What Is It, Causes, Signs and Symptoms, and More
Author:Anna Hernández, MD
Editors:Alyssa Haag,Emily Miao, PharmD,Kelsey LaFayette, DNP, ARNP, FNP-C
Illustrator:Jessica Reynolds, MS
Copyeditor:Stacy M. Johnson, LMSW
What is Pfeiffer syndrome?
Pfeiffer syndrome is a rare genetic disorder characterized by the premature fusion of the bones of the skull, also known as craniosynostosis. This prevents the skull from growing as usual and affects the shape of the head and face, sometimes causing increased pressure around the brain. Pfeiffer syndrome can be regarded as a spectrum disorder, with signs and symptoms varying from mild in type one to more severe in types two and three.
What causes Pfeiffer syndrome?
Pfeiffer syndrome is caused by mutations in the fibroblast growth factor receptor-1 (FGFR1) and fibroblast growth factor receptor-2 (FGFR2) genes, which play an essential role in the growth and development of specific cells in the body, including bone cells. It is thought that mutations in either of these genes may promote the early maturation of bone cells during fetal development, leading to the premature fusion of bones in the skull, hands, and feet.
Pfeiffer syndrome is an autosomal dominant disorder, meaning only a single copy of the mutated gene is necessary to develop the condition. Children can inherit the mutated gene from either parent or, most commonly, due to a sporadic mutation in the affected individual. Advanced paternal age has been associated with an increased risk of mutations leading to Pfeiffer syndrome.
What are the signs and symptoms of Pfeiffer syndrome?
Children with Pfeiffer syndrome have characteristic facial features due to the early fusion of the bones of the skull, including a wide head and high forehead; underdeveloped midface with small cheekbones (i.e., midface hypoplasia); a small nose with a low nasal bridge; and widely spaced eyes (i.e., ocular hypertelorism). The characteristic shape of the head and face is accompanied by other manifestations, including broad thumbs and big toes, as well as webbing or fusion of the second and third fingers and toes (i.e., syndactyly). In some cases, children with Pfeiffer syndrome may have hearing loss, visual defects, respiratory problems, and learning disabilities or developmental delays, most commonly affecting speech and language.Pfeiffer type one, or classic Pfeiffer syndrome, includes individuals with mild manifestations and is associated with typical neurological development. Those with type one tend to have a good prognosis and average life expectancy. On the other hand, children with type two and type three Pfeiffer syndrome have more severe manifestations and a shortened life expectancy. Type two is characterized by a severe form of craniosynostosis that causes the skull to have a “tri-lobed” appearance, similar to a cloverleaf (i.e., cloverleaf skull deformity). In extreme cases, the cloverleaf skull deformity may prevent the brain from growing to its usual size, causing a build-up of pressure within the skull, known as hydrocephalus. Manifestations of type three are similar to type two but without the cloverleaf skull.
How is Pfeiffer syndrome diagnosed?
Diagnosis of Pfeiffer syndrome often occurs at birth based on the characteristic shape of the skull and skeletal defects involving the hands and feet. Additional tests, such as x-rays, a CT scan, or MRI, may be conducted to assess the skull's shape further and plan appropriate treatment. In cases where the diagnosis is uncertain, molecular genetic testing for FGFR1 and FGFR2 may be conducted to confirm the diagnosis.
How is Pfeiffer syndrome treated?
Treatment of Pfeiffer syndrome is usually conducted in craniofacial centers specializing in treating children with craniofacial conditions. Treatment focuses on correcting the early fusion of the skull, which can be achieved by a series of surgical procedures, usually within the first few months of life. Since bone grows during childhood and adolescence, further surgeries may be needed to correct skull and facial deformities. 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 fluid to drain out and reduce the intracranial pressure. In addition, reconstructive surgery may be performed to help correct skeletal defects involving other body parts, like the hands and feet. Finally, specialized hearing aids may be used to improve hearing loss.
What are the essential facts to know about Pfeiffer syndrome?
Pfeiffer syndrome is a rare genetic disorder characterized by complex craniosynostosis, broad thumbs and big toes, and skeletal defects affecting the hands and feet. A mutation typically causes it in the FGFR1 and FGFR2 genes, which affect how specific cells in the body grow, divide, and die. Diagnosis of Pfeiffer syndrome is based on the characteristic clinical manifestations and can be confirmed by genetic testing. Treatment options include a series of reconstructive skull surgeries, which are typically performed at specialized craniofacial centers.
Watch related videos:
Related linksBones of the skull
Anatomy clinical correlates: Skull, face, and scalp
Resources for research and reference
Rai, R., Iwanaga, J., Dupont, G., Oskouian, R. J., Loukas, M., Oakes, W. J., & Tubbs, R. S. (2019). Pfeiffer type 2 syndrome: review with updates on its genetics and molecular biology. Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery, 35(9), 1451–1455. https://doi.org/10.1007/s00381-019-04244-7
Torres-Canchala L, Castaño D, Silva N, Gómez AM, Victoria A, Pachajoa H. (2020). Prenatal Diagnosis of Pfeiffer Syndrome Patient with FGFR2 C.940-1G>C Variant: A Case Report. Appl Clin Genet;13:147-150 https://doi.org/10.2147/TACG.S251581Vogels, A., & Fryns, J. P. (2006). Pfeiffer syndrome. Orphanet Journal of Rare Diseases, 1, 19. https://doi.org/10.1186/1750-1172-1-19