Abstract
Background and objective: Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy (47, XXY) and cause of male hypergonadotropic hypogonadism. It is characterized by an extreme clinical heterogeneity in presentation, including infertility, hypogonadism, language delay, metabolic comorbidities, and neurocognitive and psychiatric disorders. Since testosterone is known to have organizational, neurotrophic and neuroprotective effects on brain, the condition of primary hypogonadism could play a role. Moreover, given that KS subjects have an additional X, genes on the extra-chromosome could also exert a significant impact. The aim of this narrative review is to analyze the available literature on the relationship between KS and neuropsychiatric disorders.
Methods: To extend to the best of published literature on the topic, appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined.
Results: Both morphological and functional studies focusing on the brain showed that there were important differences in brain structure of KS subjects. Different psychiatric disorders such as Schizophrenia, autism, attention deficit hyperactivity disorder, depression and anxiety were frequently reported in KS patients according to a broad spectrum of phenotypes. T supplementation (TRT) was not able to improve the psychotic disorders in KS men with or without overt hypogonadism.
Conclusion: Although the risk of psychosis, depression and autism is increased in subjects with KS, no definitive evidence has been found in studies aiming at identifying the relationship between aneuploidy, T deficit and the risk of psychiatric and cognitive disorders in subjects affected by KS.
Keywords: Klinefelter Syndrome, Hypergonadotropic hypogonadism, testosterone, autism, schizophrenia, attention deficit, hyperactivity disorder, depression; anxiety.
Graphical Abstract
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