Prenatal diagnosis of Miller–Dieker syndrome: Integrated application of ultrasound, MRI, and genetic analysis

To evaluate the diagnostic utility of ultrasound, magnetic resonance imaging (MRI), and Genetic Analysis in the prenatal identification of Miller–Dieker syndrome (MDS) to improve early detection and diagnostic accuracy. We conducted a retrospective analysis of four fetuses with MDS diagnosed via array comparative genomic hybridization (aCGH). The data included maternal demographics, prenatal ultrasound and MRI findings, aCGH results, and pregnancy outcomes. The four fetuses exhibited classic MDS–associated brain malformations on MRI, including lissencephaly/pachygyria. Prenatal ultrasound revealed lissencephaly/pachygyria and Sylvian fissure abnormalities in three cases, ventriculomegaly with polyhydramnios in two, fetal growth restriction in two, cavum septum pellucidum widening in one, bilateral ependymal cysts in one, and a minor omphalocele in one. Parental karyotyping confirmed de novo mutations in all cases. Pregnancy management included selective fetal reduction (n = 1) and termination (n = 3). aCGH revealed deletions (1.7–4.77 Mb) spanning the MDS–critical region (17p13.3), with all cases involving PAFAH1B1 haploinsufficiency. Notably, larger deletions were correlated with more severe neuroimaging abnormalities. Combining prenatal ultrasound with MRI effectively revealed MDS–related structural brain anomalies, while aCGH precisely delineated 17p13.3 deletions. This multimodal approach significantly enhances diagnostic accuracy, facilitating early intervention and informed genetic counseling.