Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Simpson, Joe Leigh; Cruz, Felix de la; Swerdloff, Ronald S.; Samango‐Sprouse, Carole; Skakkebæk, Niels E.; Graham, John M.; Hassold, Terry; Aylstock, Melissa; Meyer‐Bahlburg, Heino F. L.; Willard, Huntington F.; Hall, Judith G.; Salameh, Wael A.; Boone, Kyle Brauer; Staessen, Cathérine; Geschwind, Dan; Giedd, Jay N.; Dobs, Adrian S.; Rogol, Alan D.; Brinton, Bonnie; Paulsen, C. Alvin

doi:10.1097/01.gim.0000095626.54201.d0

Cited by 177 publications

(170 citation statements)

References 54 publications

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“…This syndrome has a genetic basis but the risk of translation is almost impossible through natural conception. The supernumerary X chromosome is almost equally transmitted from both the mother and the father [6,7]. However this possibly does not pose the risk of genetic translation through consanguineous partners.…”

Section: Discussionmentioning

confidence: 99%

Parental Consanguinity in Infertile Males

Demirtaş¹,

Akınsal²,

Ekmekçioğlu³

2013

OJU

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This study was investigated whether parental consanguinity in males has an effect on or relationship with some infertile subgroups and some semen and hormone parameters. The charts of 2651 infertile males were evaluated retrospectively for parental consanguinity ratios, sperm counts, motility parameters and hormonal values from the records of 2651 infertile males. In 1260 eligible males the first cousin parental consanguinity ratio was 22.6%. In 119 males with nonobstructive azoospermic (NOA) and 430 males with normal sperm counts, the ratios were 34.5% and 20.9%, respectively (p = 0.002). In the NOA group the parental consanguinity ratios were 27.1% (23/85) and 52.9% (18/34) in males with FSH values of >7.6 and <7.6 mIU/ml, respectively (p = 0.007). In males with normal sperm counts if the parents were first cousins, both sperm counts and motility parameters were significantly reduced when compared with the others. To our knowledge, this is the first study of consanguinity ratios among some infertile subgroups. In males with parental consanguinity lower sperm counts and motility ratios in normozoospermic males and lower FSH levels in the NOA group might show a relation with some genetically transmitted defects.

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Section: Discussionmentioning

confidence: 99%

Parental Consanguinity in Infertile Males

Demirtaş¹,

Akınsal²,

Ekmekçioğlu³

2013

OJU

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“…The additional X chromosome results in a spectrum of clinical features ranging from infertility, small testes, testosterone deficiency, breast development, and decreased facial and pubic hair, to varying levels of specific cognitive, social, behavioural and learning difficulties (Simpson et al 2003). Despite these features, up to 70% of KS remains undiagnosed and of those that are detected, diagnosis is not usually made until later in adulthood (Bojesen et al 2003).…”

Section: Klinefelter Syndromementioning

confidence: 99%

“…Learning, speech and behavioural therapies are available from early childhood if required (Rovet et al 1996;Simpson et al 2003), and the most prevalent intervention for KS is testosterone treatment commencing in puberty, which can have both short-and long-term medical benefits in addition to profound positive psychosocial effects (Nielsen et al 1988). Therefore, the issues of both late diagnosis and nondiagnosis of KS are regarded as problematic, as these individuals may indeed benefit from available medical, educational and psychosocial interventions.…”

Section: Klinefelter Syndromementioning

confidence: 99%

Assessing the risks and benefits of diagnosing genetic conditions with variable phenotypes through population screening: Klinefelter syndrome as an example

et al. 2010

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Consideration of postnatal population-based genetic screening programs is becoming increasingly common. Assessing the medical and psychosocial impacts of this can be particularly complex for genetic conditions with variable phenotypes, especially when outcomes may be more related to quality of life rather than reducing physical morbidity and mortality. In this article, we present a framework for assessing these impacts, by comparing diagnosis and non-diagnosis at different age points. We use the example of Klinefelter syndrome, a common yet frequently under-diagnosed genetic condition for which interventions are available. This framework can be used to supplement established screening guidelines and inform decision-making.

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“…Less than 1% of newborns are trisomic, and clearly sex chromosome trisomies are less severe than those of autosomes (Thomas & Hassold 2003). Although maternal errors account for more than 95% of autosomal trisomies, it is notable that paternal errors account for 50% of cases of Klinefelter syndrome (KS: 47,XXY) (Simpson et al 2003).…”

Section: Introductionmentioning

confidence: 99%

“…KS occurs in 1 of every 1000 male births and is characterized by several features including infertility, typically azoospermia (no sperm in the semen), small testes and penis, Leydig cell hyperplasia, androgen deficiency, abnormally long limbs, sparse or absent facial, pubic or body hair, feminine distribution of adipose tissue, and increased frequencies of autoimmune disorders and learning disabilities (Smyth & Bremner 1998, Simpson et al 2003. It is reported that men with KS also have higher rates of sex chromosomal aneuploidy ranging from 0.1 to 50% and autosomal aneuploidy (of chromosomes 13, 18 and 21) in their sperm compared with normal fertile men (Moosani et al 1995, Martini et al 1996, Guttenbach et al 1997a, Estop et al 1998, Foresta et al 1998, Kruse et al 1998, Aran et al 1999, Lim et al 1999, Okada et al 1999, Rives et al 2000, Hennebicq et al 2001, Levron et al 2001, Morel et al 2003, Simpson et al, 2003, an observation paralleled by studies in 41,XXY mice (Mroz et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Recombination in men with Klinefelter syndrome

Gonsalves

Turek

Schlegel³

et al. 2005

Reproduction

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Klinefelter syndrome (KS: 47,XXY), occurs in one in 1000 male births. Men with KS are infertile and have higher rates of aneuploidies in sperm compared with normal fertile men. In the course of analyzing recombination in a population of infertile men, we observed that four men in our study presented with KS. We examined whether these men differed in recombination parameters among themselves and relative to normal men. Even though the number of men with KS analyzed was small, we observed remarkable variation in spermatogenesis. In spite of the fact that the men had the same genetic cause for infertility, two of four KS patients had few or no spermatogenic cells that progressed through meiosis to the pachytene stage, whereas the other two men produced abundant pachytene cells that had recombination frequencies comparable with those of fertile men, although one had a significant reduction in fidelity of synapsis. Moreover, regardless of histological appearance, examination of outcomes of assisted reproduction indicated that sperm were extracted from testis biopsies in all four cases, and when used in assisted reproductive practices chromosomally normal babies were born. These results reinforce that: (i) men with the same underlying genetic cause for infertility do not present with uniform pathology, (ii) the checkpoint machinery that might arrest spermatogenesis in the face of chromosomal abnormalities does not prevent pockets of complete spermatogenesis in men with KS, and (iii) aneuploidy, in some cases, is compatible with birth of a chromosomally normal child, suggesting that sperm produced from a background of aneuploidy can be normal in men with KS.

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Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Cited by 177 publications

References 54 publications

Parental Consanguinity in Infertile Males

Parental Consanguinity in Infertile Males

Assessing the risks and benefits of diagnosing genetic conditions with variable phenotypes through population screening: Klinefelter syndrome as an example

Recombination in men with Klinefelter syndrome

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