Objective: To study structure disorders of sex development (DSD) 46,XY by one center.
Subjects and Methods: It was included 60 patients with diagnosis DSD 46,XY at birth to 18 years. For all patients was conducted structural evaluation of the external (by External Masculinization Score, EMS, 0-12) and internal genitalia (by pelvic ultrasound, n=60, laparoscopy, n=20), hormonal research (testosterone, dihydrotestosterone, androstendione, anti-Mullerian hormone, AMH, inhibin B, follicle-stimulating hormone, luteinising hormone) in mini-puberty (n=28), neutral period (n=21) and puberty (n=11), molecular genetic studies Ion Torrent custom Ampliseq_DSD (n=37) and gene such us AR (n=14), SF1 (n=2), SRY (n=3), CYP21 (n=2), WT1 (n=2), histology of gonads removed (n=23 by 15 patients).
Gonadal dysgenesis criteria: derivats Mullerian duct, AMH <55 ng/ml in mini-puberty and AMH <85 ng/ml in neutral period [Edelsztein N.Y et al].
Results: A definitive diagnosis was received in 56% (33/60) of children with 46,XY DSD: disorders of gonadal (testicular) development - 37% (22/60), disorders in androgen synthesis or action - 15% (9/60), persistent Mullerian duct syndrome - 2% (1/60) with homozygous mutation AMH, Smith-Lemli-Opiz syndrome - 2% (1/60) with heterozygous mutation DCHR7.
Disorders of gonadal development include complete gonadal dysgenesis in 13% (3/22) cases (pathological mutation WT1, n=1; SRY, n=2), in 82% (18/22) of cases partial gonadal dysgenesis (pathological mutations SF1, n=2 и SRY, n=1; mutations in the genes SF1, n=1, ESR2, n=2, LHCGR1, n=1 pathological significance of today is not known), in 5% (2/22) ovotesticular DSD (mutation ZFPM2, n=1 with pathological significance of today is not known).
Disorders in androgen synthesis or action presented by total (44%, 4/9) and partial (56%, 5/9) androgen insensitivity syndrome in 100% patients with pathological mutations gene AR.
While ƴ 44% (27/60) of patients didn't have verified variant of nosological pathology (mutation in genes LHX1, n=1, HSD17B3, n=1, AR, n=1, ZFPM2, FOXF2, n=1 with pathological significance of today is not known).
Conclusion: Completed complex survey including molecular genetic analysis allowed to verify nosological variant of DSD 46,XY only in 56% (33/60) of patients.
Rating of nosological variants of DSD 46,XY by frequency: partial gonadal dysgenesis (67%, 22/33), androgen insensitivity syndrome (27%, 9/33), total gonadal dysgenesis (10%, 3/33), persistent Mullerian duct syndrome (3%, 1/33), ovotesticular (3%, 1/33), Smith-Lemli-Opiz syndrome (3%, 1/33). Mutations in genes involved in gonadal development detected in 28% (17/60) patients, dominant mutations by frequency AR (53%), SRY (17%), SF1 (12%), WT1 (6%), AMH (6%), DHCR7 (6%).
19 - 21 Sep 2019
European Society for Paediatric Endocrinology