CHIME Syndrome in a Child With Homozygous PIGL p.Leu167Pro Variant

CHIME syndrome is a variable condition characterized by ichthyosiform dermatosis, accompanied by intellectual disability, ocular colobomas, ear anomalies, and heart defects. It is an autosomal recessive condition caused by biallelic pathogenic variants in the PIGL gene. Until now, all reports of individuals affected with CHIME syndrome showed the PIGL c.500T>C p.Leu167Pro DNA variant on one allele of the PIGL gene, in combination with another PIGL DNA variant on the other allele. This has led to the hypothesis that the p.Leu167Pro variant determines to a mild phenotypic effect only and that the core phenotype is determined by the second PIGL DNA variant. We report the first individual with CHIME syndrome, a 6-year-old girl, with homozygous PIGL p.Leu167Pro variants, defusing this hypothesis as she is not mildly affected.