First described in 1946, Pfeiffer syndrome is a condition categorized under an umbrella grouping of craniofacial and limb disorders called craniosynostosis. Pfeiffer syndrome afflicts a reported and estimated number of 1 in every 100,000 children. In babies born without one of these genetic craniofacial syndromes, the different ‘plates’ of the skull are not fused during gestation and over a developmental period of time, agglutinate together to form the adult skull. Simply put, craniosynostosis varies in severity as well as characteristically, but in general, causes health issues that require very specialized treatment and care for affected children.
What is Pfeiffer Syndrome?
Pfeiffer syndrome is a rare genetic disorder characterized by the premature fusion of skull bones (craniosynostosis), which prevents further growth of the skull and leads to bulging wide-set eyes (ocular proptosis), a high prominent forehead (turribrachycephaly), an underdeveloped upper jaw (maxillary hypoplasia), and a beaked nose. Over half of all children with Pfeiffer syndrome also have hearing loss, and dental problems are frequent as well. Common limb abnormalities due to Pfeiffer syndrome include thumbs and first (big) toes that are wide and bend away from the other digits, short fingers and toes (brachydactyly), and webbing or fusion between the digits (syndactyly).
There are three subtypes of Pfeiffer syndrome: type 1, type 2, and type 3. Type 1 is known as classic Pfeiffer syndrome and has been symptomatically described above. Typically, people with type 1 Pfeiffer syndrome are of normal intellectual capacity and lifespan. Type 2 and type 3 are more acute forms of Pfeiffer syndrome and are typically associated with problems with the nervous system. With type 2 and 3, the particular early fusion of the skull bones can cause slow development and other neurological abnormalities. Type 2 is differentiated from type 3 by the appearance of a clover-shaped head, which stems from more substantial or comprehensive premature fusion of the skull bones.
What Causes Pfeiffer Syndrome?
Pfeiffer syndrome is not a product of something the mother did or did not do during pregnancy. Physicians believe Pfeiffer syndrome is purely the result of a gene alternation, which occurs due to currently unknown reasons. Receiving just one copy of the altered gene in each cell is enough for a person to inherit Pfeiffer syndrome from a parent or, more rarely, spontaneously develop the mutation.
Pfeiffer Syndrome and Genetics
Specifically, Pfeiffer syndrome is genetically believed to be the result of altered FGFR1 and FGFR2 genes, which are mapped to chromosomes 8 and 10. These genes are culpable for making proteins called fibroblast growth receptors 1 and 2. These proteins have several functions, one of which is being the signal for immature cells maturing into bone cells during fetal development. An alteration in either the FGFR1 or FGFR2 gene changes the protein function and produces an extended period of signaling, which leads to the early fusion of skull bones, as well as abnormal development of bones in the feet and hands. To distinguish, type 1 Pfeiffer syndrome is caused by mutations in either the FGFR1 or FGFR2 genes, while type 2 and 3 Pfeiffer Syndrome are only caused by a mutation of the FGFR2 gene. Type 2 and type 3 have not been related at this point to any change of the FGFR1 gene.
A person with Pfeiffer syndrome has a 50% risk of passing on the condition to his or her own children. If both parents are unaffected, there is still a very small chance that a genetic mutation may still occur during gestation to produce a child with Pfeiffer syndrome.
Problems Associated with Pfeiffer Syndrome
Children with Pfeiffer syndrome may experience the following associated problems in varying degrees:
- Poor vision
- Obstructive sleep apnea (OSA)
- Dental issues caused by crowded teeth and usually a high palate
- Hearing loss (in nearly 50% of children)
Treatment for Pfeiffer Syndrome
Treatment for Pfeiffer syndrome is complicated and typically intended to ameliorate the skull and mid-face abnormalities, as well as the problem of obstructive sleep apnea that often accompanies Pfeiffer syndrome. Depending on the severity of the characteristics associated with Pfeiffer syndrome, children with this condition may need some or all of the following treatments and surgical procedures:
- Skull surgery—Most children will require 2-4 skull surgeries over the course of their lifetime including a frontal orbital procedure. The first skull surgery is usually performed at some point during the first 18 months of a baby’s life.
- Mid-face surgery—The most recurrent procedure performed to shift the bones of the mid-face forward is called the LeFort III operation. This is typically performed between 6-8 years of age. This surgery is implemented to both achieve a more normal facial appearance and treat obstructive sleep apnea.
- Obstructive sleep apnea monitoring/treatment—A child with Pfeiffer syndrome should be monitored for obstructive sleep apnea by a craniofacial team, due to the underdevelopment of the mid-face. In slight cases, medications may be sufficient to treat obstructive sleep apnea, but for more severe cases, a tonsillectomy and/or continuous positive airway pressure (CPAP) treatment may be necessary. In infants with Pfeiffer syndrome, a tracheostomy procedure may also be required to ensure the baby can properly breathe.
- Orthodontic treatment-Orthodontic treatment for Pfeiffer syndrome may include dental braces to alleviate severe crowding of teeth as well as jaw surgery to correctly line up the lower face.