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. 2024 Apr;12(4):e2440.
doi: 10.1002/mgg3.2440.

Malformations of cortical development: Fetal imaging and genetics

Lin-Lin Wang  1   2 , Ping-Shan Pan  2 , Hui Ma  2 , Chun He  2 , Zai-Long Qin  2 , Wei He  2 , Jing Huang  2 , Shu-Yin Tan  2 , Da-Hua Meng  2 , Hong-Wei Wei  2 , Ai-Hua Yin  1   3
Affiliations

Malformations of cortical development: Fetal imaging and genetics

Lin-Lin Wang et al. Mol Genet Genomic Med. 2024 Apr.

Abstract

Background: Malformations of cortical development (MCD) are a group of congenital disorders characterized by structural abnormalities in the brain cortex. The clinical manifestations include refractory epilepsy, mental retardation, and cognitive impairment. Genetic factors play a key role in the etiology of MCD. Currently, there is no curative treatment for MCD. Phenotypes such as epilepsy and cerebral palsy cannot be observed in the fetus. Therefore, the diagnosis of MCD is typically based on fetal brain magnetic resonance imaging (MRI), ultrasound, or genetic testing. The recent advances in neuroimaging have enabled the in-utero diagnosis of MCD using fetal ultrasound or MRI.

Methods: The present study retrospectively reviewed 32 cases of fetal MCD diagnosed by ultrasound or MRI. Then, the chromosome karyotype analysis, single nucleotide polymorphism array or copy number variation sequencing, and whole-exome sequencing (WES) findings were presented.

Results: Pathogenic copy number variants (CNVs) or single-nucleotide variants (SNVs) were detected in 22 fetuses (three pathogenic CNVs [9.4%, 3/32] and 19 SNVs [59.4%, 19/32]), corresponding to a total detection rate of 68.8% (22/32).

Conclusion: The results suggest that genetic testing, especially WES, should be performed for fetal MCD, in order to evaluate the outcomes and prognosis, and predict the risk of recurrence in future pregnancies.

Keywords: fetal imaging; genetics; malformations of cortical development; whole‐exome sequencing.

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Conflict of interest statement

All authors declare no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Figures

FIGURE 1
FIGURE 1
Study profile: +, pathogenic finding, −, normal result; N, number; TOP, termination of pregnancy.
FIGURE 2
FIGURE 2
Case no. 3: Hemimegalencephaly (HME). (A) MRI image of the brain, the arrow indicates the HME‐affected hemisphere. (B) Ultrasound image of the fetal head, the arrow indicates the hyperplasia cavum septum pellucidum. (C) Brain autopsy: gross morphology of the brain. (D) Histological examination: (a) HME‐affected hemisphere; (b) non‐HME‐affected hemisphere (Hematoxylin and eosin staining). (E) Whole‐exome sequencing results: mTOR p.Ser2215Phe. (a) father; (b) mother; (c) HME‐affected brain tissue; (d) non‐HME‐affected brain tissue.
See this image and copyright information in PMC

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