Prenatal diagnosis and genetic study of 22q11.2 microduplication in Chinese fetuses: A series of 31 cases and literature review

Abstract

Background: Patients with 22q11.2 microduplication syndrome exhibit a high degree of phenotypic heterogeneity and incomplete penetrance, making prenatal diagnosis challenging due to phenotypic variability. This report aims to raise awareness among prenatal diagnostic practitioners regarding the variant's complexity, providing a basis for prenatal genetic counseling.

Methods: Family and clinical data of 31 fetuses with 22q11.2 microduplications confirmed by chromosomal microarray between June 2017 and June 2023 were considered.

Results: Primary prenatal ultrasound features of affected fetuses include variable cardiac and cardiovascular anomalies, increased nuchal translucency (≥3 mm), renal abnormalities, and polyhydramnios. More than half of fetuses considered showed no intrauterine manifestations; therefore, prenatal diagnostic indicators were primarily advanced maternal age or high-risk Down syndrome screening. Most fetuses had microduplications in proximal or central 22q11.2 regions, with only three cases with distal microduplications. Among parents of fetuses considered, 87% (27/31) continued the pregnancy. During follow-up, 19 cases remained clinically asymptomatic.

Conclusion: Nonspecific 22q11.2 microduplication features in fetuses and its mild postnatal disease presentation highlight the need to cautiously approach prenatal diagnosis and pregnancy decision-making. Increased clinical efforts should be made regarding providing parents with specialized genetic counseling, long-term follow-up, and fetal risk information.

Keywords: 22q11.2 microduplication; chromosomal microarray analysis; prenatal diagnosis; rearrangement.

FIGURE 1

Localization and parental origin of the 22q chromosome duplication region in 31 fetal cases. A schematic representation of chromosome 22 (data derived from the UCSC Genome Browser 2009, GRCh37/hg19 assembly [http://www.genome.ucsc.edu]) is shown. The red box indicates the relevant region of the chromosome.

FIGURE 2

Combined data from this study and previously published cases. (a) A comparison of non‐ultrasound and ultrasound abnormalities is shown to improve prenatal diagnostic indications for 22q11.2 microduplication and a (b) proportional distribution of abnormal ultrasound features in 22q11.2 microduplication is shown.