Pfeiffer Syndrome

What is Pfeiffer syndrome?

Pfeiffer syndrome is a genetic condition that causes abnormal bone fusion. In most cases, this involves the plates of the skull fusing prematurely, which can cause distinctive facial features such as wideset, bulging eyes or a high forehead. It can also cause problems with bone growth in the hands and feet, leading to shortened digits, thumbs, and big toes that bend away from the other fingers and toes. There are three types of Pfeiffer syndrome:

• Type 1 contends mainly with physical symptoms, and patients can go on to have a normal intelligence and lifespan
• Those with Types 2 and 3 typically suffer from neurological problems, impaired brain development, breathing problems, and a shortened lifespan.

Pfeiffer syndrome is very rare. For all types of Pfeiffer syndrome, it’s estimated that only one in 100,000 people are affected.

What causes Pfeiffer syndrome?

Pfeiffer syndrome is caused by a mutation in the FGFR2 or FGFR1 genes. These genes send instructions to make proteins called fibroblast growth factor receptors, which are responsible for triggering bone cell growth in an embryo. Mutated FGFR genes spend too long “signaling” the production of bone cells, which leads to premature skull fusion and other problems with bone growth. To make a diagnosis, doctors will make a number of clinical observations of the skull, face, hands, and feet to look for the features characteristic of Pfeiffer syndrome. If clinical observation alone leaves room for doubt, molecular genetic testing may be conducted to confirm the diagnosis.

What are the symptoms of Pfeiffer syndrome?

Type 1 Pfeiffer syndrome symptoms are generally visible in infancy and can include:

• Craniosynostosis (premature fusion of bones in skull that affects the shape of the skull)
• High and/or full forehead
• Ocular hypertelorism (widely spaced eyes)
• Midface hypoplasia (underdeveloped midfacial region)
• Hypoplastic maxilla (underdeveloped upper jaw)
• Dental problems

Additionally, infants with Type 2 and 3 Pfeiffer syndrome can have symptoms that are more pronounced and severe:

• A “cloverleaf” shaped skull that indicates a more severe form of craniosynostosis (Type 2 only)
• Hydrocephalus (a serious condition caused by the accumulation of cerebrospinal fluid (CSF) in the skull, which puts pressure on the brain)
• A “beaked” nose
• Ocular proptosis (severe eye protrusion)
• Ankylosis (lack of joint mobility in the elbows)
• Impaired mental development
• Neurological problems
• Shortened base of the skull (Type 3 only)
• Abnormal teeth at birth (Type 3 only)

How do people inherit Pfeiffer syndrome?

Pfeiffer syndrome is an autosomal dominant pattern genetic disorder, so only one copy of an abnormal gene from either parent is needed to pass on the disorder. This means an affected parent has a 50/50 chance of passing on the gene with each pregnancy. However, the disorder can also be the result of a completely new mutation, and nearly every Type 2 or 3 case is the result of a new mutation.

What treatments are available for Pfeiffer syndrome?

Pfeiffer syndrome treatment focuses on easing individual symptoms. For those patients whose skull deformities have created pressure on the brain (hydrocephalus), doctors may perform corrective surgery or insert a special tube called a shunt to drain excess cerebrospinal fluid out of the skull to another part of the body. In some cases, reconstructive surgery may be appropriate to correct some facial abnormalities or address breathing and hearing difficulties. Surgery, physical therapy, and orthopedic support may help improve mobility. Parents need to work with their pediatric team and a range of surgeons and specialists to determine which measures are safe and suitable for their children.

Where can I find more information about Pfeiffer syndrome?

• U.S. National Library of Medicine
• National Organization for Rare Disorders (NORD)