Thanatophoric Dysplasia: Literature Review and Clinical Case in Monochoric Diamniotic Twins

Abstract

Thanatophoric dysplasia, TD (OMIM: 187600, 87601) belongs to the group of FGFR3 chondrodysplasias and is divided intotypes I and II. The incidence of TD is approximately 1:20,000-50,000 newborns. TD is usually caused by pathogenic variantsin the FGFR3 gene, which provides instructions for making a protein involved in the development and maintenance of bone andbrain tissue. Mutations in the gene result in excessive protein activity. TD is inherited as an autosomal dominant trait, althoughcases of autosomal recessive inheritance have been described.According to the radiologic changes of the bones and skull, there are 2 clinical types of TD: type I (TD1, MIM 187600) andtype II (TD2, MIM 187601) with some overlap between them. Type I TD is characterized by micromelia with curved femurs,marked platyspondylia with or without a cloverleaf skull. TD type II is characterized by micromelia with straight femurs andthe uniform presence of moderate to severe craniosynostosis with a leaf-shaped skull deformity due to premature closure of the coronal and lambdoid sutures..The diagnosis of TD is made syndromologically and/or radiologically and/or by detection of a heterozygous pathogenicFGFR3 variant identifi ed by molecular genetic testing.The article presents a rare clinical case of TD in monochorionic dizygotic twins with a fatal outcome. During prenatalultrasound examination at 26-27 and 35-36 weeks of gestation, signs of skeletal dysplasia were diagnosed in both fetuses against the background of pronounced polyhydramnios. It should be noted that the father of the children is over 60 years old.The diagnosis of both children was made syndromologically and radiologically based on the detection of phenotypic signs of TD(predominance of the skull over the face, short upper and lower limbs, altered shape of the chest, infl amed nasal bridge) and radiological signs of TD (short ribs, narrow chest, relative macrocephaly, micromelia of all limbs). Genetic testing for TD was not performed.The clinical case was published with the consent of the parents in accordance with the principles of bioethics.