ASXL3-related disorder: Molecular phenotyping and comprehensive review providing insights into disease mechanism

Clin Genet. 2024 May;105(5):470-487. doi: 10.1111/cge.14506. Epub 2024 Feb 29.

Abstract

ASXL3-related disorder, sometimes referred to as Bainbridge-Ropers syndrome, was first identified as a distinct neurodevelopmental disorder by Bainbridge et al. in 2013. Since then, there have been a number of case series and single case reports published worldwide. A comprehensive review of the literature was carried out. Abstracts were screened, relevant literature was analysed, and descriptions of common phenotypic features were quantified. ASXL3 variants were collated and categorised. Common phenotypic features comprised global developmental delay or intellectual disability (97%), feeding problems (76%), hypotonia (88%) and characteristic facial features (93%). The majority of genetic variants were de novo truncating variants in exon 11 or 12 of the ASXL3 gene. Several gaps in our knowledge of this disorder were identified, namely, underlying pathophysiology and disease mechanism, disease contribution of missense variants, relevance of variant location, prevalence and penetrance data. Clinical information is currently limited by patient numbers and lack of longitudinal data, which this review aims to address.

Keywords: ASXL3; Bainbridge‐Ropers syndrome; Drosophila melanogaster; neurodevelopmental disorder.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple*
  • Child
  • Developmental Disabilities* / genetics
  • Facies*
  • Humans
  • Intellectual Disability* / genetics
  • Neurodevelopmental Disorders*
  • Phenotype
  • Repressor Proteins / genetics
  • Syndrome
  • Transcription Factors / genetics

Substances

  • Bainbridge-Ropers syndrome
  • Transcription Factors
  • ASXL3 protein, human
  • Repressor Proteins