Background Prenatal invasive genetic testing is commonly recommended to pregnancies of early-onset FGR or FGR combined with a structural defect. Our study aimed to explore the genetic findings for FGR without structural malformations according to cytogenetic karyotyping and single nucleotide polymorphism array (SNP array) technology over a 10-year period. Methods A total of 488 pregnancies diagnosed with FGR without structural malformation were retrospectively reviewed. Cytogenetic karyotyping was performed on all the subjects, and SNP array was available from 272 of them. Based on the gestational age at onset, the cohort was classified into four groups: ≤ 24, 25–28, 29–32, and > 32 weeks of gestation. According to the ultrasound findings, they were grouped into isolated FGR, FGR with soft markers, and FGR with non-structural anomalies. In pregnancies of young maternal age, based on the results of maternal serum screening (MSS), they were categorized into high-risk and low-risk MSS groups. Results Nineteen (3.9%) cases of chromosomal abnormalities were detected by cytogenetic karyotyping, including 11 cases of numerical abnormalities, 5 cases of structural abnormalities, and 3 cases of mosaicism. Trisomy 21 was the most frequent abnormality. Abnormal karyotypes were more frequently observed in cases diagnosed at ≤ 24 weeks (7.2%) than those in any other group. Among pregnancies with normal karyotype, an incremental yield of 4.2% were revealed by SNP array technology regarding clinically relevant aberrations. The additional detection rates by SNP array in cases diagnosed at ≤ 24 weeks (6.5%), cases with soft markers (9.5%), and cases with high-risk MSS (12.0%) were higher than those in other groups within each classification. All the cases with abnormal karyotypes and 7 out of 11 pregnancies with clinically relevant anomalies revealed by SNP array alone resulted in pregnancy terminations. Conclusion Chromosome abnormality is an important etiology for FGR with no associated structural malformations, and plays a crucial role in pregnancies decision-making. SNP array improves the detection of genetic anomalies especially in FGR diagnosed at ≤ 24 weeks, FGR combined with soft makers, and FGR combined with high-risk MSS.

Objective This study aimed to examine the effectiveness of the SNP array for the prenatal diagnosis of congenital heart disease (CHD) screened by echocardiography. Patients and Methods A total of 356 pregnant women with fetal congenital heart malformations revealed by echocardiography at the Center for Prenatal Diagnosis of Fujian Maternal and Children Hospital during the period from November 2016 through July 2019 were recruited. The fetuses were assigned into three cohorts, including 142 with a single cardiac malformation, 106 with multiple cardiac malformations and 108 with cardiac and extracardiac malformations. All fetuses underwent chromosomal karyotyping and SNP array simultaneously, and the effectiveness of the SNP array for the prenatal diagnosis of CHD was evaluated. Results The overall prevalence of abnormal karyotypes was 9.3% among the 356 fetuses with CHD, and a higher proportion was found in fetuses with cardiac and extracardiac malformations (18.5%) than in those with single (5.6%) or multiple cardiac malformations (4.7%) ( P <0.05). Consistent with karyotype analysis, SNP array detected an additional 25 fetuses with pathogenic copy number variations (CNVs), seven with variant of unknown significance (VOUS) and seven with benign CNVs, and a lower proportion of abnormal CNV was found in fetuses with a single cardiac malformation (4.2%) than in those with multiple cardiac malformations (9.4%) or cardiac and extracardiac malformations (14.8%) ( P <0.05). Among the 33 fetuses with chromosomal abnormality, postnatal follow-up showed termination of pregnancy in 25 with pathogenic CNVs, one with VOUS, and six with normal karyotypes and SNP array findings but severe multiple malformations by ultrasonography. Conclusion SNP array increases the overall detection of abnormal CNVs by 9%, which improves the detection of CNVs associated with CHD. SNP array may serve as a tool for prenatal diagnosis of CHD that facilitates the discovery of pathogenic genes associated with CHD and provide valuable insights into the precision assessment of fetal prognosis during the prenatal counseling.

Pallister‐Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV‐seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.

Objectives 16p13.11 microdeletion/microduplication are rare genetic diseases with incomplete penetrance, most of which have been reported in adults and children, with ultrasound phenotyping in fetuses rarely described. Here, we have analyzed prenatal ultrasound phenotypic characteristics associated with 16p13.11 microdeletion/microduplication, in order to improve the understanding, diagnosis and monitoring of this disease in the fetus. Methods A total of 9000 pregnant women who underwent invasive prenatal diagnosis for karyotyping and SNP-array were retrospectively analyzed in tertiary referral institutions from October 2016 to January 2022. Results SNP-array revealed that 20 fetuses had copy number variation (CNV) in the 16p13.11 region, out of which 5 had 16p13.11 microdeletion and the rest showed microduplication, along with different ultrasound phenotypes. Furthermore, 4/20 cases demonstrated structural abnormalities, while the remaining 16 cases were atypical in ultrasound. Taken together, 16p13.1 microdeletion was closely related to thickened nuchal translucency, while 16p13.11 microduplication was more closely associated with echogenic bowel. Only 5/15 fetuses were verified by pedigree, with one case of 16p13.11 microdeletion being de novo, and the other cases of 16p13.11 microduplication were inherited from one parent. In 4/20 cases, the pregnancy was terminated. Except for one case with short stature and another one who underwent lung cystadenoma surgery, no abnormalities were reported in the other cases during follow-up. Conclusion Fetuses with 16p13.11 microdeletion/microduplication had no characteristic phenotype of intrauterine ultrasound and was in good health after birth, thus providing a reference for the perinatal management of such cases.

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