Diagnostic Utility of Genome and Transcriptome Sequencing in Identifying PIGL Variants Associated with Atypical CHIME Syndrome

March 10, 2026

Background

  • CHIME syndrome is a rare autosomal recessive disorder of glycosylphosphatidylinositol (GPI) anchor biosynthesis caused by biallelic pathogenic variants in the PIGL gene.
  • Classic features include colobomas, congenital heart defects, ichthyosiform dermatosis, intellectual disability, and ear anomalies.
  • Additional features that are frequently reported include larger size at birth, renal/genitourinary anomalies, craniofacial dysmorphisms, short fingers, and elevated alkaline phosphatase levels.
  • Recent reports have described individuals with atypical presentations lacking some of the classic phenotypic features, suggesting broader clinical heterogeneity.