title: FGFR3 related skeletal dysplasias diagnosed prenatally by ultrasonography and molecular analysis: presentation of 17 cases.
abstract: Fibroblast Growth Factor Receptor 3 (FGFR3) related skeletal dysplasias are caused by mutations in the FGFR3 gene that result in increased activation of the receptors causing alterations in the process of endochondral ossification in all long bones, and include achondroplasia, hypochondroplasia, thanatophoric dysplasia, and SADDAN. Reports of prenatal diagnosis of FGFR3 related skeletal dysplasias are not rare; however, the correlation between 2nd trimester ultrasonographic findings and underlying molecular defect in these cases is relatively poor. There is a need for specific ultrasound (U/S) predictors than can distinguish lethal from non-lethal cases and aid an earlier prenatal diagnosis. Here we present one familial and 16 sporadic cases with FGFR3 related skeletal dysplasia, and we evaluate biometric parameters and U/S findings consistent with the diagnosis of skeletal dysplasia. U/S scan performed even at the 18th week of gestation can indicate a decreased rate of development of the femora (femur length (FL) <5th centile), while the mean gestational age at diagnosis is still around the 26th week. The utility of other biometric parameters and ratios is discussed (foot length, BPD, HC, FL/foot, and FL/AC). Prenatal cytogenetic and molecular genetic analyses were performed. A final diagnosis was reached by molecular analysis. In two cases of discontinued pregnancy, fetal autopsy led to a phenotypic diagnosis and confirmed the prenatal prediction of lethality. We conclude that the combination of U/S and molecular genetic approach is helpful for establishing an accurate diagnosis of FGFR3-related skeletal dysplasias in utero and subsequently for appropriate genetic counselling and perinatal management.
authors: Department of Genetics & Molecular Biology, "MITERA" General, Maternity & Children's Hospital, Athens, Greece. axatzaki@mitera.gr
authors: Angeliki
authors: A
authors: Hatzaki
authors: Stavros
authors: S
authors: Sifakis
authors: Despina
authors: D
authors: Apostolopoulou
authors: Dimitra
authors: D
authors: Bouzarelou
authors: Anastasia
authors: A
authors: Konstantinidou
authors: Dimitra
authors: D
authors: Kappou
authors: Apostolos
authors: A
authors: Sideris
authors: Emmanouil
authors: E
authors: Tzortzis
authors: Apostolos
authors: A
authors: Athanassiadis
authors: Lina
authors: L
authors: Florentin
authors: Perikles
authors: P
authors: Theodoropoulos
authors: Constantinos
authors: C
authors: Makatsoris
authors: Charalambos
authors: C
authors: Karadimas
authors: Voula
authors: V
authors: Velissariou
mesh_terms: D001848:Bone Diseases, Developmental / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D014463:Ultrasonography
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3