An Overview of Pfeiffer Syndrome

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Pfeiffer syndrome is a rare genetic condition that causes premature fusion of the bones of the skull of a baby while in its mother's womb. The early fusion causes deformities of the head and face. 

There are three subtypes of Pfeiffer syndrome and all affect appearance, but types 2 and 3 cause more problems, including brain and nervous system issues and developmental delays. Treatment usually starts after the child is born and depends on the child’s symptoms and the severity of the condition.

According to the Genetics Home Reference page for the National Institutes of Health, Pfeiffer syndrome affects one out of every 100,000 people.

Causes

Pfeiffer syndrome is caused by a genetic mutation in the fibroblast growth factor receptor (FGFR) genes. These genes control growth and cell maturing in the human body. Pfeiffer syndrome is either caused by FGFR-1 or FGFR-2. Type 1 is associated with the FGFR-1 gene mutation while the FGFR-2 mutation causes types 2 and 3.

The majority of babies with this condition develop it as a result of a new mutation. But a parent with Pfeiffer syndrome can pass the condition on to their children. There is a 50 percent chance of passing the genetic mutation on, according to the National Craniofacial Association. 

Research reported in the American Journal of Human Genetics suggests that sperm from older men has a higher chance of mutating. In these instances, types 2 and 3 are more common. 

How Genetic Disorders Are Inherited

Symptoms

Presence and severity of symptoms in Pfeiffer syndrome are based on the three subtypes:

Type 1

Type 1 is often called “classic” Pfeiffer syndrome. It is a milder disease in comparison to types 2 and 3. Infants born with type 1 will have premature fusion of the skull bones, called craniosynostosis. A child with type 1 may also have a high forehead, underdeveloped mid-face, widely spaced eyes, an underdeveloped upper jaw, and crowded teeth.

People born with type 1 will have normal intellect. Further, their prognosis with treatment is generally good and life expectancy is not affected.

Type 2

Infants born with type 2 will have more severe craniosynostosis. In type 2, the skull will have a cloverleaf skull deformity, where the skull has a tri-lobed appearance. This is likely due to fluid accumulation in the brain, called hydrocephalus. Facial features of type 2 may include a high broad forehead, severe eye protrusion, flatted mid-face, and a beak shaped nose. There may also be breathing problems related to windpipe, mouth, or nose deformities.

Type 2 may cause hand and foot deformities and limb malformation affecting mobility, and there might be problems with internal organs. Infants born with type 2 are more likely to have intellectual disabilities and neurological problems. Many symptoms of type 2 can be life-threatening if not managed appropriately.

Type 3

Pfeiffer syndrome type 3 is similar to type 2, but infants with this condition do not have the cloverleaf skull deformity. Type 3 causes a shortened skull base, natal teeth (teeth present at birth), severe eye protrusion, and various issues with internal organs. Type 3 causes intellectual disability and severe neurological issues. The outlook for infants born with type 3 is often poor and there is a higher chance of early death.  

Diagnosis

A diagnosis of Pfeiffer syndrome can be made while the fetus is still in the womb using ultrasound technology. A doctor will look to see whether the skull, fingers, and toes are developing normally. 

After the child is born, a diagnosis can easily be made if symptoms are visable. However, if symptoms are mild, they might be missed until the child is a few months or years old and bone growth and development is more evident. 

Imaging studies and physical examination can confirm premature bone fusions in the skull and any limb, finger, and toe deformities. Genetic testing can rule out other conditions and confirm gene mutations.

Accuracy of Ultrasounds in Diagnosing Birth Defects

Treatment

There is no cure for Pfeiffer syndrome. Treatment will depend on the child’s symptoms. Surgery is the main treatment and may include one or more of the following:

  • Skull surgery: The initial surgery to reshape the child’s head is done as early as three months and by 18 months of age. Two or more skull surgeries may be needed to correct skull deformities.
  • Midface surgery: Some children will need to have jaw and midface bones corrected. These surgeries are usually done when the child is a few years old.
  • Dental work: Dental surgery can correct underbites and fix teeth that are out of place.
  • Surgery for extremities: Surgery can correct deformities of the fingers, toes, and limbs.
  • Treatment of breathing issues: Some children may need midface surgeries to remove blockages. Others may need tonsils or adenoids (tissues in the back of nose) removed. A tracheostomy can correct windpipe problems.

Other treatments for Pfeiffer syndrome include:

  • CPAP mask to manage sleep apnea due to facial blockages
  • Speech and language therapy
  • Physical and occupational therapy
  • Medications to treat seizures

Complications

Serious complications of Pfeiffer syndrome include respiratory problems and hydrocephalus. Breathing problems are generally related to trachea abnormalities or blockages in the midface. Hydrocephalus can lead to mental impairment if not treated. Further, facial deformities may cause severe displacement of the eyes and make it hard to close the eyelids. Children with type 2 and 3 may have seizures.

Complications can cause early death depending on seriousness. Death in infancy might be the result of severe brain problems, breathing issues, premature birth, and surgical complications.

A Word From Verywell

Children both with Pfeiffer syndrome types 2 and 3 will need multiple surgeries for reconstruction of the skull, hands and feet, and other joints, and treatment for affected organs. Children with type 1 are treated with early surgery and for physical and occupational therapies. The outlook for type 1 is much better than for types 2 and 3. This is because types 2 and 3 may affect the brain, breathing, and ability to move.

Surgeries may not completely offer a normal appearance for people with Pfeiffer, but they can offer significant improvement. Early treatment and long-term physical and occupational therapy can help most children with Pfeiffer syndrome well into adulthood with only some complications and difficulties. Further, many children with this condition are able to play with their peers and go to school. 

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