Updated: 8/31/2021

Klinefelter Syndrome

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  • Snapshot
    • A 30-year-old man presents to the physician with his wife with concerns that they have been unable to get pregnant after trying for the past year. The patient's wife has undergone a female infertility workup with no positive results. On physical examination, the man has scant hair in the axilla and pubic areas, small and firm testes, and the finding seen in the image. Karyotype testing is performed and reveals the presence of an extra X chromosome.
  • Overview
  • Introduction
    • Overview
      • Klinefelter syndrome is a sex chromosome disorder that is a common underlying cause of hypogonadism in men
    • Epidemiology
      • incidence
        • 1 to 2.5 per 1000 men
          • only 25-50% of Klinefelter syndrome patients are diagnosed during their lifetimes
      • risk factors
        • advanced maternal age
    • Pathophysiology
      • pathophysiology
        • male child is born with an extra, inactivated X chromosome
          • karyotype 47,XXY
          • nondisjunction during cell division prevents X chromosome from being distributed normally
        • dysgenesis of seminiferous tubules
          • results in primary testicular failure with ↓ androgen production
  • Presentation
    • Symptoms
      • infertility
      • signs of androgen deficiency
        • gynecomastia
          • breast development at puberty
        • sexual dysfunction
        • osteoporosis
    • Physical exam
      • female hair distribution
      • gynecomastia
      • long extremities
      • tall stature
      • small, firm testes
  • Studies
    • Karyotype
      • karyotype 47,XXY provides a definitive diagnosis
      • generally only recommended in prepubertal or pubertal boys, or men with clinical signs of Klinefelter syndrome who are seeking fertility treatment
    • Serum hormone levels
      • ↑ FSH and LH
      • ↓ testosterone
      • ↑ estradiol
        • due to ↑ expression of aromatase
  • Differential
    • Double Y males (47,XYY)
      • key distinguishing factor
        • phenotypically normal with intact fertility
    • Fragile X syndrome
      • key distinguishing factor
        • enlarged testes
    • Marfan syndrome
      • key distinguishing factor
        • intact fertility
  • Treatment
    • Medical
      • androgen (testosterone) replacement therapy
        • indications
          • promote development of normal male secondary sex characteristics
    • Lifestyle
      • speech and behavioral therapy
        • indications
          • improve speech impairments and psychosocial problems
  • Complications
    • ↑ risk of breast cancer
      • incidence
        • up to 50-fold ↑ incidence of male breast cancer compared to the normal population

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(M1.RP.15.73) A 30-year-old man presents for an infertility work-up. He and his wife have been unsuccessfully trying to get pregnant for 12 months. The patient has no known history of medical conditions. Physical exam was notable for features depicted in Figure A. Laboratory testing showed increased levels of FSH and LH.

Which of the following is the most likely explanation for this patient's presentation?

QID: 106542
FIGURES:

47 XYY chromosome disorder

1%

(2/201)

47 XXY chromosome disorder

75%

(151/201)

Chloride ion transporter defect

2%

(4/201)

Androgen insensitivity

18%

(36/201)

Defective migration of GnRH cells

1%

(3/201)

M 2 C

Select Answer to see Preferred Response

(M1.RP.15.6005) A 19-year-old male from rural West Virginia presents to his family medicine doctor to discuss why he is having trouble getting his wife pregnant. On exam, he is 6 feet 2 inches with a frail frame and broad hips for a male his size. He is noted to have mild gynecomastia, no facial hair, and small, underdeveloped testes. He claims that although he has a lower libido than most of his friends, he does have unprotected sex with his wife. His past medical history is notable for developmental delay and difficulties in school. What is the most likely chromosomal abnormality in this patient?

QID: 106967

Trisomy 13

1%

(1/168)

Trisomy 21

1%

(1/168)

47: XYY

8%

(14/168)

47: XXY

88%

(147/168)

45: XO

2%

(3/168)

M 2 D

Select Answer to see Preferred Response

(M1.RP.14.27) A young Caucasian couple in their late twenties present for an infertility evaluation after trying to conceive over 2 years. On physical exam, the female appears healthy and states that she has regular menstrual cycles. The male partner is noted to have long extremities with wide hips, low muscle mass, gynecomastia, sparse facial or chest hair, and small, firm testes. Laboratory tests of the male partner reveal elevated serum LH and FSH and low testosterone levels. If cytogenetic tests were performed, which of the following would be seen in this male?

QID: 107013

Presence of a barr body

75%

(91/121)

Absence of a barr body

8%

(10/121)

Absence of a second sex chromosome

7%

(9/121)

Trisomy of chromosome 13

1%

(1/121)

Trisomy of chromosome 18

6%

(7/121)

M 1 D

Select Answer to see Preferred Response

(M1.RP.13.1) A 25-year-old male visits his physician because of fertility issues with his wife. Physical exam reveals bilateral gynecomastia, elongated limbs, and shrunken testicles. Levels of plasma gonadotropins are elevated. Which of the following is also likely to be increased in this patient:

QID: 101663

Testosterone

3%

(5/194)

Inhibin

25%

(49/194)

Aromatase

66%

(128/194)

Ejaculatory sperm

0%

(0/194)

Sertoli cells

5%

(10/194)

M 2 D

Select Answer to see Preferred Response

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