Genetic tests aid in counseling of fetuses with cerebellar vermis defects

Prenat Diagn. 2020 Sep;40(10):1228-1238. doi: 10.1002/pd.5732. Epub 2020 May 28.


Objective: To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD).

Methods: From 2013 to 2019, we performed CMA on 43 fetuses with CVD, who were divided into cerebellar vermis hypoplasia (CVH) group and Dandy-Walker malformation (DWM) group according to morphological subtypes. Subsequently, WES was performed on 19 fetuses with normal CMA results to identify diagnostic genetic variants (DGVs).

Results: Chromosome aneuploidies and clinically significant copy number variants were identified in 23.3% (10/43) of fetuses, and a significantly higher positive rate was found in fetuses with multiple compared with isolated malformations (36% vs 5.6%, P = .028). STAG2 genes related to Xq25 duplication syndrome was possibly a novel candidate gene for CVD. WES detected eight DGVs in seven genes among the 19 fetuses tested. Autosomal recessive ciliopathies (4/8) caused by TMEM231, CSPP1, and CEP290 mutations, were the most frequent monogenetic diseases, followed by Opitz GBBB syndrome (2/8) caused by MID1 and SPECC1L variants.

Conclusion: The combined use of CMA and WES has the potential to provide genetic diagnoses in 42% (18/43) of fetal CVD. WES should be offered when CMA results are normal.

MeSH terms

  • Adult
  • Aneuploidy
  • Cerebellar Vermis / abnormalities*
  • Cerebellar Vermis / diagnostic imaging
  • China
  • Chromosome Aberrations / embryology
  • Exome Sequencing / methods
  • Female
  • Fetus / abnormalities
  • Fetus / diagnostic imaging
  • Genetic Counseling* / methods
  • Genetic Testing* / methods
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Microarray Analysis / methods
  • Nervous System Malformations / diagnosis*
  • Nervous System Malformations / genetics
  • Pregnancy
  • Pregnancy Outcome
  • Prenatal Diagnosis* / methods
  • Retrospective Studies
  • Ultrasonography, Prenatal
  • Young Adult