Disorders of sex development 45,X/46,XY: clinical and laboratory characteristics of patients

Aim. To study the clinical and laboratory characteristics of patients with disorders of sex development (DSD) 45,Х/46,ХY.
Materials and methods. The study included 248 patients with genital malformations from early neonatal period to 18 years. The group of patients with DSD 45,Х/46,ХY was formed according to the results of cytogenetic and molecular cytogenetic examination. Anthropometric data, external and internal genitalia, hormonal parameters in mini-pubertal, neutral and pubertal periods were assessed; histological examination of the gonads and screening of development malformations were performed.
Results. DSD of 46,ХY karyotype was revealed in 48% (120/248) cases, 46,ХХ DSD – 38% (93/248), DSD with sex chromosome pathology – 14% (35/248) patients. Chromosome DSD was represented by Klinefelter syndrome, Shereshevsky – Ulrich – Turner syndrome, chimeric DSD, and ovotesticular DSD, but the majority of patients had mosaicism 45,Х/46,ХY (65%). In the group of patients with NFP 45,X/46,XY, the median degree of masculinization of the external genitalia by the scale of the external masculinization score (EMS) was 3 [1; 5,5]. Among the defects of external genitalia in most cases (82%, 18/22) there was a combination of cryptorchidism with hypospadias. Derivatives of the Mueller ducts were detected in 91% (20/22) of patients. Most patients (77%) adapt the male passport field. There were no statistically significant differences in the structure of the external and internal genitalia between the groups of patients adapted in the male and female passport fields.
The analysis of hormonal indexes revealed a positive correlation between the content of basal testosteron
in the mini-pubertal period and the index of masculinization of the external genitalia by the EMS scale (p = 0,002; r = 0,9). In the period of mini-puberty an increase in the level of gonadotropic hormones was detected in 89% (8/9) of children, a combined increase of luteinizing and follicle-stimulating hormones (FSH) being observed in 33% (3/9), an isolated increase of FSH – in 56% (5/9) of cases. In the pubertal period hypergonadotropic hypogonadism was revealed in 75% (3/4) of patients.
The results of the histological study of the gonads were heterogenous. Gonads are represented by a different degree of dysgenesis of testicular tissue: from a mild, histologically-like gonad in cryptorchidism to streak and ovotestis.
Among the extragonadal manifestations of the disease, inguinal hernia (86%), heart defects (77%) and kidney defects (36%) are prominent. Pathological growth retardation was diagnosed in 23% of children.
Conclusion. In the structure of the disease chromosomal DSD accounts for 14% of observations. A group of patients with DSD 45,X/46,XY is heterogenous in the degree of gonadal dysgenesis, the structure of the external and internal genitalia.

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