Pfeiffer Syndrome

• Pfeiffer syndrome facts
• What is Pfeiffer syndrome?
• What causes Pfeiffer syndrome?
• What are the signs and symptoms of Pfeiffer syndrome?
• How common is Pfeiffer syndrome?
• How is Pfeiffer syndrome diagnosed?
• Is there any treatment for Pfeiffer syndrome?
• What other disorders are related to Pfeiffer syndrome?
• What is the life expectancy of an individual with Pfeiffer syndrome?

• Pfeiffer syndrome is a genetic disorder that results in abnormalities of the skull and facial bones as well as changes in the fingers and toes.
• Pfeiffer syndrome is subdivided into three types.
  • People with Type I Pfeiffer syndrome usually have a normal lifespan and typical intelligence.
  • Those with Types II and III Pfeiffer syndrome have more severe defects that can impair brain development and function.
• There is no specific treatment for Pfeiffer syndrome. Treatment is directed at improving the individual's symptoms.
• Pfeiffer syndrome is associated with mutations (changes) in the FGFR genes.
• Pfeiffer syndrome affects about 1 out of every 100,000 people.
• Pfeiffer syndrome can be inherited or can occur due to a new mutation, or change, in the involved gene. In cases of severe Pfeiffer syndrome, a new mutation is typically the cause.

Pfeiffer syndrome is a rare genetic disorder characterized by premature fusion of certain skull bones (craniosynostosis) and other birth defects in the hands and feet. The abnormality of the skull bones causes changes in the shape of the face and head. There are three subtypes of the syndrome, with Types II and II being the most severe.

Pfeiffer syndrome has also been referred to as acrocephalosyndactyly type V, ACSV, craniofacial-skeletal-dermatologic syndrome, and Noack syndrome.

Pfeiffer syndrome is inherited as an autosomal dominant genetic disorder, meaning that only a single copy of an abnormal gene is necessary to cause the condition. The abnormal gene can be inherited from either parent or be a result of a new mutation (change in a gene) in the affected individual. Almost all cases of Pfeiffer syndrome type II and type III originate from new mutations because the parents are unaffected.

• Pfeiffer syndrome type I is associated with mutations in genes known as FGFR1 and FGFR2.
• Pfeiffer syndrome type II and type III are associated with mutations in FGFR2.
• Older age in the father is a known risk factor for acquiring Pfeiffer syndrome in the offspring due to new mutations.

Signs and symptoms of Pfeiffer syndrome include:

• Bulging eyes
• Wide-set eyes
• High forehead
• Beaked nose
• Underdevelopment of the upper jaw
• Prominent lower jaw
• Protrusion of the eyes
• Hearing loss (in over 50% of those affected)
• Short fingers and toes (brachydactyly)
• Webbing or fusion between the digits (syndactly)
• Dental problems
• Wide thumbs and big toes that bend away from the other digits
• Cloverleaf-shaped head (in Type II Pfeiffer syndrome)

People with Type I Pfeiffer syndrome typically have normal intelligence. Types II and III of Pfeiffer syndrome are more severe. People with types II and III of Pfeiffer syndrome usually have problems with brain development. This can cause limitation of brain growth and developmental delays.

Pfeiffer syndrome affects around 1 out of every 100,000 people.

Pfeiffer syndrome is diagnosed by the presence of the characteristic birth defects. If the diagnosis is uncertain, genetic testing can be done to identify changes in the FGFR1 and/or FGFR2 genes.

There is no treatment that can reverse Pfeiffer syndrome, but treatments are available that address each individual's specific symptoms. Treatments may be needed from a variety of specialists, including surgeons, pediatricians, otolaryngologists (ENT specialists), neurologists, or others. Reconstructive surgeries can help overcome some of the physical defects associated with the syndrome.

There is a spectrum of disorders associated with changes to the FGFR genes that results in facial defects. These conditions include Pfeiffer syndrome and the following:

• Apert syndrome
• Crouzon syndrome
• Beare-Stevenson syndrome
• FGFR2-related isolated coronal synostosis
• Jackson-Weiss syndrome
• Crouzon syndrome with acanthosis nigricans (AN)
• Muenke syndrome

Most people with Type I Pfeiffer syndrome have a normal life span. People with Types II and III have severe disease and may develop complications that shorten their life expectancy.