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Monogenic conditions and central nervous system anomalies: a prospective study, systematic review and meta-analysis
Baptiste, Caitlin D Jacob, Preethi A
Baptiste, Caitlin D
Jacob, Preethi A
Abstract
Objectives
Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities.
Methods
Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model.
Results
Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%–36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%–34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%–23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%–40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%–57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus.
Conclusions
Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.
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Date
2024
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Article
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Blayney, G. V., Laffan, E., Jacob, P. A., Baptiste, C. D., Gabriel, H., Sparks, T. N., Yaron, Y., Norton, M. E., Diderich, K., Wang, Y., Chong, K., Chitayat, D., Saini, N., Aggarwal, S., Pauta, M., Borrell, A., Gilmore, K., Chandler, N. J., Allen, S., Vora, N., … Mone, F. (2024) Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis. Prenatal diagnosis v44(4) pp.422–431. https://doi.org/10.1002/pd.6466
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© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes. https://creativecommons.org/licenses/by-nc/4.0/