Pfeiffer syndrome is divided into three subtypes with types 2 and 3 being more common and severe than type 1, which has a better overall prognosis. Type 1 is characterized by craniosynostosis, midface hypoplasia, broad and medially deviated thumbs and great toes, and varying degrees of brachydactyly. Other findings may include hearing loss and/or hydrocephalus. Intellect is typically normal. Types 2 and 3 have more extreme craniosynostosis, significant proptosis, and broad and medially deviated thumbs and great toes. Other findings may include choanal stenosis/atresia, laryngotracheal abnormalities, hydrocephalus, and seizures. In addition type 2 may have cleft palate. Developmental delay/intellectual disability is common in both.
Pfeiffer syndrome is inherited in an autosomal dominant manner. Variants may be inherited from an affected parent or may be de novo. Approximately 5% of Pfeiffer syndrome type 1 cases are due to the p.Pro252Arg mutation in the FGFR1 gene, while the remaining 95% of cases are due to sequence variants in the FGFR2 gene. This laboratory performs targeted variant analysis for p.Pro252Arg in the FGFR1 gene as well as Sanger sequencing of the FGFR2 gene.