Pfeiffer syndrome is a genetic disorder that affects 1 in 100,000 births and is characterised by the premature fusion of skull bones.
Pfeiffer syndrome causes a number of skull bones to fuse early on in development which means that the skull and face are prevented from growing normally.
Characteristics of the syndrome include:
- Skull does not grow normally
- Bulging wide-set eyes - these are caused by shallow eye sockets
- High forehead
- Underdeveloped upper jaw
- Hearing loss
- Dental problems
- Wide, short thumbs and unusually large toes
Possible webbing of hands and feet, and syndactyly (fused digits)
Genetics of Pfeiffer Syndrome
Pfeiffer syndrome is caused by mutations in two genes known as FGFR1 and FGFR2 - where the initials stand for fibroblast growth factor receptor. Each of these genes codes for a protein that is a member of the fibroblast growth factor receptor family.
The proteins have many roles in the body including cell signalling, and during embryogenesis they signal immature cells to form bone cells. However, if the genes are mutated the protein function is altered and the signalling is protracted which causes the bones cells to mature earlier than they would otherwise. This also promotes the premature fusion of skull bones.
There are three subtypes of Pfeiffer syndrome - types 1,2, and 3. Individuals with type 1 tend to have normal intelligence and enjoy a normal lifespan.
Types 2 and 3 are more severe forms of the disease and the premature fusion of skull bones can limit brain growth which can lead to delayed development and neurological problems.
Pattern of Inheritance
Pfeiffer syndrome follows an autosomal dominant pattern of inheritance which means that an individual needs to inherit just one abnormal copy of FGFR1 or FGFR2 to develop the disease.
If one parent already has the condition then there is a 50% chance that this will be passed on to any offspring. The disease can also be the result of a spontaneous genetic mutation i.e. it is not inherited from either parent.
The general treatment plan for children with Pfeiffer syndrome is multiple stage surgery that will usually start in the first year of life. The skull can be remodelled to allow room for the brain to grow and expand. This may need to be repeated on several occasions as the child develops.
Further treatment involves managing the symptoms.
The prognosis for people with Pfeiffer syndrome can be extremely good, especially with the skill of reconstructive surgeons. Overall, individuals with type 1 tend to have a better prognosis than individuals with types 2 and 3.