Malformations of cortical development: Fetal imaging and genetics

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. The detection rate of copy number variants and single‐nucleotide variants (SNVs) is as high as 68.8% in fetuses with malformations of cortical development. Lissencephaly or pachygyria were the most common phenotypic manifestations. ASPM pathogenic mutations were the most common SNVs in fetus with lissencephaly or pachygyria.