Genetics Northern California

Pfeiffer Syndrome

Pfeiffer syndrome is a rare genetic disease characterized by craniosynostosis (premature fusion of the cranial sutures), mild syndactyly (webbing) of the hands and feet, and abnormal facial features. It has also been called acrocephalosyndactyly V and Noack syndrome. The craniosynostosis associated with Pfeiffer Syndrome is highly variable and results in an abnormal skull shape. Most patients will appear to have somewhat of a cone-shaped head. The syndactyly of the fingers and toes usually occurs between the second and third digits. The thumbs and great toes are short, broad, and often malformed; they may bend outward. A typical Pfeiffer’s patient has a flatter appearance to the face, ears that are slightly lower-set than usual, more prominent eyes, a depressed nasal bridge, and a high-arched palate.

There are three subtypes according to severity: Pfeiffer syndrome Types I, II, and III, with Types II and III being more common. With all three subtypes combined, the incidence of Pfeiffer syndrome is about 1 in 100,000 newborns. 

Pfeiffer syndrome is a genetic disorder caused by a change (mutation) in a gene. At least two different genes can cause the same clinical findings of Pfeiffer syndrome. The two genes known to cause Pfeiffer syndrome are fibroblast growth factor receptors 1 and 2 (FGFR1 and FGFR2). If the cause is familial (one or both parents have the condition), the disease is inherited in an autosomal dominant fashion.  Pfeiffer syndrome can sometimes happen for the first time in a family because of a new genetic change, also called a "de novo mutation". This random change happens when the sperm or egg cell is being formed. In these families, neither parent is affected.

The diagnosis of Pfeiffer syndrome is made based on the clinical findings described in the definition above.

As mentioned, the craniosynostosis should be of primary concern for treatment of young children with Pfeiffer syndrome. Various surgeries are available, most of which remove and replace part of the skull bone to relieve pressure on the brain. Due to problems with breathing and eating, many affected children require a tracheotomy and a gastrostomy tube. Surgical repair of the syndactyly of the fingers and toes, as well as cosmetic reconstruction of the facial dysmorphisms, are surgical procedures to be considered once the child is older.

Children with Pfeiffer syndrome require a long-term surgical plan and pro-active treatment. The coordinated efforts of a specialized team can help a child with Pfeiffer Syndrome reach adolescence with a minimal number of syndrome-related problems.

Speech articulation disorders are seen secondary to Class III dental malocclusion. All anterior sounds are distorted or substitutions made. Hoarse voice is common, related to tracheal problems. Hyponasal resonance is also common due to choanal stenosis and/or a small nasopharynx. Midface advancement surgery may positively affect articulation and resonance.

Conductive hearing loss is common, often reaching to the moderate to severe range. Medical management with consideration for hearing aids is recommended.

Perhaps the most important concern for children with Pfeiffer syndrome is the inhibited growth of the brain that results from craniosynostosis. If the fused sutures are not surgically corrected, the child’s brain will develop in abnormal directions. Beyond this, the expressivity of this syndrome is highly variable. Many affected children have difficulties breathing and eating due to the recessed midface. As a result of the shallow orbits associated with the syndrome, some children do not get adequate protection of their eyes and the low set ears may cause mild hearing loss. Complications such as seizures have been reported in a minority of cases. The majority of children have normal intelligence.


Genetics Home Reference: Pfeiffer syndrome - General information about Pfeiffer syndrome provided as a service of the National Library of Health. Also includes links to related sites.