The Glucocorticoid Resistance Syndrome: Two Cases of a Novel Pathogenic Variant in the Glucocorticoid Receptor Gene

Glucocorticoid resistance syndrome is a rare genetic disorder marked by insensitivity to glucocorticoids, leading to hyperactivation of the hypothalamic-pituitary-adrenal axis and potential excess of mineralocorticoids and/or androgens. This condition is linked to pathogenic variants in the NR3C1 gene, which encodes the glucocorticoid receptor. The study reports two cases—a mother and her son—exhibiting a mild hyperandrogenic phenotype due to a novel NR3C1 gene variant predicting a truncated protein. This variant contributes to glucocorticoid resistance syndrome, adding to the 33 known pathogenic variants, but no clear genotype-phenotype correlation has been established.