Incomplete trisomy 15 rescue associated with hypermethylation of the Prader–Willi critical region

Objectives To present a rare prenatal case of incomplete trisomy 15 rescue with hypermethylation in the Prader–Willi critical region and to emphasize the diagnostic challenges associated with discordant results among NIPT, chromosomal microarray, and karyotype, highlighting the critical role of methylation analysis in confirming the diagnosis. Case report Our patient of 41-yea-old underwent NIPT showed trisomy 15 but low risk in PWS and Angelman syndrome. Subsequent karyotyping and CGH array provided discordant results possibly due to incomplete trisomy rescue. To clarify the diagnosis, MLPA was performed to confirm the hypermethylation of the Prader–Willi critical region, presenting as atypical PWS. Conclusion This case highlights the importance of MLPA test in the diagnosis workflow of atypical PWS caused by incomplete trisomy rescue. Early recognizing of atypical PWS is important due to its variable prognosis reported by current literatures.