Clinical characteristics and genetic analysis of different Dandy-Walker malformation

Dandy-Walker malformation (DWM) is a rare congenital malformation of the central nervous system (CNS). It is characterized by variable hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, with or without an enlarged cisterna magna. Given that large-sample genetic analysis of DWM has not been conducted to date, this study aims to provide more comprehensive genetic counseling for prenatal diagnosis by summarizing the clinical features and genetic findings of DWM.

Between January 2010 and May 2025, among 22,048 pregnant women, there were 487 cases of fetal DWM that underwent prenatal diagnosis. Karyotyping, copy number variation sequencing (CNV-seq), single-nucleotide polymorphism array (SNP-array) or whole-exome sequencing (WES) were employed for prenatal genetic diagnosis. The results of ultrasonography, genetic analyses, and prognoses were tabulated.

Among the 487 cases, 35 (7.19%) were diagnosed with classic Dandy-Walker malformation (cDWM), 59 (12.11%) with vermian hypoplasia (VH), and 393 (80.70%) with mega cisterna magna (MCM) according to ultrasonography. A total of 245 cases (50.31%) presented with additional ultrasound abnormalities; central nervous system (CNS) abnormalities were the most prevalent (21.36%), among which ventriculomegaly constituted the primary finding. Prenatal genetic abnormalities were detected in 50 cases (10.27%). Karyotyping identified chromosomal abnormalities in 42 cases (8.62%), including numerical abnormalities, structural abnormalities, and chromosomal mosaicism, with trisomy-18 (2.26%) being the most commonly detected. There were 8 cases with normal karyotypes, but among them, 6 cases were detected with chromosomal abnormalities by CNV-seq/SNP-array, and 2 cases were detected with gene mutations by WES. Advanced maternal age was associated with an increased risk of chromosomal abnormalities, a proportion of which may present with DWM. Among the 453 cases that underwent follow-up, the cDWM and VH groups exhibited a significantly higher incidence of pregnancy terminations compared to the MCM group. Subsequent follow-up of cases with continued pregnancies revealed 1 case of neonatal death in the VH group and 5 cases in the MCM group. Additionally, there was 1 case of abnormal postnatal development in the cDWM group and 3 cases in the MCM group.

Pregnant women carrying DWM fetuses should undergo prenatal diagnosis including karyotyping, CNV-seq/SNP-array and WES if necessary, especially for fetuses with cDWM or VH, as the fetuses with cDWM or VH showed higher rates of genetic abnormalities. The pregnancy outcomes of most fetuses with MCM are favorable, while fetuses with cDWM or VH are prone to adverse gestational outcomes.