Primary Adrenal Insufficiency, Complete Sex Reversal, and Unique Clinical Phenotype in a Patient with Severe CYP11A1 (P450scc) Deficiency-Case Report and Literature Overview.

Background: Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that lead to the dysfunction of the steroidogenesis pathway, resulting in steroid hormone deficiency of varied intensity. The cholesterol side-chain cleavage enzyme (P450scc), coded by the CYP11A1 gene, is vital to the first step in the biosynthesis of steroid hormones, which is the conversion of cholesterol to pregnenolone. Therefore, its deficiency causes a general steroid hormone shortage.

Objective: We report a case of CAH caused by P450scc deficiency with complete 46, XY sex reversal, characteristic facial features (narrow middle section of the face, small ears with thick helix, fleshy upturned lobules), and dysmorphic macrocephaly along with shortened upper and lower extremities.

Results: Our patient carries a compound heterozygotic pathogenic variant of the CYP11A1 gene, with two frameshift pathogenic variants NM_000781.3(CYP11A1):c.358del (p.Arg120Aspfs*18) in exon 2 and NM_000781.3(CYP11A1):c.835del (p.Ile279Tyrfs*10) in exon 5. To date, only around 50 cases with CYP11A1 pathogenic variants have been reported worldwide. We believe this is the first described case of a newborn with severe, classic P450scc deficiency in Poland.

Conclusions: CYP11A1 (P450scc) deficiency is a rare and complex disorder that leads to primary adrenal insufficiency and may present with 46, XY disorders of sex development (DSD), phenotypic variations, and associated endocrinological abnormalities. This case, along with others cited, highlights the diverse presentations of DSD in individuals with pathogenic CYP11A1 variants. Optimal management necessitates a multidisciplinary approach by a specialized DSD team. Gonadectomy is a key consideration to decrease the teratogenic risk associated with intra-abdominal gonadal tissue.