Prenatal diagnosis and pregnancy outcome of fetuses with 15q11.2 BP1-BP2 microdeletion syndrome: a single-center retrospective study of 34 cases

BACKGROUND: To investigate the clinical phenotype, genetic counseling and pregnancy outcome of fetus with 15q11.2 BP1-BP2 microdeletion syndrome (Burnside-Butler syndrome, BBS), and to provide scientific prenatal diagnosis and genetic counseling for parents of BBS fetuses. METHODS: A single-center retrospective analysis method was used to analyze the data from September 2017 to April 2025. Data of 34 pregnant women with BBS fetuses who met the indications for prenatal diagnosis and underwent karyotype analysis of amniotic fluid, cord blood, and peripheral blood and single-nucleotide polymorphism array (SNP-array) for chromosomal copy number variations (CNVs) were collected. The CNVs detected were judged according to the American College of Medical Genetics and Genomics (ACMG) classification of genetic variants. RESULTS: A total of 34 BBS fetuses were detected in 9689 cases of SNP array, and the detection rate was 0.35% (34/9689). The median size of 15q11.2 microdeletion was 507.0 (490.6~512.3) kb. Among the 34 cases of BBS, the proportion of prenatal ultrasound abnormalities (55.6% vs. 52.0%), abnormal results of Down's syndrome screening or non-invasive prenatal testing (NIPT) screening, (44.4% vs. 20.0%) and advanced maternal age (≥ 35 years; 55.6% vs. 44.0%), were all higher in the pathogenic (P) group compared to the variant of uncertain significance (VUS) group. Among the 34 BBS fetuses, 25 were classified as having ACMG variants of unknown clinical significance and 9 were classified as pathogenic. Among the 9 cases of BBS, parental traceability test showed that 1 case was paternal origin, 3 cases were maternal origin and 5 cases were not verified. Among the 9 BBS cases in the P group, 5 cases were not verified. The parentage tracing test showed that the genetic inheritance from the maternal source was higher than that from the paternal source (33.3% vs. 11.1%). Among the 27 follow-up cases, the 88.89% (24/27) were inherited from parents, while de novo cases were relatively few 11.11% (3/27). CONCLUSION: The detection rate of BBS fetus in this study was 0.35%. The fetal manifestations of BBS are diverse, and SNP array is of great value in the detection of fetal chromosomal microdeletions including 15q11.2. Among the BBS cases, the majority were inherited from parents, while de novo cases were relatively few. Pregnancies involving BBS fetuses require adequate prenatal counseling. For women who choose to continue their pregnancies, increased supervision and extended postpartum monitoring are warranted.