Crouzon syndrome, an autosomal dominant condition characterized by craniosynostosis, ocular proptosis and midface hypoplasia, is associated with mutations in fibroblast growth factor receptor 2 (FGFR2) (refs 1-3). For example, we have identified 10 different mutations in the FGFR2 extracellular immunoglobulin III (IgIII) domain in 50% (16/32) of our Crouzon syndrome patients. All mutations described so far for other craniosynostotic syndromes with associated limb anomalies--Jackson-Weiss, Pfeiffer, and Apert--also occur in the extracellular domain of FGFR2, as well as FGFR1 for Pfeiffer syndrome. In contrast, only FGFR3 mutations have been reported in dwarfing conditions--achondroplasia, thanatophoric dysplasia, and hypochondroplasia. For achondroplasia, greater than 99% of mutations occur in the FGFR3 transmembrane domain. We now report the unexpected observation of a FGFR3 transmembrane domain mutation, Ala391Glu, in three unrelated families with Crouzon syndrome and acanthosis nigricans, a specific skin disorder of hyperkeratosis and hyperpigmentation. The association of non-dwarfing and even non-skeletal conditions with FGFR3 mutations reveals the potential for a wide range of FGFR pleiotropic effects as well as locus heterogeneity in Crouzon syndrome. Our study underscores the biologic complexity of the FGFR gene family.
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"Previously, we have characterized the dimerization of FGFR3 in the presence of the A391E mutation that causes a craniosynostosis, Crouzon syndrome with acanthosis nigricans . We have shown that the mutation stabilizes the unliganded FGFR3 dimer by − 1.4 kcal/mol in plasma-membrane-derived vesicles produced with the DTT/formaldehyde vesiculation buffer . "
"Additional recognizable syndromes such as Beare– Stevenson, Crouzon with acanthosis nigricans, and Antley‐Bixler (caused by mutations of FGFR2 and POR) have also been described [Beare et al., 1969; Stevenson et al., 1978; Meyers et al., 1995] "
"Mutation of the FGFR gene is also responsible for other craniosynostosis, such as Apert's, Pfeiffer's, Jackson-Weiss' and Saethe-Chotzen's syndromes.14 Rarely, acanthosis nigricans may coexist with CS in childhood and is caused by mutation in the FGFR3 gene (locus 4p16.3)15 "
[Show abstract][Hide abstract] ABSTRACT: Crouzon's syndrome (CS) is a rare autosomal dominant condition with multiple mutations of the fibroblast growth factor receptor (FGFR2) gene, which accounts for 4.8% of all cases of craniosynostosis. It is characterized by premature closure of cranial sutures, cranial deformities, midface hypoplasia, relative mandibular prognathism, hypertelorism, proptosis, strabismus and short upper lip, crowding of teeth, pseudocleft or sometimes cleft palate and other associated abnormalities. The CS can vary in severity from mild presentation to severe forms involving multiple cranial sutures. We report a case of CS in 11-year-old boy.
How to cite this article: Kumar GR, Jyothsna M, Ahmed SB, Lakshmi KS, Crouzon's Syndrome: A Case Report. Int J Clin Pediatr Dent 2013;6(1):33-37.