Familial Pfeiffer Syndrome: Variable Manifestations and Role of Multidisciplinary Team Care

Area of Science:

• Genetics
• Craniofacial Biology
• Medical Genetics

Background:

• Pfeiffer syndrome is an autosomal dominant craniofacial disorder characterized by coronal suture synostosis, midface retrusion, and limb abnormalities.
• Type I Pfeiffer syndrome is typically linked to mutations in the Fibroblast Growth Factor Receptor 1 (FGFR1) gene.
• Clinical manifestations can be highly variable, even within families, and may not always include craniosynostosis.

Purpose of the Study:

• To investigate the genetic basis and clinical spectrum of Pfeiffer syndrome in a multi-generational family.
• To analyze the impact of a specific FGFR1 mutation (c.755C>G, p.Pro252Arg) on phenotypic expression across generations.
• To propose a management guideline for familial Pfeiffer syndrome.

Main Methods:

• Clinical evaluation of affected family members across three generations.
• Genetic analysis to identify and confirm the specific FGFR1 mutation.
• Phenotypic correlation between genotype and clinical manifestations, focusing on cranial involvement.

Main Results:

• Identified an identical FGFR1: c.755C>G (p.Pro252Arg) mutation in all affected family members across three generations.
• Observed a significant reduction in cranial involvement, specifically craniosynostosis, in the youngest generation.
• Demonstrated variable expressivity of Pfeiffer syndrome, with the same mutation leading to different clinical presentations.

Conclusions:

• The FGFR1: c.755C>G (p.Pro252Arg) mutation is causative for Pfeiffer syndrome in this family.
• Phenotypic variability, including the absence of cranial involvement in some individuals, is a key feature.
• A structured management guideline is proposed for familial Pfeiffer syndrome, considering genotype-phenotype correlations.