Prenatal diagnosis and molecular cytogenetic characterization of 12 cases of chromosome 8 inverted duplication deletion syndrome.

Background: Inverted duplication of the short arm of chromosome 8 (inv dup del (8p)) and the deletion of its adjacent terminal represent a rare chromosomal rearrangement. To date, only a limited number of prenatal cases have been documented from a molecular cytogenetic perspective. This study investigates the molecular genetic characteristics and intrauterine ultrasound phenotypes of fetuses prenatally diagnosed with inv dup del (8p).

Methods: We retrospectively analyzed chromosomal microarray analysis (CMA) results from cases seeking prenatal diagnosis at the Medical Genetics Center of Guangdong Women and Children’s Hospital from January 2016 to December 2022. We identified 12 prenatal cases of inv dup del (8p) and summarized their prenatal clinical manifestations and associated genes by combining ultrasound findings with literature review.

Results: Both G-banding and CMA techniques confirmed the presence of interstitial duplication with concomitant terminal deletion of chromosome 8’s short arm in all 12 cases. The locations and lengths of the 8p duplications varied in their proximal breakpoint. Observed ultrasound findings included fetal increased nuchal translucency (NT), lateral cerebral ventricular dilatation, craniofacial dysmorphisms and abnormalities of the brain, heart and kidneys. Ectopic recombination appears to be the dominant mechanism for rearrangement formation in cases 1–11. In contrast, case 12 exhibited inv dup del (8p) without an intact region between duplication and deletion, which is better explained by the U-type exchange mechanism.

Conclusion: The intrauterine phenotypes of inv dup del (8p) are diverse, with cerebral and cardiac anomalies being the most commonly observed ultrasound findings. However, these clinical manifestations are not specific to inv dup del (8p), and some fetuses may not exhibit noticeable ultrasound abnormalities during early gestation. Therefore, definitive diagnostic testing through karyotyping and CMA is essential. Additionally, CMA enables precise detection of copy number variations (CNVs), including exact size and genomic location. This detailed information is critical for accurate genetic counselling and helps clarify the mechanism behind the inv dup (8p) rearrangement.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13023-025-03969-w.