Prenatal diagnosis of thanatophoric dysplasia

Thanatophoric dysplasia is an autosomal dominant congenital disorder associated with primary bone dysplasia. Thanatophoric dysplasia is caused by mutation of the gene that encodes fibroblast growth factor 3 (FGFR3).

Case report: The paper presents two clinical observations of thanatophoric dysplasia. In both cases, pregnant women were referred for invasive prenatal diagnosis which identified the normal male karyotype of the fetus.

In the first case, a number of markers of chromosomal abnormalities were detected in the first trimester using ultrasound. There were no markers allowing to suspect skeletal dysplasia. The ultrasound examination performed at 19–20 weeks’ gestation revealed multiple congenital malformations including shortening and bowing of the limbs. The boy who was born at 36–37 weeks’ gestation after surgical delivery had the following congenital malformations: shortening of limb bones, hypoplasia of the chest, anomalies of the ribs and spine, secondary hypoplasia of the lungs. The child died in the neonatal period.

In the second case, there were the following abnormalities of the musculoskeletal system in the fetus at 14–15 weeks’ gestation: shortening and deformation of the tubular bones of the arms and legs, hypoplasia of the chest, clover-shaped skull. The patient provided the consent for termination of pregnancy.

Pathogenic variants in the FGFR3 gene were identified during a subsequent study of DNA which was isolated from chorionic villi. In the first case, the c.1948 A>G variant was identified, while the c.742 C>T was revealed in the second one; both variants were previously described as pathogenic.

Conclusion: It is necessary to confirm the diagnosis of thanatophoric dysplasia using molecular genetic research methods and ultrasound assessment showing the signs of fetal skeletal pathology in order to clarify the medical indications for termination of pregnancy and to determine the prognosis for future offspring in the family.