IMR Press / JMCM / Volume 3 / Issue 1 / DOI: 10.31083/j.jmcm.2020.01.001
Open Access Case Report
Prenatal diagnosis of fetal thanatophoric dysplasia type 1 with de novo c.2419T > G (p. Ter807Gly) (X807G) gene mutation in fibroblast growth factor receptor 3 (FGFR3) showing increased nuchal translucency at the first trimester of gestation: A case report with review of the literature
Show Less
1 Fifth Obstetrics and Gynecology Department, “Elena Venizelou” General Hospital, Athens 11521, Greece
2 Eurogenetical MSA, Thessaloniki 55133, Greece
3 Pharmacy Department, University of Patras, Patra 26504, Greece
4 Pharmacy Department, Frederick University, Nicosia 1036, Cyprus
5 Obstetrics and Gynecology Department, Great Western Hospital, Marlborough Road, Swindon, Wiltshire, SN3 6BB, UK
6 First Pathology Department, Medical School, National Kapodistrian University, Athens 11527, Greece
7 Sixth Obstetrics and Gynecology Department, “Elena Venizelou” General Hospital, Athens 11521, Greece
J. Mol. Clin. Med. 2020, 3(1), 19–28;
Published: 20 March 2020

Thanatophoric dysplasia (TD) is a rare form of lethal skeletal dysplasia with underdevelopment of skeleton and dwarfism. The femur is curved in subtype 1, and straight in subtype 2 TD. Other characteristics include a narrow chest, small ribs and hypoplastic lungs. TD is due to activating mutations in fibroblast growth factor receptor 3 (FGFR3), which result in increased receptor activation and alterations in the process of endochondral ossification in all long bones. The aim of the present study was to present the perinatal ultasonographic findings at the 1st and 2nd trimester of a pregnancy and the underlying molecular defect in a fetus with TD type 1, due to a rare mutation in the FGFR3 gene. Ultrasonography performed at the 12w2d of gestation showed increased nuchal translucency (NT). Prenatal karyotype was normal for the XX fetus. Ultrasonography at 17 weeks and 5 days of gestation revealed narrow thorax, abdominal protrusion and a decreased rate of development of the femur (Femur Length, FL < 5th percentile). Molecular genetic analysis to exclude possible overlapping syndromes was performed and revealed de novo c.2419T > G (p. Ter807Gly) (X807G) gene mutation in FGFR3. Fetal autopsy confirmed the prenatal prediction of lethality. We conclude that a fetus with a heterozygous c.2419T > G mutation in FGFR3, presented characteristic biometric parameters and ultrasonographic and autopsy findings consistent with the diagnosis of TD type 1. In addition, the combination of ultrasonography, molecular genetic analysis and autopsy is helpful for the appropriate genetic counselling and perinatal management.

skeletal dysplasia
prenatal diagnosis
molecular and genetic analysis
thanatophoric dysplasia
perinatal mortality
Figure 1.
Back to top