Malformations of cortical development: Fetal imaging and genetics

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Malformations of cortical development (MCD) are congenital brain abnormalities causing epilepsy and cognitive impairment.
• Genetic factors are significant in MCD etiology, with no current cure.
• In-utero diagnosis of MCD is increasingly possible via fetal MRI and ultrasound.

Purpose of the Study:

• To evaluate the diagnostic yield of genetic testing in fetuses with MCD.
• To correlate neuroimaging findings with genetic variations.

Main Methods:

• Retrospective review of 32 fetal MCD cases diagnosed via ultrasound or MRI.
• Analysis included chromosome karyotyping, SNP array/CNV sequencing, and whole-exome sequencing (WES).

Main Results:

• Genetic testing identified pathogenic copy number variants (CNVs) or single-nucleotide variants (SNVs) in 68.8% (22/32) of fetuses.
• Specifically, 3 pathogenic CNVs (9.4%) and 19 SNVs (59.4%) were detected.

Conclusions:

• Genetic testing, especially WES, is recommended for fetal MCD diagnosis.
• This facilitates outcome evaluation, prognosis assessment, and recurrence risk prediction for subsequent pregnancies.