Steroidogenic acute regulatory protein (STAR) deficiency: Our experience and systematic review for phenotype–genotype correlation

Abstract Objective Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR . A systematic review of phenotype–genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype–genotype correlation. Design, Patients and Measurements Retrospective review of three genetically proven LCAH patients from our centre and per‐patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia). Results We report three new LCAH probands from India, all diagnosed post‐infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two‐thirds of LCAH probands were East‐Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A ( n = 55), B ( n = 9) and C ( n = 8). All nonsense and frameshift and most of the splice‐site variants and deletion/insertions were present in Group A. Conclusions We report three new cases of LCAH from India. We propose a phenotype‐derived genotypic classification of reported STAR variants in 46,XY LCAH.