Klinefelter Syndrome Differential Diagnoses

Updated: Jan 31, 2022
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Diagnostic Considerations

The physical findings in patients with Klinefelter syndrome vary. When the following features are present in an undiagnosed male, a chromosome analysis may be indicated:

  • Small testes (only consistent phenotypic feature in 47,XXY males)
  • Gynecomastia
  • Long arms and legs
  • Developmental delay
  • Speech and language deficits
  • Psychosocial difficulties/behavioral concerns
  • Learning disabilities/academic issues
  • Infertility

Other causes of hypogonadism should also be considered. These include Kallmann syndrome and 46,XX karyotype (in males). The 46,XX male is caused by translocation of Y material (including the sex-determining region [SRY]) to the X chromosome during paternal meiosis. The presence of SRY on the X chromosome leads to normal male sexual development with male external genitalia, but hypospadias or cryptorchidism may be seen. [40]

Differential Diagnoses