Krakow Deborah, Cohn Daniel H, Wilcox William R, Noh Grace J, Raffel Leslie J, Sarukhanov Anna, Ivanova Margarita H, Danielpour Moise, Grange Dorothy K, Elliott Alison M, Bernstein Jonathan A, Rimoin David L, Merrill Amy E, Lachman Ralph S
Department of Orthopaedic Surgery, University of California, Los Angeles, California.
Department of Human Genetics, University of California, Los Angeles, California.
Am J Med Genet A. 2016 Oct;170(10):2652-61. doi: 10.1002/ajmg.a.37772. Epub 2016 May 30.
Bent Bone Dysplasia-FGFR2 type is a relatively recently described bent bone phenotype with diagnostic clinical, radiographic, and molecular characteristics. Here we report on 11 individuals, including the original four patients plus seven new individuals with three longer-term survivors. The prenatal phenotype included stillbirth, bending of the femora, and a high incidence of polyhydramnios, prematurity, and perinatal death in three of 11 patients in the series. The survivors presented with characteristic radiographic findings that were observed among those with lethality, including bent bones, distinctive (moustache-shaped) small clavicles, angel-shaped metacarpals and phalanges, poor mineralization of the calvarium, and craniosynostosis. Craniofacial abnormalities, hirsutism, hepatic abnormalities, and genitourinary abnormalities were noted as well. Longer-term survivors all needed ventilator support. Heterozygosity for mutations in the gene that encodes Fibroblast Growth Factor Receptor 2 (FGFR2) was identified in the nine individuals with available DNA. Description of these patients expands the prenatal and postnatal findings of Bent Bone Dysplasia-FGFR2 type and adds to the phenotypic spectrum among all FGFR2 disorders. © 2016 Wiley Periodicals, Inc.
FGFR2型弯骨发育不良是一种相对较新描述的具有诊断性临床、影像学和分子特征的弯骨表型。我们在此报告11例患者,包括最初的4例患者以及7例新患者,其中有3例长期存活者。产前表型包括死产、股骨弯曲,以及该系列11例患者中有3例羊水过多、早产和围产期死亡的发生率较高。存活者表现出在致死性患者中观察到的特征性影像学表现,包括骨骼弯曲、独特的(胡须状)小锁骨、天使状掌骨和指骨、颅骨矿化不良以及颅缝早闭。还注意到颅面异常、多毛症、肝脏异常和泌尿生殖系统异常。长期存活者均需要呼吸机支持。在9例有可用DNA的个体中鉴定出编码成纤维细胞生长因子受体2(FGFR2)的基因突变杂合性。这些患者的描述扩展了FGFR2型弯骨发育不良的产前和产后发现,并增加了所有FGFR2疾病的表型谱。© 2016威利期刊公司