Prenatal diagnosis, ultrasound findings, pregnancy outcomes and follow-up information analysis of xp22.31 deletion /duplication syndrome

Objective Analyze the ultrasound features, single nucleotide polymorphism microarray (SNP-array) outcomes, pregnancy results, and follow-up data of fetuses with Xp22.31 deletion or duplication in mid to late pregnancy. Methods A retrospective analysis was carried out on 10 cases diagnosed with Xp22.31 deletion and 11 cases with duplication, identified through SNP-array testing. The analysis focused on assessing ultrasound abnormalities, tracing parental origins, pregnancy outcomes, and postnatal follow-up conditions. Results The deletion sizes in the 10 deletion cases ranged from 913 Kb to 1.81 Mb, while the duplication sizes in the 11 duplication cases ranged from 1.29 Mb to 2.35 Mb, encompassing nine OMIM genes including STS, ANOS1, DXS1283E, VCS3B, and HDHD1A. Among the fetuses with deletions, four cases (40.0%, 4/10) exhibited ultrasound abnormalities, which included cardiovascular system malformations, lateral ventriculomegaly, clubfoot, increased nuchal translucency, and polyhydramnios. Notably, Case 5 involved a fetus with complex multi-organ malformations, including bilateral ventriculomegaly, a ventricular septal defect, and clubfoot. Among the 11 cases of duplications, three cases (27.3%, 3/11) exhibited ultrasound abnormalities, primarily featuring cardiovascular malformations, ventriculomegaly, and polyhydramnios. Of the 10 deletion cases, eight underwent parental origin testing, with seven cases inherited (six maternal and one paternal) and one case of de novo mutation. Among the 11 duplication cases, eight underwent parental origin testing, with seven cases being inherited (four maternal and three paternal) and one case representing a de novo mutation. Of the 10 deletion cases, six chose to terminate the pregnancy, while four decided to continue. Follow-up revealed that Case 6 was diagnosed with STS ichthyosis after birth, and the sbling of Case 3 and Case 10 exhibited delayed walking and speech development. In the duplication group, one case opted for termination of pregnancy, while 10 continued with their pregnancies. Follow-up identified that Case 18 exhibited delayed walking and speech development. Conclusion This study provides a preliminary assessment of the genotypes and phenotypes of fetuses with Xp22.31 deletion /duplication, expanding the phenotypic spectrum of Xp22.31 deletion /duplication syndrome. The findings indicate that prenatal Xp22.31 deletion in male fetuses are likely to manifest as STS ichthyosis after birth. Xp22.31 deletion and duplication may be associated with cardiovascular malformations. For fetuses with Xp22.31 deletion /duplication that appear phenotypically normal prenatally, postnatal monitoring of their neurological development is crucial.