Phenotypic variability of syndromic craniosynostosis caused by c.833G > T in FGFR2: Clinical and genetic evaluation of eight patients from a five‐generation family. Issue 4 (2nd March 2022)

• Record Type: Journal Article
• Authors: Wei, Xianda; Huang, Guori; Gui, Baoheng; Xie, Bobo; Chen, Shaoke; Fan, Xin; Chen, Yujun
• Is Part Of: Molecular genetics & genomic medicine. Volume 10:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-02
• Subjects: craniosynostosis -- Crouzon syndrome -- FGFR2; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1901
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Objective: Craniosynostosis is the result of the early fusion of cranial sutures. Syndromic craniosynostosis includes but not limited by Crouzon syndrome and Pfeiffer syndrome. Considerable phenotypic overlap exists among these syndromes and mutations in FGFR2 may cause different syndromes. This study aims to investigate the explanation of the phenotypic variability via clinical and genetic evaluation for eight patients in a large pedigree. Methods: For each patient, comprehensive physical examination, cranial plain CT scan with three‐dimensional CT reconstruction (3D‐CT), and eye examinations were conducted. Whole exome sequencing was applied for genetic diagnosis of the proband. Variants were analyzed and interpreted following the ACMG/AMP guidelines. Sanger sequencing was performed to reveal genotypes of all the family members. Results: A pathogenic variant in the FGFR2 gene, c.833G > T (p.C278F), was identified and proved to be co‐segregate with the disease. Some symptoms of head, hearing, vision, mouth, teeth expressed differently by affected individuals. Nonetheless, all the eight patients manifested core symptoms of Crouzon syndrome without abnormality in the limbs, which could exclude diagnosis of Pfeiffer syndrome. Conclusion: We have established clinical and genetic diagnosis of Crouzon syndrome for eight patients in a five‐generation Chinese family. Variability of clinical features among these familial patients was slighter than that in previously reported sporadic cases. Abstract : Clinical and genetic evaluations were performed for eight patients in a large Chinese pedigree. All the patients manifested core symptoms of Crouzon syndrome without abnormality in the limbs. A pathogenic variant in the FGFR2 gene, c.833G > T (p.C278F), was identified and proved to be co‐segregate with the disease. Our findings may facilitate diagnosis and genetic counseling of syndromic craniosynostosis.