Prenatal diagnosis of Wolf-Hirschhorn syndrome characterized by severe fetal growth restriction in three fetuses / 中华围产医学杂志

ABSTRACT

Objective:To analyze the prenatal clinical characteristics and genetic etiology of Wolf-Hirschhorn syndrome manifested by severe fetal growth restriction (FGR).Methods:Clinical data of three pregnant women admitted to Changsha Hospital for Maternal and Child Health Care from 2018 to 2020 due to severe FGR with or without other malformations diagnosed by prenatal ultrasound were collected. Amniotic fluid samples obtained by ultrasound-guided amniocentesis were analyzed by conventional G-banding staining technique and single nucleotide polymorphism array (SNP array). Parental peripheral blood cells were collected for SNP array to verify the source of variation.Results:(1) The karyotypes of both case 1 and 2 were normal, while case 3 had an abnormal karyotype of 46,XN,der(4)(9pter→9p234p15.31→4qter). (2) SNP array indicated a 7.8 Mb microdeletion in 4p16.3p16.1 cytoband in case 1 and a 5.5 Mb microdeletion in 4p16.3p16.2 cytoband in case 2, which were both de novo copy number variations. Case 3 harbored a 19.88 Mb deletion in 4p16.3p15.31 and a 10.89 Mb duplication in 9p24.3p23. (3) All three fetuses were diagnosed as Wolf-Hirschhorn syndrome, and their parents chose to terminate the pregnancies after genetic counseling. Conclusions:Considering the possibility of genetic disease, invasive prenatal diagnosis is suggested when prenatal ultrasonography showed severe FGR, regardless of other malformations, to clarify the cause and guide genetic counseling.