Pfeiffer syndrome

What is Pfeiffer syndrome?

Pfeiffer syndrome is an inherited disorder that affects how the bones in the head, feet and hands develop. It is characterized by craniosynostosis, a birth defect resulting from the premature fusion of the skull bones. This early fusing of the bones prevents the skull from developing normally.

Abnormal skull development affects the shape of the head, face and eyes. With Pfeiffer syndrome, the skull tends to be short and elongated, causing the head to take on an irregular shape. Early closing of the skull bones can increase pressure within the brain. This may impact brain development and lead to other health concerns.

Protruding eyes and enlarged thumbs and toes are common characteristics of the condition.

Pfeiffer syndrome was first described by German geneticist Rudolf Pfeiffer in 1964. A rare disorder, Pfeiffer syndrome affects one in 100,000 live births. It is estimated that fewer than 50,000 people in the United States have the condition.

Causes and genetics

The cause of Pfeiffer syndrome is rooted in genetics. It is an autosomal dominant disorder that causes mutations in fibroblast growth factor receptor (FGFR) genes. “Autosomal” means the condition is just as common in men and women. “Dominant” means an abnormal gene only needs to be passed down from one parent to be inherited. FGFRs are involved in human development before and after birth.

Pfeiffer syndrome results from a mutation in FGFR1 or FGFR2. It is most commonly a result of FGFR2 mutations.

Pfeiffer syndrome may be inherited from either parent carrying the mutated gene. There is a 50% risk of an affected parent passing the mutated gene to a child. Some individuals may have the mutated gene yet show no signs or symptoms of the condition.

The abnormal gene may also be the result of a new mutation in a child. Advanced paternal age has been linked to an increased risk of Pfeiffer syndrome in new mutations.

Symptoms and diagnosis

Pfeiffer syndrome can cause a range of signs and symptoms in affected individuals. Symptoms may be detected during pregnancy through prenatal imaging. Symptoms may also be noticeable within the first four weeks of life.

Pfeiffer syndrome symptoms can vary in extent and severity. Some of the more common signs and symptoms include:

• Cloverleaf skull

• Short, broad thumbs and big toes

• Curved fingers (generally the pinky)

• Webbing between fingers and toes

• High forehead

• Underdeveloped cheekbones

• Broad nasal bridge

• Facial asymmetry

• Dental abnormalities

Pfeiffer syndrome may also affect an individual’s eyes and vision. Such signs and symptoms may involve:

• Widely spaced eyes (hypertelorism)

• Bulging eyes (exophthalmos)

• Droopy eyelids (ptosis)

• Refractive errors

• Lazy eye (amblyopia)

• Crossed eyes (strabismus)

• Shrinking of the optic nerve (optic atrophy)

• Swelling of the optic discs

• Keyhole appearance to the pupil (iris colobomas)

• Drying out of the cornea (exposure keratopathy)

Most people affected by Pfeiffer syndrome have conductive hearing loss. Severe cases may cause visual impairment. Respiratory and neurological issues may also occur.

Diagnosis

Pfeiffer syndrome is diagnosed according to the physical manifestations of the condition.

Prenatal ultrasounds may allow physicians to identify physical characteristics before birth. However, a diagnosis can be difficult to confirm at this stage.

Genetic testing may be conducted to determine whether a mutation of the FGFR1 or FGFR2 gene exists. The only method of preventing the disorder is genetic counseling.

Types of Pfeiffer syndrome

Three types of Pfeiffer syndrome have been identified and described. Types II and III are the most serious. Pfeiffer syndrome type I is associated with mutations of FGFR1 and FGFR2. Types II and III are related to mutations of FDFR2.

Pfeiffer syndrome type I

Type I is the most common form of Pfeiffer syndrome, which generally produces milder symptoms. It is often characterized by:

• A short and tall appearance of the head

• Widely spaced eyes

• An underdeveloped mid-facial area

• A tall forehead

• Dental abnormalities

• A prominent lower jaw

• An underdeveloped upper jaw

Individuals with Pfeiffer syndrome type I tend to be of normal intelligence.

Pfeiffer syndrome type II

The effects of Pfeiffer syndrome type II typically are more severe than type I. Common characteristics include:

• Cloverleaf skull (a trilobular appearance to the head)

• Hydrocephalus (extra fluid in the brain that causes increased pressure)

• Elbow stiffness due to joint fusion

• Malformation of the arms, legs, hands, feet and organs

Individuals with type II often suffer neurological disorders and impaired mental development.

Pfeiffer syndrome type III

Pfeiffer syndrome type III produces effects similar to type II. However, Cloverleaf skull is not a characteristic of this form. The base of the skull may be shorter than normal, and the eyes may protrude severely. Organs may be underdeveloped, and teeth may be present at birth.

Individuals with type III may have severe neurological issues and impaired mental development.

Treatment and management

Treating Pfeiffer syndrome and its effects typically involves a team of medical specialists. This may include pediatricians, neurologists and orthopedists. Ear, nose and throat specialists, eye specialists and other providers may also be involved.

Treatment generally centers on reducing the individual symptoms of the condition. It is often case-specific and personalized to support each patient’s needs.

Surgery may be necessary to address various functional and cosmetic concerns. Surgery to relieve pressure in the brain or improve airway passages may also be advised. Further surgical options may be considered to treat abnormalities of the head, face, ears, limbs and other areas of the body. In many cases, a surgical treatment plan occurs in several stages and may begin within the first year of life.

To avoid drying out of the surface of the eye, surgically moving the bones around the eye and the forehead forward can help.

Other types of Pfeiffer syndrome treatment involve supportive therapies. These may include:

• Special hearing aids

• Physical therapy

• Social support

• Special education

• Speech therapy

• Occupational therapy

• Treatment of visual impairment

Genetic counseling is advised for families affected by Pfeiffer syndrome. Clinical trials and research studies may also be available. Additional information on clinical studies can be found at clinicaltrials.gov.

Prognosis

The prognosis for Pfeiffer syndrome varies according to the type and severity of the condition. Pfeiffer syndrome type I has a good prognosis for normal cognitive development. It also carries a normal life expectancy when treatment is received within the first year of life.

Infants with type II and type III may develop life-threatening health problems without proper care and treatment. The prognosis for Pfeiffer syndrome types II and III is less favorable. However, it may improve with early treatment and intervention.

The appearance of the head and face often improves as the patient ages.

People living with Pfeiffer syndrome generally need ongoing care and support from a multidisciplinary healthcare team.

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Page published on Wednesday, June 28, 2023

Page updated on Wednesday, July 5, 2023

Medically reviewed on Tuesday, June 6, 2023