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Syndrome de klinefelter et conseil génétique

Genetic counselling in Klinefelter’s syndrome

Résumé

Le syndrome de Klinefelter a longtemps été considéré comme synonyme de stérilité masculine jusqu’à l’apparition des techniques d’ICSI. La possibilité pour des hommes à caryotype anormal d’avoir une descendance propre a, dès lors, posé la question du risque génétique pour cette dernière. Grâce aux méthodes d’analyse des chromosomes des spermatozoïdes, après fécondation hétérospécifique homme-hamster ou par hybridation in situ de sondes fluorescentes, il a pu être montré que les spermatozoïdes retrouvés chez un nombre non négligeable de sujets Klinefelter avaient le plus souvent un contenu chromosomique équilibré, ce qui a été confirmé par la normalité du caryotype de la plupart des enfants nés après ICSI à partir de ces hommes. Cependant, l’augmentation, faible mais significative chez eux, des spermatozoïdes disomiques pour les gonosomes laisse penser que leur spermatogenèse s’effectue dans un environnement testiculaire défavorable quant au contrôle de la ségrégation chromosomique à la méïose. Cette constatation peut être étendue aux autosomes et incite à la prudence dans le suivi génétique des grossesses.

Abstract

Klinefelter’s syndrome is a common sex chromosomal aberration generally characterized by hypergonadotrophic hypogonadism and azoospermia. However, spermatogenesis impairment is variable and severe oligozoospermia can be found in some men, particularly those exhibiting a mosaic karyotype 47,XXY/ 46,XY. New reproductive technologies, such as intracytoplasmic sperm injection (ICSI), allow Klinefelter patients to have a progeny, even those who are azoospermic after testicular sperm recovery. The question therefore arises of whether or not there is a genetic risk for pregnancies from affected fathers. Sperm karyotyping, by in vitro penetration of zona-free hamster eggs or by fluorescence in-situ hybridization (FISH), is a method of choice for measuring aneuploidy rate in spermatozoa of patients carrying gonosomal abnormalities. A theoretical model would predict a high level of 24,XX and/or 24,XY disomic sperm cells in Klinefelter patients if 47,XXY spermatogonia were able to complete meiosis and achieve spermatogenesis. Interestingly, current observations show that the rate of abnormal spermatozoa in these patients is low, around 1–2%, which indicates that only 46,XY spermatogonia can produce mature sperm cells and that oligozoospermic Klinefelter patients probably carry a 47,XXY / 46,XY mosaicism, at least at the testicular level. However, this low but statistically significant level of disomic spermatozoa emphasizes the fact that their spermatogenesis occurs in a compromised environment which could increase the risk of meiotic errors. Therefore, the possible occurrence of autosomal aneuploidies in children born from Klinefelter fathers leads to the following recommendations: a) individual analysis by FISH of the sperm aneuploidy rate in each Klinefelter patient candidate for ICSI; b) proposal of fetal karyotyping after amniocentesis in pregnancies obtained by this technique.

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Correspondence to J. P. Siffroi.

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Communication au XVIIème Congrès de la SALF, 7–8 décembre 2000, Bordeaux

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Siffroi, J.P. Syndrome de klinefelter et conseil génétique. Androl. 11, 9–14 (2001). https://doi.org/10.1007/BF03034505

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Mots clés

  • Syndrome de Klinefelter
  • FISH
  • ICSI
  • Conseil génétique

Key Words

  • Klinefelter’s syndrome
  • FISH
  • ICSI
  • genetic counselling
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