5α-Reductase-2 Deficiency: Clinical Findings, Endocrine Pitfalls, and Genetic Features in a Large Italian Cohort

Silvano Bertelloni, Fulvia Baldinotti, Gianni Russo, Paolo Ghirri, Eleonora Dati, Angela Michelucci, Francesca Moscuzza, Silvia Meroni, Ilaria Colombo, Maria R. Sessa, Giampiero I. Baroncelli

Research output: Contribution to journalArticle

Abstract

Clinical records (n = 24) with an established diagnosis of 5α-reductase-2 deficiency were reviewed. A previous misdiagnosis was present in about 70% (period from first observation to definitive diagnosis: 9.1 ± 10.8 years), and in 8 children gonadal removal was performed before certain diagnosis. Initial sex assignment was female in 16/24 (67%) and male in 8/24 (33%) cases. After diagnosis, sex re-assignment was performed in 5 babies (4 girls to male sex; 1 boy to female sex). Baseline testosterone/DHT ratio was diagnostic in 6/12 subjects (first months of life n = 4; puberty n = 2), while post-hCG testosterone/DHT ratio was diagnostic in all tested individuals (choosing both the cut-off value 15 or 10). Eighteen different mutations in the steroid-5α-reductase-2 (SRD5A2) gene were identified, 5 of which have never been reported. In conclusion, a time lag exists before the diagnosis of 5α-reductase-2 deficiency is established; sex assignment and gonadal removal may be performed before certain diagnosis. Sex re-assignment is usually female to male, but the contrary may occur. A large variability in clinical phenotypes and genetic mutations was present in this cohort. Accurate endocrine evaluation is recommended in babies possibly affected by 5α-reductase-2 deficiency, since the use of appropriate cut-off values of testosterone/DHT ratio after hCG stimulation may permit to select individuals for SRD5A2 gene analysis. A genotype-phenotype correlation was not found in this study.

Original languageEnglish
Pages (from-to)28-36
Number of pages9
JournalSexual Development
DOIs
Publication statusAccepted/In press - Apr 13 2016
Externally publishedYes

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Keywords

  • 46,XY disorders of sex development
  • 5α-Reductase-2 deficiency
  • Molecular genetics
  • SRD5A2 gene
  • Testosterone/dihydrotestosterone ratio#

ASJC Scopus subject areas

  • Developmental Biology
  • Embryology
  • Endocrinology, Diabetes and Metabolism

Cite this

Bertelloni, S., Baldinotti, F., Russo, G., Ghirri, P., Dati, E., Michelucci, A., Moscuzza, F., Meroni, S., Colombo, I., Sessa, M. R., & Baroncelli, G. I. (Accepted/In press). 5α-Reductase-2 Deficiency: Clinical Findings, Endocrine Pitfalls, and Genetic Features in a Large Italian Cohort. Sexual Development, 28-36. https://doi.org/10.1159/000445090