What Is It, Causes, Treatment, and More
Author:Anna Hernández, MD
Editors:Alyssa Haag,Ian Mannarino, MD, MBA,Kelsey LaFayette, DNP, ARNP, FNP-C
Illustrator:Jessica Reynolds, MS
Copyeditor:Stacy Johnson, LMSW
Apert Syndrome: What Is It, Causes, Treatment, and More
Apert syndrome is a rare genetic disorder characterized by premature fusion of the skull bones, also known as craniosynostosis. This prevents the skull from growing and affects the shape of the head and face, causing increased pressure around the brain. In almost all cases, Apert syndrome is associated with other complex malformations, such as the fusion of the fingers and webbing of the fingers and toes. The exact incidence of Apert syndrome is unknown, but it is estimated to occur in about one in 65,000 to 88,000 births.
What causes Apert syndrome?
Apert syndrome is caused by mutations in the gene that codes for the fibroblast growth factor receptor-2 (FGFR2), a protein that plays an essential role in the growth and development of specific cells in the body, including bone cells. It is thought that mutations in the FGFR2 gene may promote the early maturation of bone cells during fetal development, leading to the premature fusion of bones in the skull, hands, and feet. Different mutations in the FGFR2 gene may cause other related disorders, including Pfeiffer syndrome, Crouzon syndrome, and Jackson-Weiss syndrome.In most cases, Apert syndrome results from de novo FGFR2 mutations, meaning they arise spontaneously. It has been reported that these sporadic mutations may be associated with an increased age of the father. More rarely, Apert syndrome can be inherited in an autosomal dominant pattern, meaning only a single copy of the mutated gene is necessary to develop the condition. With autosomal dominant inheritance, there is a 50% chance of passing the condition to the offspring with each pregnancy.
What are the signs and symptoms of Apert syndrome?
The most characteristic sign of Apert syndrome is craniosynostosis, the early fusion of the fibrous membranes between the bones in the skull. During childhood, the unfused cranial sutures allow the infant’s brain to grow and expand without causing an increase in intracranial pressure; however, in individuals with Apert syndrome, closure of the coronal suture causes the top of the skull to develop a cone shape (i.e., acrocephaly) and affect the development of the facial bones. In severe cases, early fusion of the bones in the skull may prevent the brain from growing to its usual size, affecting intellectual development and sometimes causing a build-up of cerebrospinal fluid (CSF) within the skull, known as hydrocephalus.
Most people with Apert syndrome have characteristic facial features, including a high forehead with wide, bulging eyes and a sunken midface. Other eye abnormalities include downward-slanting eyes and eyes that do not look in the same direction. When the mouth closes, the upper jaw tends to lie behind the lower jaw, creating an underbite. There can also be other dental problems, such as missing teeth, delayed dental eruption, malocclusion, and dental crowning. Some children may have cleft palate, which is when the roof of the mouth has an opening into the nasal cavity. Because of these malformations, individuals with Apert syndrome may have problems with feeding and breathing, like obstructive sleep apnea.Another characteristic feature of Apert syndrome is syndactyly, which refers to the fusion or webbing of the fingers and toes. Many individuals have a complete fusion of the three middle fingers; however, the thumb and fifth fingers may also be involved.
People with Apert syndrome can have varying developmental delays, though most individuals present with normal cognitive development or mild intellectual disability. Additional signs and symptoms can include short stature; neurological and skeletal malformations (e.g., the fusion of the vertebrae and other bones); and hearing loss and frequent ear infections. Only a small percentage of individuals have malformations in other organ systems, including cardiac defects, gastrointestinal malformations, and genitourinary tract anomalies.
How is Apert syndrome diagnosed?
Apert syndrome is usually diagnosed at birth or during infancy based on the characteristic shape of the skull and skeletal defects involving the hands and feet. Prenatal diagnosis can be achieved by identifying its distinctive features on a prenatal ultrasound or genetic testing. Additional tests, such as X-rays, a CT scan, or MRI, may be conducted to further assess the skull's shape and plan appropriate treatment. In cases where the diagnosis is uncertain, molecular genetic testing may be performed.
How is Apert syndrome treated?
Treatment of Apert syndrome differs for every individual and depends on their signs and symptoms. Because of its complexity, syndrome treatment is often performed at specialized craniofacial centers by a team of healthcare providers, including pediatricians and surgeons.
Treatment focuses on correcting the early fusion of the skull, which a series of surgical procedures can achieve. The first surgery is typically performed during the first year of life and involves releasing the bones in the skull so that the brain has space to develop normally. If hydrocephalus is present, a ventriculoperitoneal (VP) shunt, which connects the brain's ventricular system to the peritoneal cavity in the abdomen, can be used to allow cerebrospinal fluid to drain out and reduce the intracranial pressure. Since bone grows during childhood and adolescence, further surgeries may be needed to correct skull and facial deformities. In addition, reconstructive surgery may help correct skeletal defects involving other body parts, like the hands and feet.Further treatment focuses on treating and preventing secondary complications, including using hearing aids in case of hearing loss; and using lubricating eye drops and ointments to prevent damage to the eye's cornea. Early interventions like speech therapy, occupational therapy, and special education are essential to help children with Apert syndrome reach their full potential. Although life expectancy varies between individuals with Apert syndrome, those who survive past childhood tend to have an average life expectancy.
What are the most important facts to know about Apert syndrome?
Apert syndrome is a rare genetic disorder characterized by early fusion of the bones in the skull and syndactyly of the hands and feet. Distinctive facial features include a broad forehead with wide, big eyes and a sunken midface. Most cases are caused by de novo mutations of the FGFR2 gene, which plays a vital role in skeletal development during fetal development. Diagnosis of Apert syndrome is based on its typical clinical features and can be confirmed by genetic testing. Treatment includes a series of reconstructive surgeries as well as supportive treatment.
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Resources for research and reference
Baby, T. K., Jacob, L. E., Mathew, A., Thomas, N., & Venugopal, L. (n.d.). Apert Syndrome: Revisited. Ompj.org. Retrieved March 22, 2023, from https://ompj.org/files/Article%204-12ae2c263d7e583feafc577390fcb22918802117.pdf
Faraz, F., Garg, A., & Vignesh, R. (2019). Apert syndrome: A case report. Journal of South Asian Association of Pediatric Dentistry, 2(1), 32–34. https://doi.org/10.5005/jp-journals-10077-3019
Fernandes, M. B. L., Maximino, L. P., Perosa, G. B., Abramides, D. V. M., Passos-Bueno, M. R., & Yacubian-Fernandes, A. (2016). Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects. American Journal of Medical Genetics. Part A, 170(6), 1532–1537. https://doi.org/10.1002/ajmg.a.37640
Koca, T. T. (2016). Apert syndrome: A case report and review of the literature. Northern Clinics of Istanbul, 3(2), 135–139. https://doi.org/10.14744/nci.2015.30602
Wenger, T. L., Hing, A. V., & Evans, K. N. (2019). Apert Syndrome. University of Washington, Seattle.