Pfeiffer syndrome is clinically and genetically heterogeneous. Three clinical 
subtypes have been delineated based on the severity of acrocephalysyndactyly and 
associated manifestations. Severe cases are usually sporadic and caused by a 
number of different mutations in exons IIIa and IIIc of the fibroblast growth 
factor receptor 2 (FGFR2) gene. Mild cases are either sporadic or familial and 
are caused by mutations in FGFR2 or FGFR1, respectively. We report on two 
individuals with different novel de novo mutations in FGFR2. The first is a 
17-year-old male who has a severe phenotype, within the spectrum of subtype 1 
including severe ocular proptosis, elbow ankylosis, visceral anomalies, and 
normal intelligence. This patient was found to have a novel complex mutation at 
the 3' acceptor site of exon IIIc of FGFR2, denoted as C952-3 del10insACC. The 
other patient, a 2-year-old female, has a mild phenotype, typical of the classic 
subtype 1 including brachycephaly with coronal synostosis and hypertelorism. She 
was also found to have a mutation at the 3' acceptor site (the same splice site) 
of exon IIIc of FGFR2, a point mutation designated as 952-1G-->A. Speculation on 
the molecular mechanisms that cause severe and mild phenotypes is presented in 
relation to these two cases.