From a Disabling Condition to a Variant of Normalcy: Neuropsychiatric Aspects.

Current studies suggest an elevated risk of developing psychiatric disorders among individuals with XXY, though the emerged symptoms are described as heterogeneous, atypical, and frequently transnosographic. The personality and behavior of Klinefelter syndrome (KS) patients have been described as shy, reserved, sensitive, and passive in childhood, which, jointly with neglected learning difficulties, may lead to secondary adaptation and behavioral problems during adolescence. The neuropsychological phenotype in adults affected by KS is highly variable. Impaired measures of verbal skills, high incidence of dyslexia, and social dysfunctions are among the most consistently reported behavioral phenotypes. KS patients may primarily manifest difficulties in social adjustment and in coping with social situations. Indeed, high levels of distress during social interactions are consistent with reports of social anxiety, social withdrawal, and shyness. In addition, studies on KS boys and adults unselected for psychiatric disorders support an increased prevalence of schizotypal traits, schizophrenia symptoms, and disorders that comprise psychosis, depression, anxiety, autism spectrum, and attention deficit/hyperactivity (ADHD). Anxiety and depression, along with low self-esteem and closure, are the most prevalent and debilitating affective symptoms among KS patients, while associations with bipolar disorders have rarely been reported. On the whole, research on KS patients shows that depression has a significant negative effect on the quality of life, in addition to being a leading cause of disability and a major risk factor for suicide. Treatment of Klinefelter syndrome requires to be analyzed in more depth to ascertain which intervention, psychological and/or pharmacological, proves to be the most helpful for patients to achieve more effective coping and adaptation to disease, as well as to ameliorate psychopathological symptoms and quality of life. All KS patients should receive a comprehensive psychological or psychiatric assessment to manage the increased risk of anxiety, depression, and psychosis or behavioral disorders. Group psychotherapy could be beneficial to KS patients for expressing and sharing their sense of shame and isolation and for getting the support of peers. Psychological intervention as well would be helpful in executing the most profitable strategies to enhance the poor pharmacological compliance of KS subjects.