Prenatal diagnosis and estimated penetrance of 15q11.2 BP1-BP2 microdeletion syndrome in a Chinese cohort: a retrospective study and literature review.

Abstract

Background: The 15q11.2 BP1-BP2 microdeletion (Burnside-Butler syndrome) is a recurrent copy number variation associated with variable neurodevelopmental outcomes. Its incomplete penetrance and broad phenotypic spectrum challenge prenatal genetic counseling. This study aimed to characterize prenatal and postnatal clinical outcomes associated with the 15q11.2 BP1-BP2 microdeletion and to provide evidence to inform prenatal genetic counseling.

Results: Among 5246 high-risk pregnancies undergoing invasive prenatal diagnosis at a single center between January 2022 and February 2026, 25 fetuses with 15q11.2 BP1-BP2 microdeletion were identified by chromosomal microarray analysis. Of these, 9 fetuses showed soft ultrasound markers, 3 had fetal growth restriction, and 3 had major structural anomalies. Five pregnancies were electively terminated, whereas 20 were continued. Postnatal follow-up ranging from 3 months to 3 years and 8 months revealed no developmental or growth abnormalities among live-born children (penetrance 0%). A literature review of prenatally diagnosed cases showed that 65 of 127 fetuses had abnormal prenatal ultrasound findings, while postnatal phenotypic abnormalities were reported in 12 of 77 live-born children. When the analysis was restricted to cases with standardized pediatric follow-up (n = 55), the penetrance decreased to 5.5%.

Conclusions: Our data indicate that 15q11.2 BP1-BP2 microdeletion generally has favorable early postnatal outcomes. Given the low penetrance observed in prenatally ascertained cohorts and the mild effect size of this copy number variation, our findings suggest that the clinical implications of routinely reporting isolated 15q11.2 BP1-BP2 microdeletion in the prenatal setting may need to be interpreted with caution. Longer-term follow-up studies remain necessary to further clarify the neurodevelopmental impact of this microdeletion.