Klinefelter Syndrome

Klinefelter syndrome, or 47,XXY, syndrome is among the most common genetic conditions in males. It is characterized by the presence of an additional X chromosome. While incidence estimates vary widely, pooled data indicate 1 in ~650 live male births are associated with the karyotype. Despite its wide prevalence, clinical providers are often unfamiliar with the clinical phenotype associated with this condition. In some cases, this may be due to the fact that symptom manifestation demonstrates variable penetrance. This also correlates with estimates that up to 75% of men with 47,XXY karyotypes never receive a formal diagnosis. However, when associated symptoms are present, they tend to adhere to a characteristic profile. Thus, knowledge of these domains holds significant clinical implications for improved screening, diagnosis, and timely treatment of affected individuals. As such, this chapter aims to review psychiatric comorbidities associated with 47,XXY, as well as the evidence base for the treatment of these conditions to the extent literature is available.