51. Disorders of sex development (DSD): gonadal dysgenesis, adrenogenital syndrome, SRY translocation, androgen receptor deficiency, androgen synthesis disorders.

Disorders of Sexual Development (DSD)

Disorders of Sexual Development (DSD) are a group of congenital conditions in which there is discordance between chromosomal sex, gonadal sex, and phenotypic (anatomical) sex.

These disorders arise from abnormalities in:

• sex chromosome constitution,
• gonadal differentiation,
• synthesis or action of sex hormones,
• development of internal and external genitalia.

Normal Sexual Development

Sexual development proceeds through three sequential levels:

1. Chromosomal sex → established at fertilization (XX or XY)
2. Gonadal sex → differentiation into testes or ovaries
3. Phenotypic sex → development of internal and external genitalia

Disruption at any level results in a DSD phenotype.

II. CLASSIFICATION OF DISORDERS OF SEXUAL DEVELOPMENT

Modern classification is based on karyotype.

Main Categories

1. Sex chromosome DSD
2. 2. 46,XY DSD
3. 3. 46,XX DSD

III. SEX CHROMOSOME DSD

Disorders caused by numerical or structural abnormalities of sex chromosomes, affecting gonadal development.

Examples

• Turner syndrome (45,X)
• Klinefelter syndrome (47,XXY)
• Mosaic karyotypes (45,X/46,XY)

Pathogenesis

1. Abnormal sex chromosome number.
2. Impaired gonadal differentiation.
3. Hormonal insufficiency.
4. Abnormal sexual development.

Clinical Features

• Gonadal dysgenesis
• Delayed or absent puberty
• Infertility
• Variable genital phenotype