Pfeiffer syndrome

All reported cases of Pfeiffer syndrome type 3 are from gene changes that are new to the affected person. This means that parents do not have the gene change to pass on. Parents of a child with Pfeiffer syndrome type 3 are also unlikely to have another affected child.

Nearly all cases of Pfeiffer syndrome type 2 are from gene changes that are new to the affected person. This means that parents do not have the gene change to pass on. Parents of a child with Pfeiffer syndrome type 2 are unlikely to have another affected child.

Pfeiffer syndrome type I is inherited in an autosomal dominant manner, which means that only one of the two versions of a gene has a harmful change. This means that if a person is affected, each of their children will have a 50% chance being affected. If a child is affected, but neither parent is affected, then the chance of having another child with the condition is low.

Pfeiffer syndrome type 3 cannot be cured, but surgery on the bones in the skull helps correct some of the changes to the head. Craniosurgery allows for more growth of the brain by giving it more space. A CT scan can be used to map the bones in the head to plan surgeries. Some affected people require more than one surgery. Sometimes surgery is performed to reduce the bulging eyes and to give the face a more typical appearance.

Pfeiffer syndrome type 2 cannot be cured, but surgery on the bones in the head may help correct some of the changes to the head. This surgery allows for more growth of the brain by giving it more space. A CT scan can be used to map the bones in the head to plan surgeries. Some affected people require more than one surgery. Sometimes another surgery is performed to reduce the bulging eyes and create a more typical looking face.

Pfeiffer syndrome type 1 cannot be cured, but surgery on the bones in the head helps correct some of the changes to the face. A CT scan can be used to map the bones in the head to plan surgeries. Some affected people require more than one surgery.

The FGFR1 and FGFR2 genes give instructions on how to make proteins. These proteins have many functions, one of which is to signal for immature cells to become bone cells. Certain changes to the FGFR1 or FGFR2 genes, cause the protein to signal for longer than usual causing too many immature cells to turn into bone cells before a baby is born. This changes how certain parts of the body form, causing premature fusion of the skull bones, and changes in bones of the elbows, hands, and feet.

One specific change in FGFR1, labeled p.Pro252Arg has been found in five separate families and is associated with a mild form of Pfeiffer syndrome type 1.

Identical changes in the FGFR2 gene have been shown to cause Pfeiffer syndrome in some individuals, while causing Crouzon syndrome or Jackson-Weiss syndrome in other individuals. This suggests that there are other factors which determine an individual’s symptoms. While these were once considered distinct syndromes, they are now described as belonging to the FGFR-related craniosynostosis spectrum.

Because inheritance of Pfeiffer syndrome type 1 is autosomal dominant, it is likely that one parent is affected, possibly mildly. For this reason, testing the parents is recommended to see if one of them carries the same gene change. If the same gene change is found in a parent, then every time that parent has a child, that child has a 50% chance of having the same gene change causing Pfeiffer syndrome type 1. Because of this testing is recommended for children of people with Pfeiffer syndrome type 1. If the gene change is found to be new in the affected child, then brothers and sisters would not need to be tested.

If you are concerned about the risk of having a child with Pfeiffer syndrome and the options available, you may wish to speak to a certified genetic counselor, who can answer your questions and tailor the information to your specific situation. A list of genetic counselors is available on the National Society of Genetic Counselors website as well as on the Canadian Association of Genetic Counsellors website.

Treatment may require the coordinated efforts of a team of specialists. The team may involve pediatricians; plastic surgeons; neurosurgeons; dentists that specialize in straightening crooked teeth (orthodontists); speech pathologists; ear, nose, and throat specialists (otolaryngologists); neurologists; specialists who assess and treat hearing problems (audiologists); physicians who diagnose genetic conditions (geneticists); and genetic counselors who help families understand the details of their genetic diagnosis.

This team of specialist will work closely with you and your child to customize the treatment plan to your child’s specific needs.

The Cleft Palate Foundation has a list of medical centres with teams specializing in craniofacial surgery (surgery of the head and face) as well as teams specializing in cleft palate repair. This list is organized by state for those living in the USA and by country for those living outside of the USA.
In order for teams from Canada and the USA to appear on this list, they have to be approval by the [link url=" http://www.acpa-cpf.org/team_care/ ” target=”_blank”>American Cleft Palate-Craniofacial Association (ACPA). Look for a centre that has CFT listed beside its name, as some of the listed centres only have cleft palate teams (CPT).

