A novel mutation in a case of XY DSD with progressive virilization at puberty

We present a case of ambiguous genitalia, not being evaluated at birth and presenting with progressive virilization at puberty. The usual set of differential diagnoses in a patient with the presence of bilateral gonads and progressive virilization includes five alpha-reductase deficiency, 17 beta-hydroxysteroid dehydrogenase 3 deficiency, partial androgen insensitivity syndrome, and partial gonadal dysgenesis. Human chorionic gonadotropin (HCG) stimulation test performed on our patient suggested the presence of five alpha-reductase deficiency with a testosterone/dihydrotestosterone (T/DHT) ratio of 32; however, the genetic analysis revealed the presence of autosomal dominant, heterozygous pathogenic mutation in NR5A1 gene Exon 5 with autosomal dominant heterozygous mutation in DHX37 gene Exon 18. While NR5A1 mutation is a known cause of testicular dysgenesis; DHX37 is a novel gene associated with ambiguous genitalia and there are only a few case reports presenting with a combined mutation. The patient exhibited a high T/DHT ratio on HCG stimulation and also exhibited poor virilization despite being on testosterone therapy for 2 years. Whether these mutations affect five alpha-reductase enzymes inhibiting testosterone to dihydrotestosterone conversion is unknown.