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Phenotypic diversity in patients with craniosynostoses unrelated to Apert syndrome: the role of fibroblast growth factor receptor gene mutations.
J Neurosurg. 2005 Jan; 102(1 Suppl):23-30.JN

Abstract

OBJECT

The goal of this study was to elucidate the genotype-phenotype relationship in syndromic craniosynostoses by analyzing the mutations of the fibroblast growth factor receptor (FGFR) gene and its clinical manifestations in patients, particularly those in atypical cases.

METHODS

Twenty patients with craniosynostoses unrelated to Apert syndrome were enrolled in this study. The phenotypes indicated the following syndromes: 12 patients with unrelated Crouzon syndrome, including nine sporadic and three familial cases; two with sporadic Pfeiffer syndrome; and one with Antley-Bixler syndrome. The Crouzon phenotype was subdivided into three clinical forms: regular, top, and bottom ones. Two patients who demonstrated craniofacial anomalies and bilateral elbow joint contractures were categorized as having an unspecified craniosynostosis. Three cases of unclassifiable cloverleaf skull malformation were also analyzed. Fourteen mutations of the FGFR2 gene were identified in these patients; seven of the 10 cysteine-related mutations were substitutions of codon 342 in the third immunoglobulin-like domain of this gene. The phenotypes of these seven cases were three of regular Crouzon, two of unspecified craniosynostosis, and one each of top Crouzon and unclassifiable cloverleaf skull malformation. In addition, four of the seven patients were found to have the same genotype (Cys342Arg). The phenotypes of these patients, however, were quite variable, ranging from regular Crouzon to unclassifiable cloverleaf skull malformation.

CONCLUSIONS

The phenotypes of patients with craniosynostoses unrelated to Apert syndrome proved quite variable, even in cases in which patients demonstrated the same genotype. In view of the phenotypic diversity evident in cases in which the same mutation in the FGFR2 gene is present, it is possible that other disease-modifying genetic factors exist to control the abnormal gain-of-function that accompanies FGFR signaling.

Authors+Show Affiliations

Department of Neurosurgery, Yokohama City University Medical Center and Yokohama City University School of Medicine, Japan. sinito@mars.dti.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16206730

Citation

Ito, Susumu, et al. "Phenotypic Diversity in Patients With Craniosynostoses Unrelated to Apert Syndrome: the Role of Fibroblast Growth Factor Receptor Gene Mutations." Journal of Neurosurgery, vol. 102, no. 1 Suppl, 2005, pp. 23-30.
Ito S, Sekido K, Kanno H, et al. Phenotypic diversity in patients with craniosynostoses unrelated to Apert syndrome: the role of fibroblast growth factor receptor gene mutations. J Neurosurg. 2005;102(1 Suppl):23-30.
Ito, S., Sekido, K., Kanno, H., Sato, H., Tanaka, M., Yamaguchi, K., & Yamamoto, I. (2005). Phenotypic diversity in patients with craniosynostoses unrelated to Apert syndrome: the role of fibroblast growth factor receptor gene mutations. Journal of Neurosurgery, 102(1 Suppl), 23-30.
Ito S, et al. Phenotypic Diversity in Patients With Craniosynostoses Unrelated to Apert Syndrome: the Role of Fibroblast Growth Factor Receptor Gene Mutations. J Neurosurg. 2005;102(1 Suppl):23-30. PubMed PMID: 16206730.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenotypic diversity in patients with craniosynostoses unrelated to Apert syndrome: the role of fibroblast growth factor receptor gene mutations. AU - Ito,Susumu, AU - Sekido,Ken'ichi, AU - Kanno,Hiroshi, AU - Sato,Hironobu, AU - Tanaka,Masaaki, AU - Yamaguchi,Kazuo, AU - Yamamoto,Isao, PY - 2005/10/7/pubmed PY - 2005/10/20/medline PY - 2005/10/7/entrez SP - 23 EP - 30 JF - Journal of neurosurgery JO - J Neurosurg VL - 102 IS - 1 Suppl N2 - OBJECT: The goal of this study was to elucidate the genotype-phenotype relationship in syndromic craniosynostoses by analyzing the mutations of the fibroblast growth factor receptor (FGFR) gene and its clinical manifestations in patients, particularly those in atypical cases. METHODS: Twenty patients with craniosynostoses unrelated to Apert syndrome were enrolled in this study. The phenotypes indicated the following syndromes: 12 patients with unrelated Crouzon syndrome, including nine sporadic and three familial cases; two with sporadic Pfeiffer syndrome; and one with Antley-Bixler syndrome. The Crouzon phenotype was subdivided into three clinical forms: regular, top, and bottom ones. Two patients who demonstrated craniofacial anomalies and bilateral elbow joint contractures were categorized as having an unspecified craniosynostosis. Three cases of unclassifiable cloverleaf skull malformation were also analyzed. Fourteen mutations of the FGFR2 gene were identified in these patients; seven of the 10 cysteine-related mutations were substitutions of codon 342 in the third immunoglobulin-like domain of this gene. The phenotypes of these seven cases were three of regular Crouzon, two of unspecified craniosynostosis, and one each of top Crouzon and unclassifiable cloverleaf skull malformation. In addition, four of the seven patients were found to have the same genotype (Cys342Arg). The phenotypes of these patients, however, were quite variable, ranging from regular Crouzon to unclassifiable cloverleaf skull malformation. CONCLUSIONS: The phenotypes of patients with craniosynostoses unrelated to Apert syndrome proved quite variable, even in cases in which patients demonstrated the same genotype. In view of the phenotypic diversity evident in cases in which the same mutation in the FGFR2 gene is present, it is possible that other disease-modifying genetic factors exist to control the abnormal gain-of-function that accompanies FGFR signaling. SN - 0022-3085 UR - https://www.unboundmedicine.com/medline/citation/16206730/Phenotypic_diversity_in_patients_with_craniosynostoses_unrelated_to_Apert_syndrome:_the_role_of_fibroblast_growth_factor_receptor_gene_mutations_ L2 - https://thejns.org/doi/10.3171/ped.2005.102.1.0023 DB - PRIME DP - Unbound Medicine ER -