Crouzon syndrome (CS), which results from fibroblast growth factor receptor 2 mutations, is associated with craniosynostosis, exophthalmos, and other symptoms.
The most common craniosynostosis syndromes include Apert (FGFR2), Crouzon (FGFR2), Muenke (FGFR3), Pfeiffer (FGFR1 and FGFR2), and Saethre-Chotzen (TWIST).
Fibroblast growth factor receptor 2 (FGFR2) <sup>C342Y/+</sup> mutation is a known cause of Crouzon syndrome that is characterised by craniosynostosis and midfacial hypoplasia.
FGFR2 encodes a fibroblast growth factor receptor whose mutations are responsible for the Crouzon syndrome, involving craniosynostosis and facial dysostosis with shallow orbits.
<b>Background:</b> Apert syndrome is considered as one of the most common craniosynostosis syndromes with a prevalence of 1 in 65,000 individuals, and has a close relationship with point mutations in FGFR2 gene.
The genes related to the pathogenesis of the craniosynostoses itself are those encoding transcription factors, e.g., TWIST1, MSX2, EN1, and ZIC1, and proteins involved in osteogenic proliferation, differentiation, and homeostasis, such as FGFR1, FGFR2, RUNX2, POR, and many others.
Although FGFR2 gene mutations and polymorphisms have been studied in various ethnic groups, we report a mutation of FGFR2 in two different Chinese patients with two different types of syndromic craniosynostosis.
These findings, together with previous data, imply that the same FGFR2 mutations can be associated with a wide range of phenotypes including clinically different forms of syndromic craniosynostosis and apparently normal phenotype, depending on other (epi)genetic and environmental factors.
Here we examine integration of brain and skull in two mouse models for craniosynostosis: one carrying the FGFR2c C342Y mutation associated with Pfeiffer and Crouzon syndromes and a mouse model carrying the FGFR2S252W mutation, one of two mutations responsible for two-thirds of Apert syndrome cases.
In addition, we describe findings from a sequence analysis of all coding exons and exon/intron boundaries of FGFR2 performed on 124 patients with syndromic craniosynostosis.
Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported.
Of note, tracheal cartilaginous sleeves have been reported in other FGFR2-related craniosynostosis syndromes, and are associated with 90% risk of death by two years of age without tracheostomy.
Since our patient shows typical radiological findings of Pfeiffer syndrome in hands and feet but at the same time lacks several characteristic features such as clinical signs of craniosynostosis and prominent eyes we suggest introducing the term "FGFR2 associated phenotypes" for similar cases.
Here we investigate growth of the skull in two inbred mouse models each carrying one of two gain-of-function mutations in FGFR2 on neighboring amino acids (S252W and P253R) that in humans cause Apert syndrome, one of the most severe FGFR-related craniosynostosis syndromes.
We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis.
Besides the cranial phenotype, brain dysmorphologies are present and are not seen in other FGFR2-asociated craniosynostosis, such as Crouzon syndrome (CS).