Study of 5 Alpha Reductase Enzyme Gene Mutations in a Group of Patients with 46XY Disorders of Sex Development

Abstract

Background Disorders of sex development (DSD) are a wide range of conditions with diverse features and pathophysiology that most often present in the newborn or the adolescent periods. Affected patients usually present with atypical genitalia like hypospadias, isolated micropenis and undescended testis. These clinical situations can often be difficult to manage, particularly in those cases where the sex rearing is uncertain. Aim of the Work Studying 5alpha reductase enzyme gene mutations (SRD5A2) in patients with 46XY DSD to detect its molecular characteristics. Patients and Methods This cross-sectional study was performed on 25 male patients with clinical, laboratory and genetic molecular analysis of SRD5A2 gene mutation fitting the diagnosis of 46XY DSD. To assess the degree of virilization external masculinization score (EMS) was used where EMS less than 7 is considered ambiguous. All parameters were evaluated at the pediatrics endocrinology clinic and genetics department, Ain Shams University from December 2019 to December 2020. Results Only 12 patients showed laboratory and molecular results compatible with the diagnosis of SRD5A2 gene mutation, The mean age of the patients was 3.64 ± 4.75 years. Results showed EMS of 4.3 denoting the high degree of genital ambiguity in our cases. Scrotum was bifid in 5 patients (41.6%), underdeveloped in 5 patients (41.6%) and fused in 2 patients (16.8%). Cryptorchidism was found in 4 patients only (33.3%). Four patients (33.3%) had normal urethral opening while hypospadias was present in 8 patients being perineal in 1 patient (8.3%), perineoscrotal in 5 patients (41.6%) and scrotal in 2 patients (16.6%). Micropenis was present in 7 patients (58.3%), four patients had 2 openings (33.3%) compared to a single opening in 8 patients (66.7%). Regarding type of SRD5A2 gene mutations 56.2% of mutations were Insertion deletion, 25% were Insertion, 12.5 % were Missense, 6.25% were Deletion. Conclusion This study demonstrated ten novel mutations of SRD5A2 gene were identified in association with 5alpha reductase enzyme deficiency. These mutations were reported among 12 patients with 46 XY DSD from total of 25 patients were fit for this study. No distinct relationships were observed between genotypic and phenotypic characteristics in the participants.