Most common cause of ambiguous genitalia in neonates?

• A. Androgen insensitivity syndrome
• B. Congenital adrenal hyperplasia
• C. Turner syndrome
• D. Klinefelter syndrome

Answer: (B)

Congenital adrenal hyperplasia, typically due to 21-hydroxylase deficiency, is the most common cause of ambiguous genitalia in newborns. In affected 46,XX infants, excess fetal androgens from the adrenal glands virilize the external genitalia, leading to a spectrum from clitoromegaly to labioscrotal fusion that can present as ambiguous genitalia at birth. While other conditions like androgen insensitivity syndrome, Turner syndrome, or Klinefelter syndrome can also affect genital appearance, CAH accounts for the majority of neonatal cases. Classic CAH can present with salt-wasting and electrolyte disturbances, so early recognition and treatment with glucocorticoids (and mineralocorticoids if needed) are crucial. Diagnosis is supported by very high 17-hydroxyprogesterone levels and confirmed with further hormonal and genetic testing.