16p13.11 deletion/duplication: a large cohort study on prenatal diagnosis, postnatal outcomes, and phenotypic...

To expand the clinical phenotype spectrum and improve the understanding of prenatal ultrasound manifestations and fetal prognosis of 16p13.11 deletion/duplication syndrome in the East Asian population.

We conducted a comprehensive ultrasound phenotypic analysis, pedigree analysis and long-term postnatal outcome follow-up on 201 fetuses with 16p13.11 deletion/duplication, as well as on the phenotypic manifestations of 14 patients who underwent chromosomal microarray analysis between April 2013 and July 2024. Descriptive statistical analysis was used.

The detection rates were 0.08% and 0.18%, the frequencies of de novo occurrence were 26.9% and 14.5%, and the rates of abnormal postnatal phenotypes were 25% and 17.5% in our prenatal cohort of deletion and duplication, respectively. Overall, 28.6% of deletions and 15.9% of duplications exhibited abnormal postnatal phenotypes even if they were inherited from a phenotypically normal parent. Developmental delay was the most common clinical abnormality. Immune disorders, torticollis, concealed penis and cryptorchidism were closely related phenotypes that had previously gone unnoticed. Copy number variations extending to intervals I + II or II + III appeared to be associated with a broader range of phenotypes. Isolated choroid plexus cysts may be the most relevant ultrasound soft marker for deletion, whereas isolated thickened nuchal translucency appears to be more closely associated with duplication. Cardiovascular and urinary malformations were the most frequently detected ultrasound structural abnormalities.

The large East Asian prenatal cohort is conducive to enhancing genetic counseling for 16p13.11 deletion/duplication syndrome by facilitating a more accurate prediction of fetal prognosis and developmental potential.