Like Crouzon and Apert syndromes, Pfeiffer syndrome is caused by inheriting a gene. Pfeiffer syndrome follows autosomal dominant inheritance pattern, which means that roughly half of the children of a patient with Pfeiffer syndrome can be expected to inherit the syndrome. Like Crouzon and Apert syndromes, in most cases it is caused by a mutation in the gene for fibroblast growth factor receptor 2 (FGFR-2). In about 5% of cases, Pfeiffer syndrome is caused by a mutation in the FGFR-1 gene, causing these patients to have a milder appearance that looks more like that of children with Crouzon syndrome. Overall Pfeiffer syndrome occurs in about one in 100,000 births. There can be considerable variation in the appearance and severity of problems in these patients. For this reason we organize patients with Pfeiffer syndrome into one of three subtypes to care for them more efficiently. The signs for Pfeiffer syndrome common in all types include:
Patients with type I Pfeiffer syndrome usually have normal intelligence. Typically craniosynostosis of both of the coronal sutures is present causing similar head shape to Apert syndrome. The skull is vertically tall and wide with the appearance of towering or leaning forward (turricephalic). The skull is very flat in the back and is short from front to back.
Patients with types II and III tend to have more severe medical problems and are more likely to have learning delays. Type II patients have a unique “cloverleaf” skull shape. Type III patients generally have the most severe problems, but do not have a cloverleaf skull shape.
In general, all of these patients have eyes that look larger than normal. This is caused by a normal-sized eye sitting in a very shallow eye socket (orbit). The orbits are shallow because both the forehead and middle portion of the face are not able to grow forward like they should. Sometimes this makes it difficult for the eyelids to close fully, and patients can have problems with dry eyes. If this problem is severe, a surgery can help the eyelids close to protect vision. The orbits are also rotated outward and farther apart from one another, giving an abnormal downward tilt and wide spacing to the eyes.
The middle part of the face is vertically short and flat, coming from an undeveloped upper jaw. The palate is also highly arched. Often, the middle part of the face is placed so far back that these patients may not be able to breathe safely. These patients frequently need a tracheostomy to help them breathe safely. This problem is most common with type II and III patients; The upper and lower teeth are usually not lined up, which needs corrective surgery when the child is fully grown.
The thumbs and big toes of these patients are very large. This is a unique feature of Pfeiffer syndrome and can help diagnosis before genetic testing is complete. Occasionally, these patients will have a webbing of fingers (syndactyly), which can be fixed by an experienced hand surgeon.
Patients with Crouzon syndrome are at a high risk for hydrocephalus. This is a build up of the cerebrospinal fluid (CSF) that the brain is surrounded by. This can cause very high pressure in the skull that requires drainage or the CSF using a shunt to protect the health of the brain. These patients are also at a high risk for developing Chiari malformation. This affects the back part of the brain (cerebellum), which is important for balance and coordination. A Chiari malformation is when part of the cerebellum pushes into the opening in the base of the skull where the spinal cord meets the brain (foramen magnum). This can cause a back-up of CSF and increase the blood pressure in the veins draining blood from the brain. Both of these can create high pressure that can harm the brain. This elevated pressure can also affect the brain stem, causing problems with breathing and swallowing.
These patients usually need two to three surgeries to achieve a normal head shape and treat or prevent increased pressure in the skull. They typically need an operation to bring the middle portion of the face forward. They also commonly require a surgery to align the upper and lower jaws when they are fully grown.