Prenatal diagnosis of posterior fossa anomalies: Additional value of chromosomal microarray analysis in fetuses with cerebellar hypoplasia

Prenat Diagn. 2018 Jan;38(2):91-98. doi: 10.1002/pd.5190. Epub 2018 Jan 10.

Abstract

Objective: To elucidate the relationship between copy number variations (CNVs) detected by high-resolution chromosomal microarray analysis (CMA) and the type of prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH).

Methods: This study involved 77 pregnancies with PFAs who underwent CMA.

Results: Chromosomal aberrations including pathogenic CNVs and variants of unknown significance were detected in 31.2% (24/77) of all cases by CMA and in 18.5% (12/65) in fetuses with normal karyotypes. The high detection rate of clinically significant CNVs was evident in fetuses with cerebellar hypoplasia (54.6%, 6/11), vermis hypoplasia (33.3%, 1/3), and Dandy-Walker malformation (25.0%, 3/12). Compare with fetuses without other anomalies, cases with CH and additional malformations had the higher CMA detection rate (33.3% vs 88.9%). Three cases of isolated unilateral CH with intact vermis and normal CMA result had normal outcomes. The deletion of 5p15, 6q terminal deletion, and X chromosome aberrations were the most frequent genetic defects associated with cerebellar hypoplasia.

Conclusion: Among fetuses with PFA, those with cerebellar hypoplasia, vermis hypoplasia, or Dandy-Walker malformation are at the highest risk of clinically significant CNVs. Chromosomal microarray analysis revealed the most frequent chromosomal aberrations associated with CH.

MeSH terms

  • Cerebellar Vermis / abnormalities
  • Cerebellum / abnormalities*
  • Cerebellum / embryology
  • Chromosome Aberrations*
  • DNA Copy Number Variations / genetics
  • Dandy-Walker Syndrome / diagnosis
  • Dandy-Walker Syndrome / embryology
  • Dandy-Walker Syndrome / genetics
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Female
  • Humans
  • Karyotyping
  • Magnetic Resonance Imaging
  • Microarray Analysis
  • Nervous System Malformations / diagnosis*
  • Nervous System Malformations / embryology
  • Nervous System Malformations / genetics
  • Pregnancy
  • Prenatal Diagnosis / methods*

Supplementary concepts

  • Cerebellar Hypoplasia