16p13.11 microdeletion/microduplication in fetuses: investigation of associated ultrasound phenotypes, genetic anomalies, and pregnancy outcome follow-up

Abstract

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.

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age

“…CNVs have been detected in pregnant women with fetal USMs, suggesting that more attention should be paid to CNVs in pregnant women with fetal USMs, especially P CNVs [8, 13,[23][24][25][26]. In our study cohort, CNVs were more common than aneuploidies.…”

“…Copy number analysis is a well-known rst-tier approach for the prenatal diagnosis of fetuses with structural anomalies [11] and has also recently been used for the genetic etiological diagnoses of fetuses with USM. Previous studies have suggested an association between pathogenic (P) copy-number variants (CNVs) and second-trimester USM, such as EIF and echogenic bowel associated with 16p13.11 recurrent microdeletion, mild ventriculomegaly and CPCs associated with 1q21.1 recurrent microduplication, echogenic bowel associated with the 17q12 recurrent region, and ARSA associated with 22q11.2 deletions [8, 12,13]. Chromosomal microarray (CMA) and next-generation sequencing-based CNV analysis (CNV-seq) are used to detect CNVs in fetuses with USMs via invasive prenatal diagnosis.…”

Defining the scope of extended NIPS in Western China: evidence from a large cohort of fetuses with normal ultrasound scans

“…The clinical phenotype of 16p13.11 recurrent microduplication varies greatly, which can be manifested as autism spectrum disorder, learning difculties, brain MRI abnormalities, heart malformation and other abnormalities. The penetrance was approximately 7–8%, and about 80% of the cases are inherited from the father or mother with normal phenotype [ 33 – 35 ]. Therefore, this poses challenges for prenatal counseling because the associated neurodevelopmental phenotypes cannot be ascertained prenatally and it is difficult to quantify the risk to the fetus.…”