Differential Diagnosis for Big Testis and Small Penis

• Single most likely diagnosis
  • Klinefelter syndrome: This genetic condition is characterized by an extra X chromosome in males (XXY), often presenting with testicular enlargement and underdeveloped genitalia, including a smaller penis.
• Other Likely diagnoses
  • Androgen insensitivity syndrome: A condition where the body is partially or completely unable to respond to androgens, leading to underdeveloped male genitalia, which can include a smaller penis, but testicular size can vary.
  • Cryptorchidism: Undescended testes can sometimes be mistaken for enlarged testes if they are palpable in an abnormal location, and it can be associated with smaller penis size due to hormonal imbalances during fetal development.
• Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)
  • Testicular cancer: Although testicular cancer typically presents with a testicular mass rather than uniform enlargement, any significant change in testicular size warrants investigation to rule out malignancy.
  • Leydig cell tumors: These rare tumors can produce excess androgens or estrogens, potentially affecting genital development, but more importantly, they can be malignant and require early detection.
• Rare diagnoses
  • Myotonic dystrophy: A genetic disorder that can affect muscle tone and lead to testicular atrophy, but in some cases, it might present with testicular changes and could be associated with genital abnormalities.
  • Congenital adrenal hyperplasia: Certain forms of this condition can lead to ambiguous genitalia or underdeveloped male genitalia due to enzyme deficiencies affecting steroid hormone production.