Table 1. Some craniosynostoses associated with de novo mutations in fibroblast growth factor receptor genes.

Syndrome	Nervous System Phenotype	Genotype
Apert Syndrome (Moloney et al. 1996; Tolarova et al.1997; Yu et al. 2000)	Developmental disorder including craniosynostosis, with displacement of the frontal and parietal bone centers, midfacial hypoplasia, facial asymmetry, depressed nasal ridge, and mental retardation. Can include hydrocephalus and hearing difficulties.	10q25-q26. One of two substitutions, both C→G in the fibroblast growth factor receptor 2 gene (FGFR2) > 98% de novo in association with paternal age. Approximately 5% of craniosynostoses.
Pfeiffer Syndrome (Plomp et al. 1998; Robin et al. 1998; Glaser et al. 2000)	Type 1 is an autosomal dominant condition including craniofacial abnormalities, coronal craniostosis, and midface hypoplasia. Type 2 (always de novo) includes a cloverleaf skull, deafness, and midface hypoplasia. Severe cases have significant cognitive impairment.	8p11.2,10q25-26. Mutation of FGFR2 or FGFR1 genes. Approximately 70% of cases are sporadic.
Crouzon Syndrome (Glaser et al. 2000; Yu et al. 2000)	Includes craniosynostosis, hypertelorism, midface hypoplasia, and exophthalmos. Premature closure of some cranial sutures affects brain growth. Includes cognitive difficulties and retardation.	10q24 heterogeneous FGFR2 mutations. Birth prevalence is 16/million with approximately 30%–60% of cases from de novo events.
Thanatophoric Dysplasia (Orioli et al. 1995; Yu et al. 2000)	Characterized by multiple severe bone abnormalities. Includes prominent forehead, hypertelorism, depressed nasal bridge, and a cloverleaf skull. Surviving cases show dramatic growth failure, hydrocephalus, and severe developmental delay.	All cases are de novo and often do not survive. Result from missense mutations in the FGFR3.