Prevalence of pathogenic copy number variants (CNVs) for specific ultrasound detected structural abnormalities using prenatal chromosomal microarray (CMA) in a multi-center cohort. T. Leung1, O. Chan1, SW. Cheung2, Y. Kwok1, KW. Choy1 1) Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong, Hong Kong; 2) Department of Molecular and Human Genetics, Baylor College of Medicine.

   A multi-center study of 491 pregnancies with structural ultrasound abnormalities using prenatal CMA (customized 44K Fetal Chip V1.0) was conducted to determine the prevalence of pathogenic CNVs. Pregnancies with isolated abnormality were categorized into the specific system. Pregnancies with abnormality in more than one system were grouped under multiple abnormalities. Fetuses with abnormalities of soft markers only were not included in this cohort. The prevalence of pathogenic CNVs was analyzed for each category. Results: The overall prevalence of pathogenic CNVs in pregnancies with structural ultrasound abnormalities was 11.8%. Abnormal CNVs were identified in 30.9% cases with multiple anomalies, 11.5% cases with isolated CNS anomalies, 6.9% cases with isolated CVS anomalies and 11.5% cases with isolated intrauterine growth retardation (IUGR). Pathogenic CNVs were not identified among pregnancies with isolated facial, gastrointestinal or respiratory anomalies. CMA testing was supplemented by karyotype in 84.6% of pregnancies. Among pregnancies with a normal karyotype, abnormal CNVs were identified in 17.5% cases with multiple anomalies, 3.7% cases with isolated skeletal anomalies, 2.1% cases with isolated CNS anomalies, 2% cases with isolated CNS anomalies and 11.1% cases with isolated IUGR,. CMA did not detect any abnormal CNVs for pregnancies that had a normal karyotype and affected by other isolated structural abnormalities including facial, gastrointestinal, respiratory and urogenital system. Conclusion: Pathogenic CNVs were identified in 17.5% pregnancies with multiple structural abnormalities that had a normal karyotype. Pregnancies with isolated structural anomaly were only associated with 0-3.7% risk of pathogenic CNVs after a normal karyotype. Prenatal CMA should be recommended as first tier testing for pregnancies with multiple structural abnormalities. However, the additional benefit of CMA in pregnancies with isolated anomaly was questionable.

You may contact the first author (during and after the meeting) at