The Prenatal Diagnosis and Clinical Outcomes of Fetuses With 15q11.2 Copy Number Variants: A Case Series of 36 Patients.

Jessica Kang,Wen-Wei Hsu,Yi-Yun Tai,Yi-Ning Su,Chien-Hui Hung,Kuan-Ying Huang,Chi-Ling Chen,Chien-Nan Lee,Ming-Wei Lin,Shin-Yu Lin

doi:10.3389/fmed.2021.754521

Abstract

Prenatal genetic counseling of fetuses diagnosed with 15q11.2 copy number variants (CNVs) involving the BP1–BP2 region is difficult due to limited information and controversial opinion on prognosis. In total, we collected the data of 36 pregnant women who underwent prenatal microarray analysis from 2010 to 2017 and were assessed at National Taiwan University Hospital. Comparison of the maternal characteristics, prenatal ultrasound findings, and postnatal outcomes among the different cases involving the 15q11.2 BP1–BP2 region were presented. Out of the 36 fetuses diagnosed with CNVs involving the BP1–BP2 region, five were diagnosed with microduplications and 31 with microdeletions. Among the participants, 10 pregnant women received termination of pregnancy and 26 gave birth to healthy individuals (27 babies in total). The prognoses of 15q11.2 CNVs were controversial and recent studies have revealed its low pathogenicity. In our study, the prenatal abnormal ultrasound findings were recorded in 12 participants and were associated with 15q11.2 deletions. No obvious developmental delay or neurological disorders were detected in early childhood.

Highlights

Copy number variants (CNVs) involving chromosome 15q11-q13 is a challenging issue for prenatal counseling
Different microarray platforms were used in our study, the single nucleotide polymorphism (SNP) microarray analysis was used with the majority of our subjects
Total of 36 cases were diagnosed with 15q11.2 copy number variants (CNVs) involving the BP1–BP2 region

Summary

Introduction

Copy number variants (CNVs) involving chromosome 15q11-q13 is a challenging issue for prenatal counseling. The 15q11.2 CNV involving non-imprinting breakpoints 1–2 (BP1–BP2) is included in the category of incidental finding not to be reported due to no definite linkage to phenotype and low penetrance [2], and a recent study has concluded with low pathogenicity of this region [3]. It is interesting that the PWS/AS cases with type I deletion were presented with more severe neurodevelopmental disorders than the cases with type II deletion. This finding has indicated that BP1–BP2 region might affect the phenotypes in the patients with PWS/AS [11]. Various clinical manifestations have been detected in the cases with 15q11.2 CNVs, such as motor delay, intrauterine growth retardation, macrocephaly, non-specific dysmorphic features [1, 10], congenital cataracts, esophageal atresia [12], and arthrogryposis [13]

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Results

Conclusion