Klinefelter syndrome or testicular dysgenesis: Genetics, endocrinology, and neuropsychology

Klinefelter syndrome (47,XXY) is a frequent chromosomal disorder among males, often presenting with hypergonadotropic hypogonadism, small firm testicles, metabolic disorders, neurocognitive challenges, and increased height. Neurologic disorders such as epilepsy, seizures, and tremor as well as psychiatric disorders are also seen more frequently. The neurocognitive deficits seen are present in many areas of cognition, typically affecting general cognitive abilities, language, and executive functioning. Also, social dysfunction is frequent. Dyslexia is present in more than half of all males. Brain imaging studies generally show a typical pattern, with many nuclei and brain areas being smaller than among controls. However, it has not been possible to link the brain alterations found in imaging studies with the neurocognitive profile. The genetics underlying the phenotypic traits found among males with Klinefelter syndrome still remains to be elucidated; however, recent studies have described pervasive changes in the methylome and transcriptome and new and interesting candidate genes have been pinpointed, but their involvement in the phenotype of Klinefelter syndrome has not been proven.