Overview Of Pfeiffer Syndrome Type I
Pfeiffer syndrome type I is a genetic disorder that involves the premature fusion of certain skull bones (craniosynostosis).
This fusion prevents the skull from growing normally, and it affects the shape of the head and bones in both the feet and hands.
The abnormal growth of bones in the skull causes a high forehead, bulging wide-set eyes, a beaked nose, and an underdeveloped upper jaw. Hearing loss and dental problems are also evident in over 50 percent of children with Pfeiffer syndrome.
The thumbs and big toes are wide and bend away from the other digits in people with Pfeiffer syndrome. Also common are unusually short fingers and toes (brachydactyly) while there may be some webbing or fusion between the digits (syndactyly).
Pfeiffer syndrome has three subtypes:
Type 1, also known as classic Pfeiffer syndrome, has the symptoms above. People with type 1 Pfeiffer syndrome have normal intelligence and a normal life span.
Types 2 and 3 are more severe. They generally involve nervous system issues. The premature fusion of skull bones impedes brain growth, leading to neurological issues such as delayed development.
Individuals with type 2 or 3 can also have abnormalities of the face and airways, which can cause life-threatening breathing difficulties and the fusion of the bones (ankylosis) in the elbow or other joints, limiting mobility. The presence of a cloverleaf-shaped head, caused by a more extensive fusion of bones in the skull, distinguishes type 2 from type 3.
Commonly Associated With
- Acrocephalosyndactyly, type V
- ACS V
- Noack syndrome
- craniofacial-skeletal-dermatologic dysplasia
Causes Of Pfeiffer Syndrome Type I
The most common cause of Pfeiffer syndrome is mutations in the FGFR2 gene. FGFR1 gene mutations cause a small percentage of type 1 Pfeiffer syndrome cases. Mutations in this gene are not associated with type 2 or 3.
The FGFR1 and FGFR2 genes give instructions for the production of proteins known as fibroblast growth factor receptors 1 and 2, respectively. During embryonic development, these proteins signal immature cells to become bone cells When there is a mutation in the FGFR1 or FGFR2 gene, the function of the respective proteins changes, causing prolonged signaling. This prolonged signaling can cause the premature fusion of skull bones and affect bone development in the feet and hands.
One in 100,000 individuals are affected by Pfeiffer syndrome. Pfeiffer syndrome is inherited in an autosomal dominant pattern. This means one copy of the altered gene in each cell is sufficient to cause the disorder.