Pfeiffer Syndrome

Overview

Pfeiffer Syndrome is a rare genetic disorder that changes how the skull forms in a baby. In Pfeiffer Syndrome the skull bones grow but come together earlier than expected when a baby is developing in pregnancy. This can cause a misshaped skull, which often requires surgery. People with Pfeiffer Syndrome also have differences in the bones of their hands and feet, like shorter fingers, broad thumbs and broad big toes. Since Pfeiffer Syndrome affects babies when they are growing and developing, individuals are born with Pfeiffer Syndrome, and are usually diagnosed at birth.

Symptoms

Many of the characteristics of Pfeiffer Syndrome are due to the early joining of the skull bones. As the brain grows, the skull usually grows with it until age 2. In Pfeiffer Syndrome, the skull has already fused and the growing brain can push on the skull, which leads to a longer skull.

This can affect the face, the spacing of the eyes, the teeth and how the ears form. The symptoms associated with Pfeiffer Syndrome are on a range of severity, and individuals with Pfeiffer Syndrome can have any combination of the listed symptoms.

Example of a child with a misshaped skull

Common traits of individuals with Pfeiffer Syndrome:

Craniofacial: affecting the skull and face

• Misshaped skull: flat forehead and a tall skull
• Sunken face
• Bulging eyes
• Hypertelorism: eyes that sit wider on the face
• Vision problems
• Dental issues: crooked or crowded teeth
• Hearing loss

Neurological: affecting brain function

• Intelligence varies from normal to severe intellectual disability
• Seizures

Respiratory: affecting breathing

• Airway blockage in nose
• Airway blockage in windpipe
• Airway blockage by the tongue
  

  Example of fused toes

Skeletal: affecting the skeleton

• Short fingers and/or toes
• Fused or webbed fingers and/or toes
• Broad thumbs and broad big toes
• Stiff elbows and knees

Symptoms that are bolded and italicized are the most common symptoms seen in individuals with Pfeiffer Syndrome.

Genetics

Our bodies are made of billions of cells. In each of our cells, we have a recipe book that tells our cells what to make for every part of our body. This recipe book is made up of genes, which tell the body to make proteins, that help the body grow and develop when it is supposed to. Proteins are the building blocks to the different tissues and organs that make up our bodies. Genes can also tell cells when to become different tissues, because we need certain tissues at different times during our lifespan. We inherit our genes from our parents, half of them from your mom and the other half from your dad. People get different combinations of their genes to make you, you. Everyone has changes in their genes, which makes all humans unique.

Most of the time, changes in genes don’t have any impact on our bodies. However, sometimes these changes can be in genes that can change the way they function. The differences in an individual with Pfeiffer Syndrome are caused by a change in genes called fibroblast growth factor receptors (FGFR). Only one change in these genes is enough to cause the symptoms of Pfeiffer Syndrome. FGFR1 and FGFR2 are 2 genes that are most commonly seen to have changes in them that cause Pfeiffer Syndrome. They belong to a group of genes that are responsible for making proteins that help to tell cells when to become bones when a baby is developing in their mom. These proteins are important for developing our organs, like our brain and the lungs.

Autosomal Dominant Inheritance

Inheritance

The gene change that causes Pfeiffer Syndrome is inherited in an autosomal dominant pattern. This means that one change in FGFR1 or FGFR2 is enough to cause Pfeiffer Syndrome. A person with Pfeiffer Syndrome has a 50% chance of passing it on to their children.

It can be inherited from your mom or dad, or it can be a new change that was found in the person with Pfeiffer Syndrome. When the gene change is first found in the person who was diagnosed, this is what doctors, researchers and scientists can refer to as de novo. De novo mutations (new mutations) are the most common cause of Pfeiffer Syndrome, meaning that there can be no family history of Pfeiffer Syndrome in your family, and the genetic change happened by chance. Pfeiffer Syndrome affects 1 in 100 000 people, and is found in men and women equally.

Genetic Counselling

A genetic counsellor is a healthcare worker who is trained in genetics and counselling and can help explain genetic conditions like Pfeiffer Syndrome to families. Genetic counsellors can collect medical and family history, and help give the healthcare team more information if Pfeiffer Syndrome is suspected. Genetic counsellors can explain genetic testing options, who can get it, and what the results mean. Genetic counsellors are trained to explain scientific terms in ways so everyone can understand them, so that patients and families can make the best medical decision for themselves.