Individuals with Pfeiffer syndrome may require a series of a dozen or more surgeries over the course of their childhood. Often the first skull surgery is as early as 3 months of age. This surgery usually involves releasing the sutures (skull joints) that have fused too early to allow room for the brain to grow. This also helps reduce the pressure within the brain, and reduces the chances of an intellectual impairment. This first surgery should be performed before 18 months of age.

The experience of children who have Pfeiffer syndrome can be variable. For some, the condition mainly causes cosmetic facial symptoms. Others may have severe symptoms affecting breathing, feeding, vision and brain development.

Individuals with Pfeiffer syndrome may require a series of a dozen or more surgeries over the course of their childhood. Often the first skull surgery is as early as 3 months of age. This surgery usually involves releasing the sutures (skull joints) that have fused too early to allow room for the brain to grow. This also helps reduce the pressure within the brain, and reduces the chances of an intellectual impairment. This first surgery should be performed before 18 months of age.

If the eyes are so prominent that the eyelids cannot close properly, lubrication may be necessary to protect the surface of the eyes. Surgeries to advance the face, performed at a later stage, can make more room for the eyes, and improve the cosmetic appearance of the face. The cosmetic result is usually not ‘perfect’ however significant improvement can be achieved.

Some children with Pfeiffer syndrome have developmental delays, and may require additional supports at school.

Planning around medical appointments and multiple surgeries may affect the whole family. The cosmetic differences that are part of Pfeiffer syndrome can be difficult for children and adults to cope with. Families may wish to teach their child’s educators and peers about the condition to promote acceptance and understanding of their child’s facial differences.

Surgical interventions, where necessary, are usually complete by late adolescence.

With proper treatment, most children with Pfeiffer syndrome will grow up to have normal intelligence and lead normal lives.

Pfeiffer syndrome is a rare genetic condition involving premature fusion of bones in the skull (craniosynostosis). Normally, the skull grows evenly at many fibrous joints (soft spots) as a child’s brain grows. If one or more of these fibrous joints fuses too early, this causes a misshapen head and characteristic facial features that may be apparent during infancy. The facial features that are characteristic of Pfeiffer syndrome include a prominent forehead, wide-set eyes (hypertelorism), protruding eyes (ocular proptosis), and flattened mid-face (mid-face hypoplasia). Surgery may be necessary to allow the brain and eyes enough room to grow.

Pfeiffer syndrome also affects the bones in the thumbs, big toes and elbows. The thumbs and big toes may be wider than usual and point outwards. The fingers and toes may be shorter than average, and the 2nd and 3rd fingers and toes may be partially webbed. Children with Pfeiffer syndrome may have hearing loss and some have dental problems. Individuals who are more severely affected may have intellectual disabilities and neurological complications.

Pfeiffer syndrome is inherited in an autosomal dominant manner. It affects about 1 in 100,000 individuals.

If you think you or your child may have Pfeiffer syndrome, talk to your doctor about a referral to a specialist who is familiar with the condition.

Pfeiffer syndrome is a genetic condition caused by a mutation (genetic change) in fibroblast growth factor receptor gene 1, FGFR-1 or fibroblast growth factor receptor gene 2, FGFR-2. These genes control the growth and maturation of cells in our bodies. Pfeiffer syndrome type 1 is associated with mutations in FGFR1 or FGFR2. Pfeiffer syndrome type 2 and type 3 are associated with mutations in FGFR2.

If the eyes are so prominent that the eyelids cannot close properly, lubrication may be necessary to protect the surface of the eyes. Surgeries to advance the face, performed at a later stage, can make more room for the eyes, and improve the cosmetic appearance of the face. The cosmetic result is usually not ‘perfect’ however significant improvement can be achieved.

Based on the presence and severity of the symptoms, Pfeiffer syndrome is divided into three clinical subtypes:

Type 1 "classic" Pfeiffer syndrome is considered mild compared to types II and III. In Pfeiffer syndrome type I infants have premature fusion of the skull bones (craniosynostosis) that causes the head to appear vertically elongated. Distinctive facial features may include a high full forehead; underdeveloped mid-facial regions (midface hypoplasia); widely spaced eyes (ocular hypertelorism); an underdeveloped upper jaw (hypoplastic maxilla) with a prominent lower jaw; and dental crowding. People with type I usually have normal intelligence and a good prognosis with a normal life span.

