TABLE 1.
Molecular and Phenotypic Information Pertaining to Apert, Crouzon, Muenke, and Pfeiffer Syndromes.
| Genes Involved (no. of Known Mutations) | Syndrome | Birth Prevalence per 1,000,000 births | Clinical Craniofacial Phenotypes | Clinical Limbs Phenotypes | FGFR Functional Domain |
|---|---|---|---|---|---|
| FGFR1(1) | Pfeiffer | 0.5 (Robin et al., 1998; Vogels and Fryns, 2006) | Craniosynostosis, midfacial hypoplasia, ocular proptosis, hypertelorism | Broad first digits, brachydactyly, variable syndactyly | IgII-IgIII linker region |
| FGFR2 (2a) | Apert | 10–15.5 (Cohen et al., 1992; Robin et al., 1998) | Coronal craniosynostosis, midfacial hypoplasia, sagittal and metopic sutural agenesis, acrobrachycephaly, ocular proptosis, hypertelorism, highly arched and constricted palate | Hands and feet syndactyly | IgII-IgIII linker region |
| FGFR2 (40) | Crouzon | 15 (Cohen and Kreiborg, 1992) | Craniosynostosis midfacial hypoplasia, ocular proptosis, hypertelorism, arched palate | Normal | IgIII domainb |
| FGFR2 (29) | Pfeiffer | 9 (Robin et al., 1998; Vogels and Fryns, 2006) | More severe craniosynostosis, ocular propotosis and midfacial hypoplasia than FGFR1-related Pfeiffer, hypertelorism | Broader thumbs than FGFR1-related Pfeiffer, broad toes, brachydactyly, variable syndactyly | IgIII domainb |
| FGFR3 (1) | Muenke | 33.5 (Wilkie et al., 2010) | Coronal craniosynostosis, highly arched palate, variable facial dymorphisms | Variable carpal and tarsal fusion, variable broad great toes | IgII-IgIII linker region |
a
Apert syndrome can be rarely caused by Alu insertion (Oldridge et al., 1999).
b
About 15% of FGFR2 mutations associated with Pfeiffer or Crouzon syndromes have been identified within IgII, IgII-IgIII linker region, and the tyrosine kinase domain (Wilkie, 2005; Passos-Bueno et al., 2008).