These two transmembrane proteins are two of four fibroblast growth factor receptors involved in osteoblast differentiation during embryonic development; mutations amongst these receptors are involved in several genetic disorders.There are 40 known mutations, most of which are caused by a missense mutation. FGFR2 is the most commonly mutated gene, a missense at cysteine 342 in exon 9, which creates a gain-of-function. The FGFR2lllc isoform, created via alternative splicing of exon 3 of the FGFR2 gene, uses exon 9 and is used in mesenchymal stem cells to control ossification. However, the mutation constitutively activates the transmembrane protein via a disulfide bond formed incorrectly due to the loss of cysteine 342. FGFR3 is expressed more in the frontal bones during embryonic development, guiding cranial bone development. A point mutation causes constitutive activation of tyrosine in the activation loop, located in the cytosolic region of the protein, leading to accelerated differentiation of frontal osteoblasts, resulting in premature fusion of frontal cranial bones. Diagnosis
Diagnosis of Crouzon syndrome usually can occur at birth by assessing the physical appearance of the infant. Further analysis, including radiographs, magnetic resonance imaging (MRI) scans, genetic testing and CT scans can be used to confirm the diagnosis of Crouzon syndrome. Treatment
Surgery is typically used to prevent the closure of sutures of the skull from damaging the brains development. Without surgery, blindness and intellectual disability are typical outcomes. To move the orbits forward, surgeons expose the skull and orbits and reshape the bone.
To treat the midface deficiency, surgeons can move the lower orbit and midface bones forward.People with Crouzon syndrome tend to have multiple sutures involved, most specifically bilateral coronal craniosynostoses, and either open vault surgery or strip craniectomy (if the child is under 6 months) can be performed. In the latter scenario, a helmet is worn for several months following surgery.Once treated for the cranial vault abnormalities, Crouzon patients generally go on to live a normal lifespan. Epidemiology
Incidence of Crouzon syndrome is currently estimated at 1.6 out of every 100,000 people. It is the most common craniostenosis syndrome. History
Crouzon syndrome was first described by Octave Crouzon in 1912. He noted the affected patients were a mother and her daughter, implying a genetic basis. See also
Apert syndrome
Treacher Collins syndrome
Hearing loss with craniofacial syndromes

References
External links

Crouzon syndrome on Genetics Home Reference from U.S. National Library of Medicine & National Institutes of Health
GeneReviews/NIH/NCBI/UW entry on FGFR-Related Craniosynostosis Syndromes