What Is Pfeiffer Syndrome?

Pfeiffer syndrome is a rare genetic condition that causes the bones of the skull to join together (fuse) while a fetus is still in the womb. It also goes by the name acrocephalosyndactyly type V.

The early fusion of the bones seen with Pfeiffer syndrome means a baby is born with deformities of the head and face. This prevents normal growth of the skull. In addition, some also experience hand and foot deformities.

These are three types, with Pfeiffer syndrome types 2 and 3 being the most severe. These can cause significant developmental issues and a shortened life. Pfeiffer syndrome type 1, considered a milder form, is the most common and does not impact one's lifespan.

Types and Features of Pfeiffer Syndrome

The three types of Pfeiffer syndrome vary in terms of their signs and impact they can have on a child.

Pfeiffer Syndrome Type 1

Type 1 is often called “classic” Pfeiffer syndrome. It is a milder form of the condition than types 2 and 3.

In type 1 Pfeiffer syndrome, babies are born with early-fused skull bones (craniosynostosis). This can change their appearance.

For example, a child with type 1 Pfeiffer syndrome may have a:

• High forehead
• Underdeveloped mid-face
• Widely spaced eyes
• Underdeveloped upper jaw
• Crowded teeth

People born with type 1 will have normal intellectual development.

If the condition is diagnosed and treated, their life expectancy is not affected and they may not have any major health problems.

Pfeiffer Syndrome Type 2

Infants with type 2 Pfeiffer syndrome have more severe craniosynostosis. The skull will have what is called a cloverleaf skull deformity where the skull has a tri-lobed appearance (like a clover).

The appearance is thought to be related to fluid build-up in the brain (hydrocephalus). 

The facial features of a child with type 2 Pfeiffer syndrome may include a:

• High broad forehead
• Severe eye protrusion
• Flatted mid-face
• Beak-shaped nose

A child may have breathing problems related to windpipe, mouth, or nose deformities.

Type 2 may also cause hand and foot deformities. Limb malformation can affect a child's mobility, and there might be problems with their internal organs. 

Infants born with type 2 are more likely to have intellectual disabilities and neurological problems.

If it's not diagnosed and treated early, Pfeiffer syndrome type 2 can be life-threatening.

Pfeiffer Syndrome Type 3

Pfeiffer syndrome type 3 is similar to type 2, but infants do not have the cloverleaf skull deformity. 

A child with type 3 Pfeiffer syndrome may have a:

• Shortened skull base
• Teeth present at birth (natal teeth)
• Severe eye protrusion
• Problems with their internal organs

Type 3 causes intellectual disability and severe neurological problems.

There is a chance that babies born with type 3 Pfeiffer syndrome will die.

What Causes Pfeiffer Syndrome?

Pfeiffer syndrome is caused by a genetic mutation in a gene called fibroblast growth factor receptor (FGFR). These genes control cell growth and cell maturing.

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.

Most babies with Pfeiffer syndrome get it because a new mutation pops up rather than because they have inherited the gene from a parent. However, a parent with Pfeiffer syndrome can pass the condition on to their children.

According to the National Craniofacial Association, there is a 50% chance of a parent passing the genetic mutation on to their child.

Research has also shown that sperm from older men has a higher chance of mutating and may contribute to the risk of Pfeiffer syndrome types 2 and 3.

Pfeiffer syndrome affects one out of every 100,000 people. The name may sound familiar as it was revealed that the late son of the late singer Prince had Pfeiffer syndrome type 2.

Complications of Pfeiffer Syndrome

The deformities of the head and face in Pfeiffer syndrome can lead to respiratory problems and swelling of the brain (hydrocephalus).

Complications of Pfeiffer syndrome can include:

• Breathing problems, usually caused by trachea abnormalities or blockages in the face
• Severe displacement of the eyes that make it hard to close the eyelids and/or impact vision
• Hydrocephalus that can lead to brain damage if it's not treated
• Seizures (type 2 and type 3 Pfeiffer syndrome only)

Can Pfeiffer Syndrome Be Diagnosed Before Birth?

Pfeiffer syndrome can be diagnosed before birth. While the fetus is still in the womb, a provider will use an ultrasound to check if the fetus's skull, fingers, and toes are developing normally.

If it's not seen before birth, a diagnosis of Pfeiffer syndrome can easily be made if symptoms are visible when a baby is born. However, if symptoms are mild, they might be missed until the child is a few months or years old, when bone growth and development are 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 linked to Pfeiffer syndrome.

Pfeiffer Syndrome Treatment

There is no cure for Pfeiffer syndrome, but it can often be treated. The treatment for Pfeiffer syndrome depends on the type and the symptoms it's causing.

The main treatment for Pfeiffer syndrome is surgery. A child with Pfeiffer syndrome might need one or more of the following surgeries:

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

There are also some non-surgical treatments for Pfeiffer syndrome, including:

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

Life Expectancy and Other Outcomes

Babies born with Pfeiffer syndrome may die from the condition. Death can be caused by severe brain damage, breathing problems, premature birth, and surgical complications.

For babies who survive infancy, their outcomes will depend on the type of Pfeiffer syndrome they have:

• A child with type 1 Pfeiffer syndrome is treated with early surgery. They will also need physical and occupational therapies. 
• A child with Pfeiffer syndrome type 2 or 3 will need to have multiple surgeries to fix their skull, hands and feet; and other joints. They will also need specific treatments for the organs that are affected by the condition.

The outlook for children with type 1 Pfeiffer syndrome is much better than for types 2 and 3 because types 2 and 3 can affect the brain, breathing, and a child's ability to move.

Surgeries may not give a child with Pfeiffer syndrome a "normal" appearance, but they can address some of the complications from the physical differences.

Early treatment and long-term physical and occupational therapy help most children with Pfeiffer syndrome. Many children are able to play with their peers and go to school, and they often live into adulthood with only some difficulties related to the condition.

Summary

Pfeiffer syndrome is a rare genetic condition. It causes the bones of the skull to fuse too early while a fetus is still developing in the womb. Babies with Pfeiffer syndrome are born with deformities in their heads and faces, which can lead to problems breathing and brain swelling.

Sometimes, babies die from Pfeiffer syndrome's effects or complications from surgeries to try to fix them. When children with Pfeiffer syndrome grow up, they may have health concerns related to the condition, depending on the type they have.

When the condition is not severe, it's diagnosed early, and treatment and support are available, a child with Pfeiffer syndrome can participate in many typical activities, like going to school.