Pubertal development in 46,XY patients with NR5A1 mutations

Area of Science:

• Genetics and Endocrinology
• Reproductive Medicine
• Developmental Biology

Background:

• NR5A1 gene mutations are linked to diverse genital phenotypes in 46,XY differences of sex development (DSD).
• Steroidogenic Factor-1 (SF-1) plays a critical role in adrenal and gonadal development.

Purpose of the Study:

• To analyze pubertal development in 46,XY patients with NR5A1 mutations.
• Evaluate longitudinal clinical and hormonal data during puberty.

Main Methods:

• Retrospective study of 10 46,XY patients with verified NR5A1 mutations.
• Assessment of external/internal genitalia, testicular volumes, Tanner stages, and hormone levels (LH, FSH, testosterone, AMH, inhibin B).

Main Results:

• Spontaneous virilization observed at puberty in patients presenting with ambiguous genitalia in infancy, despite decreased gonadal volume.
• Patients with female external genitalia at birth showed later virilization or absent female puberty, with variable testosterone levels.
• Consistently elevated gonadotropins (LH, FSH) in all patients; no reliable correlation between birth phenotype and pubertal virilization.

Conclusions:

• Significant pubertal virilization can occur in NR5A1 mutation patients irrespective of their initial phenotype.
• Emphasizes the need for careful sex assignment decisions in infancy.
• Recommends avoiding irreversible procedures in early infancy for 46,XY DSD patients with NR5A1 mutations.