Type 2 typically involves more severe craniosynostosis, more severe hand and foot abnormalities and additional malformations of the limbs. Infants with type 2 have a form of craniosynostosis that causes the skull to have a tri-lobed appearance (called a cloverleaf skull deformity). This is often associated with an accumulation of fluid in the brain (hydrocephalus) which causes increased pressure on the brain. Distinctive facial features may include an abnormally high broad forehead; severe protrusion of the eyes (ocular proptosis); flattened midface (midface hypoplasia); a beak-shaped nose; and low-set ears. Infants may also have lack of mobility of the elbow joints and/or various abnormalities in some of the internal organs (visceral anomalies). Infants with type 2 often have intellectual disabilities and neurological problems due to severe brain involvement. The physical abnormalities associated with type 2 can lead to life-threatening complications without appropriate treatment.

Type 3 is similar to type 2 but without the cloverleaf skull deformity. The features associated with type 3 may include a shortened base of the skull; the abnormal presence of teeth at birth (natal teeth); protrusion of the eyes (ocular proptosis); and/or various anomalies of the internal organs. As in type 2 people with type 3 often have intellectual disabilities and severe neurological problems. There is overlap between the clinical subtypes.

The main purpose of genetic testing is to confirm a questionable clinical diagnosis (a diagnosis based on the symptoms). The genetic testing for Pfeiffer syndrome will often begin by testing two portions of FGFR2 called exons 8 and 10. 80% of mutations (genetic changes) in FGFR2 are found in these parts of the gene. If this comes back normal, other portions called exons 3, 5, 11, 14, 15, 16, and 17 can be tested, as another 10% of FGFR2 mutations are found within these sections. If the symptoms are mild genetic testing of the FGFR1 gene may be done.

If genetic testing has already found the cause of Pfeiffer syndrome in a parent, genetic testing can be performed during a pregnancy to determine whether the pregnancy is affected. This testing cannot however predict how severely the baby would be affected.

Preimplantation genetic diagnosis (PGD) is an option that would allow a couple where one person is affected with Pfeiffer syndrome (confirmed with a genetic test) to avoid passing it down to their children. In PGD the eggs are fertilized outside of the body (in vitro fertilization), then tested to see which ones have inherited Pfeiffer syndrome. This would allow parents to implant only those embryos that have not inherited the condition, in order to avoid passing it on to their children.

It is difficult to diagnose Pfeiffer syndrome on ultrasound before birth because the features can vary considerably. Occasionally it can be diagnosed before birth by ultrasound showing craniosynostosis (abnormally shaped head), hypertelorism (wide set eyes) with protruding eyes and broad thumbs.

If you are concerned about the risk of having a child with Pfeiffer syndrome and the options available, you may wish to speak to a certified genetic counselor, who can answer your questions and tailor the information to your specific situation. A list of genetic counselors is available on the National Society of Genetic Counselors website as well as on the Canadian Association of Genetic Counsellors website.

The treatment of Pfeiffer syndrome is directed toward the specific symptoms found in each individual. Pfeiffer syndrome cannot be cured, therefore therapies are aimed at improving the symptoms and problems caused by Pfeiffer syndrome.

The experience of children who have Pfeiffer syndrome can be variable. For some, the condition mainly causes cosmetic facial symptoms. Others may have severe symptoms affecting breathing, feeding, vision and brain development.

Several different investigations can be helpful to plan a child’s treatment:

The easiest way to learn more about studies and clinical trials in Pfeiffer syndrome is to talk to a genetic counselor, Pfeiffer syndrome doctor, or medical geneticist that is familiar with Pfeiffer syndrome. However, all the Pfeiffer syndrome studies looking at treatments and cures are also posted at clinicaltrials.gov where you can search for "Pfeiffer syndrome". Look for studies that list Pfeiffer syndrome as the condition as many listed in the search results may only be there because the FGFR-2 gene is being studied. Don’t limit your search to your state or country, many studies will pay for your travel if you would like to join a study.

When Pfeiffer syndrome (types 1, 2, and 3) is caused by a new mutation (de novo), the new mutation has usually occurred in the copy of the gene contributed by the father. There is a phenomenon known as the paternal age effect where the frequency of mutations new mutations in FGFR1 and FGFR2 in children increases with the age of their father.

It is important to remember that there is nothing a person can do to prevent or cause a new Pfeiffer syndrome causing mutation in their child. Also, while there is an association between de novo Pfeiffer syndrome and paternal age, a child with de novo Pfeiffer syndrome can be born to parents of any age. This is to say that an older father has a higher chance of having a child with de novo Pfeiffer syndrome than a younger father, however Pfeiffer syndrome is rare enough that the overall risk to each of them is still quite low.

