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.
In addition to its helpful effects in treating AU, it can have side effects that can be very serious, such as severe dermatitis.Topical and intralesional corticosteroids, such as clobetasol propionate, have also shown to be an effective treatment for AT and AU patients. A controlled study comprising 28 patients found positive terminal hair growth in eight of the patients (28.5%) using a 0.05% clobetasol propionate ointment. This is very similar to the results obtained from immunotherapy treatment trials. Additionally, studies suggest that intralesional applications are much more effective than topical applications of steroids. However, the main side effect is increased risk of cutaneous atrophy at the site of treatment; folliculitis is also an occasional complication.Janus kinase inhibitors, previously used in the treatment of cancer and other diseases, such as arthritis, have successfully shown to be effective in the initial trials of treatment for alopecia patients. Multiple cases of treatments have been successful, one of them being of a 22-year-old man with a history of AU and atopic dermatitis (AD). This man was treated with JAK inhibitor tofacitinib, and after ten months, he experienced hair regrowth on all of his affected body parts and subsequent improvement of his AD. Current research and findings suggest that systemic JAK inhibitors eliminate and prevent the development of AA, while topical JAK inhibitors promote hair regrowth and reverse the established disease. Many clinical trials are ongoing involving JAK inhibitors such as ruxolitinib and tofacitinib. See also
Alopecia areata
Alopecia totalis

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