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 language | English |
|---|---|
| Pages (from-to) | 28-36 |
| Number of pages | 9 |
| Journal | Sexual Development |
| DOIs | |
| Publication status | Accepted/In press - Apr 13 2016 |
| Externally published | Yes |
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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
5α-Reductase-2 Deficiency : Clinical Findings, Endocrine Pitfalls, and Genetic Features in a Large Italian Cohort. / Bertelloni, Silvano; Baldinotti, Fulvia; Russo, Gianni; Ghirri, Paolo; Dati, Eleonora; Michelucci, Angela; Moscuzza, Francesca; Meroni, Silvia; Colombo, Ilaria; Sessa, Maria R.; Baroncelli, Giampiero I.
In: Sexual Development, 13.04.2016, p. 28-36.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 5α-Reductase-2 Deficiency
T2 - Clinical Findings, Endocrine Pitfalls, and Genetic Features in a Large Italian Cohort
AU - Bertelloni, Silvano
AU - Baldinotti, Fulvia
AU - Russo, Gianni
AU - Ghirri, Paolo
AU - Dati, Eleonora
AU - Michelucci, Angela
AU - Moscuzza, Francesca
AU - Meroni, Silvia
AU - Colombo, Ilaria
AU - Sessa, Maria R.
AU - Baroncelli, Giampiero I.
PY - 2016/4/13
Y1 - 2016/4/13
N2 - 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.
AB - 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.
KW - 46,XY disorders of sex development
KW - 5α-Reductase-2 deficiency
KW - Molecular genetics
KW - SRD5A2 gene
KW - Testosterone/dihydrotestosterone ratio#
UR - http://www.scopus.com/inward/record.url?scp=84963606402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963606402&partnerID=8YFLogxK
U2 - 10.1159/000445090
DO - 10.1159/000445090
M3 - Article
AN - SCOPUS:84963606402
SP - 28
EP - 36
JO - Sexual Development
JF - Sexual Development
SN - 1661-5425
ER -