[Harry Fitch Klinefelter, Jr. (1912–1990), American rheumatologist and endocrinologist at Johns Hopkins Medical School]

47,XXY (rarely XXYY) chromosomal abnormality

Frequency: 1÷750 live births (probably commonest chromosomal aberration)

• testicular atrophy (hyalinization of seminiferous tubules) = small / absent testes, sterility (azoospermia)
• eunuchoid constitution: gynecomastia; paucity of hair on face + chest; female pubic escutcheon; mild mental retardation
• high level of urinary gonadotropins + low level of 17-ketosteroids after puberty
• NO distinctive radiological findings!
• may have delayed bone maturation
• failure of frontal sinus to develop
• small bridged sella turcica
• ± scoliosis, kyphosis
• ± coxa valga
• ± “metacarpal” sign (short 4^th metacarpal)
• accessory epiphyses of 2^nd metacarpal bilaterally

Cx: breast cancer (3% risk + 20-fold increase in incidence due to elevated estrogen÷androgen ratio)