Clinicogenetic Study of Turkish Patients With Syndromic Craniosynostosis and Literature Review

• Published in: Pediatric neurology 2014-05, Vol.50 (5), p.482-490
• Main Authors: Nur, Banu G., MD, Pehlivanoğlu, Suray, PhD, Mıhçı, Ercan, MD, Çalışkan, Mualla, PhD, Demir, Durkadın, PhD, Alper, Özgül M., PhD, Kayserili, Hülya, MD, Lüleci, Güven, PhD
• Format: Article
• Language: English
• Subjects: Acrocephalosyndactylia - genetics; Adolescent; Adult; Apert syndrome; Child; Child, Preschool; Craniofacial Dysostosis - genetics; Craniosynostoses - genetics; craniosynostosis; Crouzon syndrome; DHPLC; DNA Mutational Analysis; Exons; Female; Humans; Infant; Male; Mutation; Neurology; Pediatrics; Pfeiffer syndrome; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Young Adult
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2014.01.023

Abstract Background Fibroblast growth factor receptor 2 mutations have been associated with the craniosynostotic conditions of Apert, Crouzon, Pfeiffer, Saethre-Chotzen, Jackson-Weiss, Beare-Stevenson cutis gyrata, and Antley-Bixler syndromes in various ethnic groups. Methods Thirty-three unrelated Turkish patients (12 with Apert syndrome, 14 with Crouzon syndrome, six with Pfeiffer syndrome, and one with Saethre-Chotzen syndrome) and 67 nonsyndromic craniosynostosis patients were screened for mutations in exons IIIa and IIIc of the FGFR2 gene by denaturing high-performance liquid chromatography and confirmed by direct sequencing. Results We detected several pathogenic mutations in 11/33 (33%) patients with Apert syndrome (four with p.Pro253Arg; seven with p.Ser252Trp) and 8/33 (24%) patients with Crouzon syndrome (three with p.Trp290Arg, one with p.Cys342Tyr, p.Cys278Phe, p.Gln289Pro, and a novel p.Tyr340Asn mutation) and five (15%) with Pfeiffer syndrome (p.Cys342Arg, p.Pro253Arg, p.Trp290Arg, and p.Ser351Cys). No FGFR2 gene mutation was detected in any of the patients with Saethre-Chotzen syndrome and nonsyndromic craniosynostosis. Conclusions Our results indicate that the majority of Turkish patients with syndromic craniosynostosis have detectable genetic changes with an overall frequency of 72.7%. Because this is the first molecular genetic report from a Turkish cohort, the identified spectrum profile of FGFR2 mutations of the syndromic craniosynostotic patients would be very helpful for understanding the genotype–phenotype relationship and has a great value for diagnosis, prognosis, and genetic counseling.