Table 3 The features of biological sex and individual characteristics in different types of major DSD, based on the major aetiological abnormality [18]
Type of DSD | Karyotype | Gonads | Phenotype | Wolffian (W)/Mullerian (M) structures | Hormonal profile | Clinical presentation/classical features |
|---|---|---|---|---|---|---|
A. Sex chromosome DSD | ||||||
Klinefelter’s syndrome | 47 XXY 46 XY/47XXY 48 XXYY | Bilateral testes-hyalinized | No genital ambiguity, eunuchoid male | W+/M− | Increased Gn levels, FSH > LH | Gynaecomastia, Azoospermia, Risk of male breast cancer and testicular cancer |
Turner syndrome | 45 XO 45 XO/46 XX 45 XO/46 XY | Bilateral streak ovaries (no oocytes) | Female, short stature, lack of secondary sexual features | W−/M+ | High FSH and LH | Primary amenorrhea, risk of gonadoblastoma if Y +, lymphedema, renal, and CVS anomalies |
Mixed gonadal dysgenesis | 45 XO/ 46 XY | Dysgenetic and streak gonad | Variable phenotype, second most common cause of genital ambiguity in neonate | W+ with ipsilateral testis, M+ with ipsilateral streak gonad | Increased Gn, variable testosterone, and AMH | Unilateral undescended testis, Urogenital sinus, Infertility, risk of gonadal malignancy and Wilm’s tumor |
46 XX/ 46 XY ovotesticular DSD | 46 XX/46 XY | Testis and ovary/ovotestis | Variable, ambiguous genitalia, | W+ if ipsilateral testis, M+ if ipsilateral absent testis | Â | Internal duct structures reflect ipsilateral gonad, risk of gonadal tumors |
B. 46 XY DSD | ||||||
a. Disorders of gonadal development | ||||||
46 XY complete gonadal dysgenesis | 46 XY | Bilateral streak gonads | Female phenotype, sexual infantilism | W−/M + | Low testosterone and AMH, high Gn | Primary Amenorrhea, clitoromegaly and UG sinus, risk of germ cell tumors |
Partial gonadal dysgenesis | 46 XY, 45 XO/46 XY | Bilateral dysgenetic testis | Variable phenotype, external genital anomalies, UDT | W+ (hypoplastic)/M− | Low testosterone | Risk of gonadal malignancy, ‘Male Turner syndrome’ |
46 XY ovotesticular DSD | 46 XY | Ovotestis, dysgenetic | Variable phenotype | W+/−‘hypoplastic, M− | High Gn | Rarely completely female or male |
Testicular regression syndrome | 46 XY | Bilateral absent testes | Variable phenotype, male in vanishing testes | W+ hypoplastic/M− | Low testosterone, high Gn, low AMH | Evidence of testicular function in utero + |
b. Abnormal genital development due to disorders in hormone synthesis or action | ||||||
1. Disorders in androgen synthesis | ||||||
Leydig cell hypoplasia/LH receptor defects | 46 XY | Bilateral testes | Female phenotype, sexual infantilism, short vagina, UDT | W+/−, M− | Low testosterone, high LH | Autosomal recessive inheritance |
Testosterone biosynthesis defects | 46 XY | Bilateral testes | Genital ambiguity, undermasculinized male | W+ (normal or hypoplastic)/M− (rarely blind vagina) | Low or absent testosterone response after bhCG stimulation | Female phenotype in more severe forms, risk of gonadal tumor and virilization at puberty in 17-BHSD deficiency |
5-alpha reductase type 2 deficiency | 46 XY | Bilateral testes | Variable virilization, pseudo vagina is common | W+/M− | Normal testosterone and AMH, T/DHT > 30 | Signs of virilization at puberty |
2. Disorders in androgen action | ||||||
Partial androgen insensitivity syndrome | 46 XY | Bilateral testes | Variable phenotype | W+/−hypoplastic, M- | Normal or high testosterone, AMH and LH | Risk of gonadal malignancy high in non-scrotal testis |
Complete androgen insensitivity syndrome | 46 XY | Bilateral testes | Female phenotype | W−, M−, vas and vessels present | Normal or high testosterone, AMH and LH | Low risk of testicular malignancy |
3. Disorders of AMH synthesis or action | ||||||
PMDS | 46 XY | Bilateral testes | Male | W+/M+ | Normal testosterone, low AMH | Bilateral undescended testes ± inguinal hernia |
C. 46 XX DSD | ||||||
a. Disorders of gonadal development | ||||||
46 XX pure gonadal dysgenesis | 46 XX | Bilateral streak ovaries | Normal female genitalia | W−/M+ | High FSH and LH, low estradiol | Sexual infantalism |
46 XX ovotesticular DSD | 46 XX | Ovotestis, dysgenetic | Variable phenotype | W−, M+ with variable development | High Gn, Beta hCG test positive | Ambiguous genitalia |
46 XX testicular DSD | 46 XX (90% SRY +) | Bilateral testes-atrophic | Normal male, similar to Klinefelter | W+/M− | High FSH and LH, low testosterone | Genital ambiguity if SRY - |
b. Disorders of genital development due to androgen excess | ||||||
Congenital adrenal hyperplasia | 46 XX | Bilateral ovaries | Virilized female, ambiguous genitalia in neonate | W− or limited, M+ | High 17-OH progesterone in 21-OH deficiency, high 11 DOC in 11-B-OH deficiency | Salt wasting in classical form, hypertension in 11 B-OH deficiency |