Prenatal Diagnosis of Central Nervous System Anomalies by High-Resolution Chromosomal Microarray Analysis.

Lijuan Sun,Yuqing Ma,Yani Yan,Xin Wang,Juan Zhang,Ling Yao,Qingqing Wu,Li Wang,Shi-Wen Jiang,Yan Liu

doi:10.1155/2015/426379

Abstract

The aims of this study were to evaluate the contribution of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with central nervous system (CNS) anomalies but normal chromosomal karyotype. A total of 46 fetuses with CNS anomalies with or without other ultrasound anomalies but normal karyotypes were evaluated by array-based comparative genomic hybridisation (aCGH) or single-nucleotide polymorphism (SNP) array. The result showed that CNVs were detected in 17 (37.0%) fetuses. Of these, CNVs identified in 5 (5/46, 10.9%) fetuses were considered to be likely pathogenic, and CNVs detected in 3 (3/46, 6.5%) fetuses were defined as being of uncertain clinical significance. Fetuses with CNS malformations plus other ultrasound anomalies had a higher rate of pathogenic CNVs than those with isolated CNS anomalies (13.6% versus 8.3%), but there was no significant difference (Fisher's exact test, P > 0.05). Pathogenic CNVs were detected most frequently in fetuses with Dandy-Walker syndrome (2/6, 33.3%) when compared with other types of neural malformations, and holoprosencephaly (2/7, 28.6%) ranked the second. CMA is valuable in prenatal genetic diagnosis of fetuses with CNS anomalies. It should be considered as part of prenatal diagnosis in fetuses with CNS malformations and normal karyotypes.

Highlights

The prevalence of central nervous system (CNS) abnormalities is 0.14–0.16% in live births and reaches as high as 3–6% in stillbirths [1]
Pathogenic CNVs were identified in 5 (10.9%) fetuses including 2 cases with isolated CNS malformations and 3 cases associated with other organ abnormalities
Information for 5 fetuses with pathogenic CNVs and 3 cases with CNVs of uncertain clinical significance was shown in Figures 1 and 2, and Table 2

Summary

Introduction

The prevalence of CNS abnormalities is 0.14–0.16% in live births and reaches as high as 3–6% in stillbirths [1]. CNS anomalies are a group of serious birth defects associated with high rates of infant death or disability. In addition to their threat to life, CNS malformations cause enormous direct and indirect health costs [2]. Studies have shown that CNS malformations detected by ultrasonography were strongly associated with chromosomal abnormalities, especially trisomy 13 and 18 [5, 6]. There remains a dilemma in prenatal diagnosis of fetuses who have CNS anomalies, either with or without other organ abnormalities, but have normal karyotypes

Objectives

Methods

Results

Conclusion