Reprint of "Steroid 5α-reductase 2 deficiency".

Area of Science:

• Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Dihydrotestosterone (DHT) is a crucial androgen metabolite derived from testosterone via 5α-reductase isoenzymes.
• Mutations in the 5α-reductase type 2 gene lead to 5α-reductase type 2 deficiency, a disorder affecting 46,XY sex development.
• This condition, identified 40 years ago, involves diverse mutations across ethnic groups.

Approach:

• Review of genetic mutations and clinical presentations of 5α-reductase type 2 deficiency.
• Analysis of phenotypic outcomes, including external genitalia, internal reproductive tracts, and pubertal virilization.
• Evaluation of fertility, social sex development, and quality of life in affected individuals.

Key Points:

• Affected 46,XY individuals typically exhibit female external genitalia but male internal urogenital tracts due to DHT deficiency.
• Despite being often raised as females, most individuals experience significant virilization at puberty, leading to male social sex development.
• Fertility is achievable through assisted reproduction, and male social sex is associated with improved quality of life.

Conclusions:

• 5α-reductase type 2 deficiency presents a complex interplay between genetic mutations and sexual development.
• Pubertal virilization and the potential for male social sex development are key features of the condition.
• Management strategies should consider reproductive potential and psychosocial well-being to enhance quality of life.