Abstract / Summary
ABSTRACT Background Variants in STAR , encoding Steroidogenic Acute Regulatory (StAR) protein, and CYP11A1 , encoding the cholesterol Side‐Chain Cleavage (SCC) enzyme, result in proximal steroidogenic defects. These are classically described as presenting with neonatal‐onset primary adrenal insufficiency, with the additional finding of sex reversal in 46,XY newborns. However, the phenotypic spectrum is much wider. The present study aimed at describing the phenotypic heterogeneity and genotypes of patients with STAR and CYP11A1 variants followed up at a tertiary care centre in India. Methods Hospital records of all patients with variants in STAR and CYP11A1 who were followed up at the Paediatric Endocrinology division of a tertiary care hospital between January 2018 and January 2026 were reviewed for clinical details and genotypes. Results Variants in STAR and CYP11A1 were identified in four patients each. Among patients with variants in STAR , two had homozygous pathogenic/likely pathogenic variants, while two had two heterozygous variants; phase undetermined [of which one was a variant of uncertain significance (VUS)]. The presenting features were salt‐wasting crisis ( n = 3, at ages 2 years, 5 years and Day 15, respectively) and atypical genitalia ( n = 1). Among patients with variants in CYP11A1 , one had two heterozygous variants; phase undetermined (of which one was a VUS), while three had homozygous VUSs. The presentation ranged from adrenal crisis ( n = 1, at 3.8 years) and salt‐wasting crisis ( n = 1, at 10 months) to progressive hyperpigmentation ( n = 2, at ages 6.5 years and 21.9 years, respectively). None of the patients had genital ambiguity, while one patient presented with 46,XY sex reversal. Conclusion The present study highlights the wide phenotypic spectrum associated with STAR and CYP11A1 variants, ranging from classical neonatal salt‐wasting crisis with 46,XY sex reversal, to isolated primary adrenal insufficiency, or isolated undervirilisation, with later emergence of gluco‐ and mineralocorticoid deficiency.