5α-Reductase-2 deficiency: is gender assignment recommended in infancy? Two case-reports and review of the literature.

PURPOSE: Gender assignment represents one of the most controversial aspects of the clinical management of individuals with Differences of Sex Development, including 5α-Reductase-2 deficiency (SRD5A2). Given the predominant female appearance of external genitalia in individuals with SRD5A2 deficiency, most of them were assigned to the female sex at birth. However, in the last years the high rate of gender role shift from female to male led to recommend a male gender assignment. METHODS: We here describe two cases of subjects with SRD5A2 deficiency assigned as females at birth, reporting their clinical histories and psychometric evaluations (Body Uneasiness Test, Utrecht Gender Dysphoria Scale, Bem Sex-Role Inventory, Female Sexual Distress Scale Revised, visual analogue scale for gender identity and sexual orientation) performed at the time of referral at the Florence Gender Clinic. RESULTS: Both patients underwent early surgical interventions without being included in the decision-making process. They had to conform to a binary feminine gender role because of social/familiar pressure, with a significant impact on their psychological well-being. Psychometric evaluations identified clinically significant body uneasiness and gender incongruence in both subjects. No sexually related distress and undifferentiated gender role resulted in the first subject and sexually related distress and androgynous gender role resulted in the second subject. CONCLUSIONS: The reported cases suggest the possibility to consider a new approach for gender assignment in these individuals, involving them directly in the decision-making process and allowing them to explore their gender identity, also with the help of GnRH analogues to delay pubertal modifications.

Phenotype, genotype and gender identity in a large cohort of patients from India with 5α-reductase 2 deficiency.

Deficiency of the 5α-reductase 2 enzyme impairs the conversion of testosterone to dihydrotestosterone (DHT) and differentiation of external genitalia, seminal vesicles and prostate in males. The present study describes the phenotype, genotype and gender identity in a large cohort of patients with 5αRD2. All patients underwent detailed clinical evaluation, hormonal profile, karyotyping and molecular analysis of the SRD5A2 gene. The molecular analysis of the SRD5A2 gene showed the presence of mutant alleles in 24 patients. We found 6 novel mutations IVS(1-2) T>C, p.A52T, 188-189insTA, 904-905ins A, p.A12T and p.E57X in our patients. All patients had ambiguous genitalia and the degrees of under-virilization ranged from penoscrotal hypospadias and microphallus to clitoromegaly. The position of gonads was variable in patients with same mutation. All the patients with mutations in the SRD5A2 gene had male gender identity. Those reared as female had gender dysphoria and underwent gender reassignment. Though a specific genotype-phenotype correlation could not be established in our patient but confirming the diagnosis of 5αRD2 with assessment of the SRD5A2 gene may help in appropriate gender assignment.