Whole Exome Sequencing Diagnoses the First Fetal Case of Bainbridge-Ropers Syndrome Presenting as Pontocerebellar Hypoplasia Type 1

Birth Defects Res. 2018 Apr 3;110(6):538-542. doi: 10.1002/bdr2.1191. Epub 2018 Jan 8.

Abstract

Background: Bainbridge-Ropers syndrome (BRPS) is a recently identified severe disorder characterized by failure to thrive, facial dysmorphism, and severe developmental delay, caused by de novo dominant loss of function mutation in the ASXL3 gene.

Case: We report here the first case of prenatal BRPS in a fetus presenting with arthrogryposis on ultrasound and for pontocerebellar hypoplasia type 1 (PCH1) following neuropathological examination. The diagnosis was done by whole exome sequencing that identified a novel de novo ASXL3 mutation. We review 29 previous published cases.

Discussion: The fetopathological examination allowed to extend the phenotype to central nervous system and the genetic study highlights ASXL3 as a dominant gene responsible for PCH1 phenotype. Recognizing heterozygous ASXL3 mutation as a cause of prenatal PCH1 is essential for both large scale molecular analysis in the NGS era and genetic counseling.

Keywords: ASXL3; Bainbridge-Ropers syndrome; arthrogryposis; fetal pathology; pontocerebellar hypoplasia type 1.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Diagnosis, Differential
  • Fetus / pathology*
  • Humans
  • Olivopontocerebellar Atrophies / diagnosis*
  • Olivopontocerebellar Atrophies / genetics*
  • Phenotype
  • Syndrome
  • Whole Exome Sequencing*

Supplementary concepts

  • Pontocerebellar Hypoplasia Type 1