Klinefelter syndrome: clinical and molecular aspects

Abstract

Klinefelter syndrome is the most common chromosome abnormality in humans. The estimated prevalence is one in 500 to one in 1000 males but due to the widely variable and often aspecific features, only one in four cases are recognized. The most specific clinical features which can be observed at adult age are small testes, gynecomastia, female distribution of fat and body hair, slightly increased body length due to an increased leg length and azoospermia. Cognition is characterized by verbal deficits and psychosocial features include autistiform behavior. Structural brain abnormalities have been observed by MRI, such as decreased brain volumes and a decrease of asymmetry in areas corresponding to language performance. In the vast majority of cases a non-mosaic 47,XXY karyotype is observed. Parental imprinting of the extra X chromosome, variable inactivation of some X-chromosomal genes and CAG repeat length polymorphism of the androgen receptor may all be related to the variability of the phenotype. Surgical procedures of obtaining sperm in combination with repeated intracytoplasmic sperm injection/in vitro fertilization treatment may allow up to one in four men with Klinefelter syndrome to father children.

Aberrant Gene Expression Profiles in Pluripotent Stem Cells Induced from Fibroblasts of a Klinefelter Syndrome Patient

“…4B). In fact, the metabolic syndrome is one of important clinical features of KS (1). Gene Ontology analysis also revealed distinct properties of the KSiPSCs.…”

“…There is currently no effective treatment for KS. Intracytoplasmic sperm injection with spermatozoa obtained by testicular sperm extraction techniques would give some KS males a chance to father a child, whereas for most of the patients, infertility is still unresolved due to the failure of sperm retrievals or spermatogenesis (1,2). Therefore, further understanding of the disease and developing new strategies are required for effective treatment of KS.…”

The genetic origin of Klinefelter syndrome and its effect on spermatogenesis

“…Together with these successes, concerns about the risk of (sex chromosomal) aneuploidy in these children have been raised. However, even though the aneuploidy rate of sperm from Klinefelter men appears to be increased compared with fertile controls (46), the risks for the offspring appear to be small, with 1 XXY pregnancy in more than 100 children born after TESE-ICSI in males with nonmosaic Klinefelter syndrome reported in the literature (7). How can this low (sex chromosomal) aneuploidy rate in children born from Klinefelter fathers be explained?…”

“…Most men with Klinefelter syndrome are diagnosed when they have failed to achieve a pregnancy and are diagnosed with azoospermia. However, a significant proportion of men with Klinefelter syndrome remain undiagnosed, probably because of the wide phenotypic variability and lack of knowledge of the syndrome among health professionals (3,7).…”

Digit ratio (2D:4D) in Klinefelter's syndrome

“…Thus, the frequency of KS rises to about 3-4% among male patients that are infertile and to about 10-12% in male patients that are azoospermic (Forti et al, 2010). In such individuals, testicular biopsies may yield spermatozoa for successful intracytoplasmic sperm injection (ICSI) and in vitro fertilization treatment (Giltay & Maiburg, 2010). …”