Pfeiffer syndrome is inherited in an autosomal dominant manner. It is a dominant condition. A dominant condition, occurs when one altered copy of a gene is enough to cause the condition. Genes are the instructions for our bodies. They exist in pairs, contained inside of every cell. One copy from each pair is inherited from the mother, the other copy is inherited from the father. People with Pfeiffer syndrome have one normal copy of the associated gene and one altered copy. An alteration in a gene can also be called a mutation. They are the same thing. Pfeiffer syndrome can occur in one of two ways:

Pfeiffer syndrome can usually be diagnosed based on the presence of the following symptoms:

There are a couple of reasons that a child could have Pfeiffer syndrome, but neither parent is affected:

If you are unable to find a support group in your area or online that is helpful to you, you can start your own support group. First, talk to other support group leaders and see if they have helpful information. You also may want to look for resources that your group may need before you start your support group. If you want to start a support group online, you may be interested in using social media platforms such as Yahoo! Groups or Facebook to connect with others.

There are multiple sites where you can donate to organizations that work with Pfeiffer syndrome and other conditions that cause skeletal problems:
Donate at http://www.ccakids.com/pfeiffer-syndrome.html by clicking on the “Donate” button in the upper right corner.
Donate at https://www.mercy.net/practice/mercy-clinic-kids-plastic-surgery/pfeiffer-syndrome by clicking “Make a Donation” in the top part of the page.
Donate http://www.faces-cranio.org/Disord/Pfeiffer.htm by clicking on “GiveDirect” on the right side of the page.

Care of people with Pfeiffer syndrome requires many different doctors. A care team typically involves plastic surgeons, neurosurgeons, physicians who diagnose and treat disorders of the ears, nose, and throat (otolaryngologists), and dentists as well as specialists who assess and treat hearing problems (audiologists), speech pathologists, social workers, developmental pediatricians, and medical geneticists.
To find a treatment center for Pfeiffer syndrome, you can go to http://www.faces-cranio.org/MedCent.htm to find a cranio-facial specialist near you.

Pfeiffer syndrome occurs in about 1 in 100,000 people.

If you live in a large city there might be other people with Pfeiffer syndrome in your area. You can search online for a local support group. You might also want to ask your genetic counsellor or craniofacial specialist if they know any other families with whom they could put you in contact.

Because Pfeiffer syndrome is rare, there may not be others with Pfeiffer syndrome living near to you, especially if you live in a smaller town for city. In this case, online support groups would be a good way to contact other people living with Pfeiffer syndrome.

Pfeiffer syndrome is also known as:

There are several support groups for families of children with Pfeiffer syndrome:

Born a Hero fights to improve the life of patients with Pfeiffer syndrome and their families. They provide educational resources and support. – a ThinkGenetic Advocacy Partner

Pfeiffer Syndrome Support Group is a place for parents of children with Pfeiffer Syndrome to join with other parents and learn about what they can expect for the future of their children. This group includes parents of children with and young adults with Pfeiffer Syndrome. To join, send an e-mail request to [link url="[email protected]” target=”_blank”>[email protected]

FACES: The National Craniofacial Association has newsletters and networking available at [link url="www.faces-cranio.org” target=”_blank”>www.faces-cranio.org.

"Pfeiffer Syndrome" (https://www.facebook.com/groups/2314394613/) is a closed group on Facebook that must approve your request to join. They say "This is a group to celebrate the families dealing with things that no one should ever have to deal with. It is a group to celebrate the families dealing with Pfeiffer Syndrome."

The Children’s Craniofacial Association (a ThinkGenetic Advocacy Partner) has many resources on their website for "empowering and giving hope to individuals and families affected by facial differences."

There are other conditions that cause problems in growth of bones in the head. Pfeiffer syndrome needs to be distinguished from Saethre-Chotzen syndrome, Antley-Bixler syndrome, Baller-Gerold syndrome, Carpenter syndrome, Craniofrontonasal syndrome, Greig cephalopolysyndactyly, Opitz trigonencephaly C syndrome, Boston-type craniosynostosis, Philadelphia-type craniosynostosis, Shprintzen-Goldberg syndrome, Crouzon syndrome, and Apert syndrome, all of which have early joining of skull bones or unusual facial features as a symptom.

A doctor specializing in genetics or conditions affecting the skull can help to determine if you or your family member has Pfeiffer syndrome or a similar condition affecting the skull. Sometimes this can be determined from the symptoms alone, other times genetic testing is necessary.