Pfeiffer Syndrome

Pfeiffer syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face. Pfeiffer syndrome also affects bones in the hands and feet.

Other Names

• acrocephalosyndactyly, type V
• ACS5
• ACS V
• Craniofacial-skeletal-dermatologic dysplasia
• Noack syndrome

Types

Pfeiffer syndrome is divided into three subtypes. Type 1, also known as classic Pfeiffer syndrome, has symptoms as described above. Most individuals with type 1 Pfeiffer syndrome have normal intelligence and a normal life span. Types 2 and 3 are more severe forms of Pfeiffer syndrome that often involve problems with the nervous system. The premature fusion of skull bones can limit brain growth, leading to delayed development and other neurological problems. Type 2 is distinguished from type 3 by the presence of a cloverleaf-shaped head, which is caused by more extensive fusion of bones in the skull.

Signs and Symptoms

Many of the characteristic facial features of Pfeiffer syndrome result from premature fusion of the skull bones. Abnormal growth of these bones leads to bulging and wide-set eyes, a high forehead, an underdeveloped upper jaw, and a beaked nose. More than half of all children with Pfeiffer syndrome have hearing loss; dental problems are also common.

In people with Pfeiffer syndrome, the thumbs and great toes are wide and bend away from the other digits. Unusually short fingers and toes (brachydactyly) are also common, and there may be some webbing or fusion between the digits (syndactyly).

Causes

Pfeiffer syndrome results from mutations in the FGFR1 or FGFR2 gene. These genes provide instructions for making proteins known as fibroblast growth receptors 1 and 2. Among their multiple functions, these proteins signal immature cells to become bone cells during embryonic development. A mutation in either the FGFR1 or FGFR2 gene alters protein function and causes prolonged signaling, which can promote the premature fusion of skull bones and affect the development of bones in the hands and feet.

Type 1 Pfeiffer syndrome is caused by mutations in either the FGFR1 or FGFR2 gene. Types 2 and 3 are caused by mutations in the FGFR2 gene, and have not been associated with changes in FGFR1.

Chances of Developing Pfeiffer Syndrome

Pfeiffer syndrome affects about 1 in 100,000 individuals.

Genetics

Pfeiffer syndrome results from mutations in the FGFR1 or FGFR2 gene.

Heredity

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Other Resources

• Gene Reviews
• MedlinePlus Encyclopedia: Craniosynostosis
• MedlinePlus Encyclopedia: Webbing of fingers or toes
• Educational resources
• Patient support.
• MedlinePlus - Health information (4 links)
• Additional NIH Resources - National Institutes of HealthNational Institute of Neurological Disorders and Stroke: Craniosynostosis Information Page
• Educational resources - Information pages (7 links)
• Patient support - For patients and families (6 links)
• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• OMIM - Genetic disorder catalog