Clinical and Laboratorial Features That May Differentiate 46,XY DSD due to Partial Androgen Insensitivity and 5α-Reductase Type 2 Deficiency

Abstract

The aim of this study was to search for clinical and laboratorial data in 46,XY patients with ambiguous genitalia (AG) and normal testosterone (T) synthesis that could help to distinguish partial androgen insensitivity syndrome (PAIS) from 5α-reductase type 2 deficiency (5α-RD2) and from cases without molecular defects in the AR and SRD5A2 genes. Fifty-eight patients (51 families) were included. Age at first evaluation, weight and height at birth, consanguinity, familial recurrence, severity of AG, penile length, LH, FSH, T, dihydrotestosterone (DHT), Δ4-androstenedione (Δ4), and T/DHT and T/Δ4 ratios were evaluated. The AR and SRD5A2 genes were sequenced in all cases. There were 9 cases (7 families) of 5α-RD2, 10 cases (5 families) of PAIS, and 39 patients had normal molecular analysis of SRD5A2 and AR genes. Age at first evaluation, birth weight and height, and T/DHT ratio were lower in the undetermined group, while penile length was higher in this group. Consanguinity was more frequent and severity of AG was higher in 5α-RD2 patients. Familial recurrence was more frequent in PAIS patients. Birth weight and height, consanguinity, familial recurrence, severity of AG, penile length, and T/DHT ratio may help the investigation of 46,XY patients with AG and normal T synthesis.

Correlation of androgen receptor and SRD5A2 gene mutations with pediatric hypospadias in 46, XY DSD children

“…According to studies, AIS and 5α reductase type-2 deficiency are the major causes of 46, XY DSD, accounting for about 50% of XY DSD (Mendonca et al, 2010). Through studies on clinical manifestations, biochemical examination, and genetic testing of 58 patients with 46, XY DSD, Veiga-Junior et al (2012) came to the following conclusions: for 46, XY DSD patients with undistinguishable genitals, SRD5A2 gene testing is the first option; for patients who have relevant family history, AR gene testing is the first option. This study involved 76 cases of 46, XY DSD patients; they had 46 chromosomes and their XY and SRY genes were normal, which ruled out the possibility that chromosomal abnormalities or SRY genes led to male gonad dysplasia.…”

Androgen insensitivity syndrome: discussion based on three cases

“…In patient with partial androgen insensitivity syndrome quantification of testosterone, dihydro testosterone, T/DHT ratio and post beta HCG stimulation T/DHT ratio is important to exclude defects in testosterone biosynthesis and 5 alpha reductase deficiencies. 4 The ectopic testis carries a overall risk of malignancy of 5-10% comprising of seminoma, dysgerminoma arising from the premalignant precursor called carcinoma in situ or intratubular germ cell neoplasia. Gonadal malignancy risk is even higher in partial androgen insensitivity syndrome with incidence of 15% or higher.…”

NR5A1 Gene Mutations: Clinical, Endocrine and Genetic Features in Two Girls with 46,XY Disorder of Sex Development

“…In complete AIS, birth weight, adjusted for gestational age and British references has been found to be slightly high for girls (0.4 SDS) and equivalent to reference values for boys (0.1 SDS) ] [31]. Although data for DSD according to national references have not been shown, birth weight and length seem to be slightly reduced in babies with 5α-reductase II deficiency (2,890 g and 48 cm, respectively) [32]. Since pregnancies of our girls were uncomplicated by known disorders causing large neonatal body proportions, the increased neonatal weight and length may be a distinctive feature of newborns with 46,XY DSD due to NR5A1 gene mutations, but more data are needed to draw clear conclusions on this issue.…”