factor receptor-2 (FGFR2), a chromosome 10 gene responsible for bone development (Children’s Hospital Colorado, n.d.). Other medical conditions marked by skull malformations are linked to FGFR2 mutations, including Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Saethre-Chotzen syndrome (Azoury et al., 2017).
Signs and Symptoms
The most apparent symptoms that, combined, differentiate Apert syndrome from other disorders include:
• Early closure of skull sutures (craniosynostosis)
• Underdevelopment of central face area (midface hypoplasia)
• Webbing of fingers and toes (syndactyly)
These characteristics may cause the individual’s head to appear elongated and prominently pointed, their forehead broader, their eyes widely spaced and downward slanted, their nose flat and their mouth left without a roof (cleft palate) (Cleveland Clinic, 2021). These underdeveloped facial features can lead to vision problems, breathing difficulties (e.g. sleep apnea), gastrointestinal issues, hearing loss, and a greater risk of contracting heart disease (Children’s Hospital Colorado, n.d.; National Library of Medicine, 2023). Craniosynostosis can also cause increased pressure inside the skull which could affect cognitive development and lead to intellectual impairment (Cleveland Clinic, 2021).
Diagnosis and Treatment
While statistics vary, Apert syndrome reportedly occurs in 1 out of every 65,000 births, making it a rather rare condition (UPMC Children’s Hospital of Pittsburgh, n.d.). There are no existing prevention methods against Apert syndrome, however, it can be diagnosed before birth with the use of genetic testing (UPMC Children’s Hospital of Pittsburgh, n.d.). Incidence is indifferent to sex, but there is a higher risk of inheriting the condition for individuals with a family history of diagnosis (National Library of Medicine, 2023).
Treatment options include early reconstructive surgical interventions (e.g. cleft palate surgery) to correct bone malformations or facial abnormalities in developing babies, the use of adaptive technology such as breathing machines and hearing aids to alleviate complications brought on by respiratory, auditive, or other difficulties as well as physical, occupational and/or speech therapy, depending on the severity of impairment (Cleveland Clinic, 2021).
How does Apert Syndrome relate to epilepsy?
Epilepsy can manifest itself in atypical presentations of Apert syndrome (Tovetjärn et al, 2012; Spruijt et al., 2015; Zhang et al., 2021). There exist several hypotheses as to the etiology of epilepsy in this population. For instance, in 2015, Spruijt and colleagues speculated that their patient’s epileptic activity was triggered by a local pressure on the brain while Zhang and others (2021) suggested that epileptic seizures were triggered by an infection and a fever in their 1-year-old patient.
Research suggests that conditions caused by FGFR mutations are associated with a greater risk of encountering learning and intellectual difficulties (Stark et al., 2015). A study conducted in Scandinavia also reported increased rates of epilepsy in adults with Apert syndrome (Tovetjärn et al, 2012). Greig and colleagues noted cases of postoperative seizures in participants with Apert syndrome who underwent a bipartition distraction, with two instances where patients had presumably died due to sudden unexpected death in epilepsy (SUDEP).
Summary
Apert syndrome is a rare autosomal dominant disorder caused by a genetic defect. The condition is marked by craniofacial malformations and webbed digits, although abnormal presentations can include epilepsy and cognitive development difficulties. Among other theories, the occurrence of
epileptic seizures in individuals with Apert syndrome hints at a potential relationship between epileptiform brain activity and cranial pressure triggered by craniosynostosis. Symptoms can be diminished with the help of corrective surgery and/or targeted therapy, although it is recommended to contact your child’s healthcare provider to determine which treatment is right for them.
References:
Azoury, S. C., Reddy, S., Shukla, V., & Deng, C.-X. (2017). Fibroblast Growth Factor Receptor 2 ( FGFR2 ) Mutation Related Syndromic Craniosynostosis. International Journal of Biological Sciences, 13(12), 1479–1488. https://doi.org/10.7150/ijbs.22373
Children’s Hospital Colorado (n.d.). Apert Syndrome. Retrieved from https:// www.childrenscolorado.org/conditions-and-advice/conditions-and-symptoms/conditions/apert syndrome/
Cleveland Clinic (2021). Apert Syndrome. Cleveland Clinic. Retrieved from: https:// my.clevelandclinic.org/health/diseases/22077-apert-syndrome#prevention
Conrady, C. D., Patel, B.C., Sharma, S. (2023) Apert Syndrome. National Library of Medicine. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK518993/
Greig, A. V. H., Britto, J. A., Abela, C., Witherow, H., Richards, R., Evans, R. D., Jeelani, N. U. O., Hayward, R. D., & Dunaway, D. J. (2013). Correcting the typical Apert face: combining bipartition with monobloc distraction. Plastic and Reconstructive Surgery (1963), 131(2), 219e– 230e. https://doi.org/10.1097/PRS.0b013e3182778882
Spruijt, B., Rijken, B., Joosten, K., Boelhouwer, H., Pullens, B., Lequin, M., Wolvius, E., van Veelen-Vincent, M., & Mathijssen, I. (2015). Atypical presentation of a newborn with Apert syndrome. Child’s Nervous System, 31(3), 481–486. https://doi.org/10.1007/s00381-014-2601-6
Stark, Z., McGillivray, G., Sampson, A., Palma-Dias, R., Edwards, A., Said, J. M., Whiteley, G., & Fink, A. M. (2015). Apert syndrome: temporal lobe abnormalities on fetal brain imaging: Apert syndrome: temporal lobe abnormalities. Prenatal Diagnosis, 35(2), 179–182. https:// doi.org/10.1002/pd.4515
Tovetjärn, R., Tarnow, P., Maltese, G., Fischer, S., Sahlin, P.-E., & Kölby, L. (2012). Children with Apert syndrome as adults: a follow-up study of 28 Scandinavian patients. Plastic and Reconstructive Surgery (1963), 130(4), 572e–576e. https://doi.org/10.1097/ PRS.0b013e318262f355
UPMC Children’s Hospital of Pittsburgh (n.d.). Apert Syndrome. UPMC Children’s Hospital of Pittsburgh. Retrieved from https://www.chp.edu/our-services/plastic-surgery/conditions/apert syndrome
Zhang, Y., Ichinose, F., Maeda, T., Nakamura, T., & Matsuo, M. (2021). A pediatric case of transient periictal MRI abnormalities after repeated seizures. Brain & Development (Tokyo. 1979), 43(7), 809–813. https://doi.org/10.1016/j.braindev.2021.04.001
