Klinefelter's syndrome

(Harry Klinefelter, 20th century, American physician), a syndrome seen in individuals with two or more X chromosomes and one or more Y chromosomes. These individuals are hypogonadic males. The majority of affected individuals are of 47,XXY karyotype (82% of cases). Meiotic nondisjunction accounts for the extra chromosome, which may be of either maternal or paternal origin. Advanced maternal age and irradiation of either parent are risk factors.

Klinefelter's syndrome occurs in 1 in 850 live male births, making it a common genetic disease involving the sex chromosomes and the most common cause of male hypogonadism. Hypogonadism is seen in all cases, resulting in elevated gonadotropin levels (especially FSH) and variably reduced testosterone levels. Mean plasma estradiol levels are elevated by an unknown mechanism. The ratio of oestrogens to testosterone determines the extent of femininization. Clinical symptoms are usually not evident until puberty. They include: small atrophic testes with a small penis, eunuchoid body habitus with abnormally long legs, lack of secondary male sexual characterisitics and gynecomastia. The mean IQ is usually lower than that of the general population.

Patients with Klinefelter's syndrome are infertile. Azoospermia is seen related to testicular atrophy. In some patients, complete atrophy of the testicular tubules is present and they are replaced by pink, hyaline, collagenous ghosts. In others, apparently normal tubules are interspersed with atrophic tubules. In still others, all tubules are incompletely developed, consisting of cords of cells that have never developed a lumen or progressed to mature spermatogenesis. While some authors contend that Leydig cell hyperplasia is present in patients with Klinefelter's syndrome, others argue that the Leydig cell appears hyperplastic only because of atrophy and crowding of the tubules. In polysomic X individuals (e.g. 48, XXXY or 49, XXXXY), additional genital abnormalities are seen, including cryptorchidism, hypospadias, and more severe testicular hypoplasia.

Diagnosis of Klinefelter's syndrome is primarily based on clinical examination, supported by serum chemistries and chromosomal analysis. MRI and ultrasound play supporting roles in evaluating testicular abnormalities, but imaging is not crucial in the diagnosis of this syndrome.

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