Diagnosis of Pfeiffer Syndrome

Pfeiffer Syndrome is suspected by the presence of the most common symptoms:

• Skull shape differences
• Short fingers
• Broad thumbs
• Broad big toes

A genetic test can then be completed to see if there is a genetic change in one of the FGFR genes. In Pfeiffer Syndrome, a doctor can order a genetic test that looks at all of the FGFR genes, or just FGFR1 and FGFR2. Genetic counsellors can also be part of the team to help explain what the testing means and what it is looking for.

Types of Pfeiffer Syndrome

An individual with Type 2 Pfeiffer Syndrome, featuring the cloverleaf skull

Type 1 is the most common type of Pfeiffer Syndrome seen in patients. It is sometimes called “classic” Pfeiffer Syndrome. People with Type 1 can have a range of symptoms, but they are often milder compared to Type 2 and Type 3. In Type 1, the symptoms of a misshaped skull, broad thumbs and broad big toes are commonly seen. People with this type of Pfeiffer Syndrome often do not have intellectual disabilities, but this varies.

Type 2 Pfeiffer Syndrome is different from Type 1 since patients have specific skull shape differences. Doctors refer to these differences as a “cloverleaf skull”. Type 2 patients are more likely to have differences in the face (craniofacial symptoms) and skeleton (skeletal symptoms).

Type 3 Pfeiffer Syndrome is similar to Type 2, but individuals do not have the cloverleaf skull.

Differential Diagnoses

There are many other syndromes and conditions that look like Pfeiffer Syndrome, and because it is rare, it can be hard for healthcare providers to detect. Some of these genetic conditions are affected by changes in FGFR1 or FGFR2, or different FGFR proteins. These specific changes can have slightly different impact on people with these changes, and can look different or very similar to Pfeiffer Syndrome.

Some other conditions that Pfeiffer Syndrome can be confused for are:

• Apert Syndrome
• Carpenter Syndrome
• Crouzon Syndrome
• Muenke Syndrome
• Jackson-Weiss Syndrome

These syndromes are named after the researcher or doctor who first wrote about them.

Other Names for Pfeiffer Syndrome include:

• Acrocephalosyndactyly (ACS) Type V
• ACS5
• Noack Syndrome

Management of Pfeiffer Syndrome

Treatment of Pfeiffer Syndrome is based on what symptoms each person has. There is currently no cure for Pfeiffer Syndrome.

Most babies with Pfeiffer Syndrome are suggested to get surgery to reshape their skull. This can help the brain continue growing as individuals get older. The brain sits in cerebrospinal fluid (CSF) in the skull and pressure on the skull can cause the fluid to pool in the brain. This can be helped through surgery to remove the pressure and fluid in the brain and skull. As the brain continues to grow as the child ages, more skull reshaping surgeries may be recommended.

There also may be surgeries that can be done to reshape the ear to help patients with hearing loss, or to get specialized hearing aids.

Since Pfeiffer Syndrome can also impact the way air can get to the lungs, there can be surgeries done to make sure air is able to get to the lungs.

Psychosocial Challenges

Being diagnosed with a rare condition can make you feel alone, with many people not knowing what to expect. Support groups, and reading about other craniofacial conditions may help. See Resources for different associations for further information and to learn more about other people's journeys.

Intelligence of individuals with Pfeiffer Syndrome can vary. People may have normal intelligence, but others may live with an intellectual disability. People with Pfeiffer Syndrome often benefit from educational assistance during school, to help them reach their full potential. Pfeiffer Syndrome can impact the way your face looks, which can be challenging for kids, parents and families. Support groups for craniofacial differences can be a good place to start to find support and build relationships in the community. Online message boards and Facebook group pages exist for Pfeiffer Syndrome

Resources

Pfeiffer Syndrome can impact the way your face looks, which can be challenging for kids, parents and families. Support groups for craniofacial differences can be a good place to start to find support and build relationships in the community.

Children's Craniofacial Association: https://ccakids.org/

My Face: https://www.myface.org/

Faces: National Craniofacial Association: https://www.faces-cranio.org/