✅ Model Answer:
• Diagnosis: Mixed gonadal dysgenesis (45,X/46,XY mosaic).
• Evidence: Ambiguous genitalia with a single perineal opening, unilateral testis (right), contralateral streak gonad, small uterus (Müllerian remnants), low AMH (from testicular tissue), 45,X/46,XY karyotype.
• Next step: Gonadectomy of the streak gonad (high risk of gonadoblastoma). Sex of rearing based on phallic development. If male sex of rearing, testosterone therapy for penile growth. If female, estrogen replacement at puberty. Multidisciplinary care (endocrinology, surgery, psychology).

✅ Model Answer:
• Karyotype: 45,X/46,XY mosaicism (most common).
• Prevalence: Rare (1 in 15,000-20,000 live births).
• Mechanism: Post-zygotic loss of the Y chromosome in some cell lines → mosaic 45,X/46,XY.
• Pathophysiology: The presence of the Y chromosome leads to testicular development in some tissues, while the 45,X cell line causes streak gonads (dysgenetic). This results in asymmetric gonadal development (unilateral testis, contralateral streak gonad).
• Phenotype: Ambiguous genitalia, Müllerian remnants (uterus), and variable virilization.
• Associated features: May have Turner-like features (short stature, webbed neck) if the 45,X cell line predominates.

✅ Model Answer:
• Neonatal:
- Ambiguous genitalia: Clitoromegaly, labioscrotal fusion, or microphallus.
- Single perineal opening (urogenital sinus).
- Palpable gonad on one side (usually testis) and contralateral streak gonad (non-palpable).
- Müllerian remnants: Small uterus and fallopian tube on the side of the streak gonad.
• Childhood/Adolescence:
- Virilization: May occur at puberty if the testis is functional.
- Short stature (if 45,X cell line is prominent).
- Primary amenorrhea (if raised female).
- Infertility.
- Gonadal malignancy risk: High risk of gonadoblastoma in the streak gonad (30-50%).

✅ Model Answer:
• Karyotype: 45,X/46,XY mosaic (confirmatory).
• Pelvic ultrasound/MRI:
- Unilateral testis (inguinal or abdominal).
- Contralateral streak gonad.
- Uterus (Müllerian remnant).
• Hormonal studies:
- AMH: Low (from testicular tissue).
- Testosterone: Variable (may be low or normal for age).
- FSH/LH: May be elevated if gonadal dysfunction.
- Electrolytes: Normal (no salt-wasting).
• Gonadal biopsy: To evaluate for malignancy (if gonad is preserved).
• Genetic testing: SRY gene (present in some cell lines).
• Urinalysis: To rule out renal anomalies (associated with Turner features).

✅ Model Answer:
• Gonadectomy:
- Streak gonad: Must be removed (high risk of gonadoblastoma – 30-50%).
- Testis: May be preserved if the patient is raised male (with careful monitoring for malignancy).
- If raised female: Both gonads should be removed (streak and testis) to prevent virilization at puberty and malignancy.
• Sex of rearing:
- Based on: Phallic development, gonadal function, and potential for fertility.
- Usually: If phallus is adequate, male sex of rearing is chosen; if phallus is inadequate, female sex of rearing is chosen.
• Hormone replacement:
- If raised male: Testosterone replacement at puberty.
- If raised female: Estrogen replacement at puberty.
• Uterus: If raised female, the uterus can be preserved (for potential fertility via egg donation).
• Multidisciplinary care: Endocrinology, surgery, psychology, genetics.

✅ Model Answer:
• Gonadoblastoma:
- Risk: 30-50% in the streak gonad (highest risk of all DSDs).
- Prevention: Prophylactic gonadectomy.
• Infertility: If both gonads are removed or dysgenetic.
• Short stature: If 45,X cell line is prominent (Turner-like features).
• Virilization: At puberty if the testis is left in place (in a female-raised patient).
• Psychosocial: Gender identity, body image, coping with ambiguous genitalia.
• Renal anomalies: Associated with Turner features (horseshoe kidney).

✅ Model Answer:
• Prognosis:
- Good with early gonadectomy and appropriate sex of rearing.
- Quality of life: Good with multidisciplinary care.
- Fertility: Usually not possible (if both gonads are removed); but if raised female, oocyte donation + IVF (if uterus is present).
- Life expectancy: Normal.
• Long-term follow-up:
- Monitor hormone replacement.
- Monitor for complications.
- Psychosocial support.
- Genetic counseling.

✅ Model Answer:
• Mixed Gonadal Dysgenesis (MGD):
- Karyotype: 45,X/46,XY mosaic.
- Gonads: Unilateral testis + contralateral streak gonad.
- Genitalia: Ambiguous (clitoromegaly, labioscrotal fusion, urogenital sinus).
- Müllerian structures: Uterus is present.
- AMH: Low (from testicular tissue).
- Testosterone: Variable.
- Malignancy risk: Very high (gonadoblastoma in streak gonad).
- Treatment: Gonadectomy + sex of rearing.
• Swyer syndrome:
- Karyotype: 46,XY.
- Gonads: Bilateral streak gonads (no testicular tissue).
- Genitalia: Female (normal female external genitalia).
- Müllerian structures: Uterus is present.
- AMH: Undetectable.
- Testosterone: Low/undetectable.
- Malignancy risk: High (gonadoblastoma).
- Treatment: Gonadectomy + estrogen replacement.
- Genetics: SRY mutation (most common).