[What is the interest of Klinefelter's syndrome for (child) psychiatrists?].

Klinefelter's syndrome (KS) concerns men and is usually characterized by tallness, underdeveloped testes and sterility. It is generally due to the 47,XXY genotype, ie one extra X chromosome in each cell. Its estimated frequency among newborn boys is 1/500 to 1/700. It seems that 64% KS would be undiagnosed. Abnormally low levels of testosterone blood values are very common in this syndrome. In this case, replacement androgen therapy should be initiated (ideally at the age of 11-15) which prevents osteoporosis and enhances secondary sexual features. Case report - Since early childhood, Mr X has been shy, passive with few friends. When he was 13 years old, the school physician noted a delay of puberty and referred him to an endocrinologist who diagnosed KS. Androgen therapy was introduced but rapidly stopped, because the boy and his parents thought it was useless. Mr X consulted a psychiatrist at the age of 21. He presented a schizo-affective disorder with influence syndrome, auditory and visual hallucinations, labile mood with disinhibited and depressive periods. He was admitted in a psychiatry ward of a general hospital. An endocrinologist confirmed the diagnosis of KS and found very low blood testosterone levels. Besides lithium and risperidone which had already been introduced before the hospitalization, androgens (testosterone undecanoate) were very progressively given to Mr X with a daily psychiatric evaluation. One month after discharge, a major depressive episode led to the adjunction of citalopram. After one year of follow-up, Mr X shows increased social adjustment and enhanced interest; the influence syndrome has partially regressed and his mood is more stable. Discussion - In the years '60 and '70, systematic screenings in psychiatric hospitals have detected 1.3% KS among hospitalized boys, ie 10 times more than in the general population, and 0.6 to 1% KS among hospitalized men. A large variety of psychiatric disorders have been described. Boys presenting KS are usually described as shy, with little energy and initiative, and few friends. They cry more often than compares. Neuropsychological studies demonstrate significantly lower verbal IQ than controls, while performance IQ is generally normal and global IQ is in the normal range with large individual variations. Language acquisition is always delayed. However, agressiveness is not increased. In his follow-up study of 20 years, Nielsen at al found more psychiatric disorders among KS patients, compared to a group of hypogonadal patients at first examination (mean age=27 years). After 20 years follow-up, however, no significant difference remained between the two cohorts concerning the frequency of psychiatric hospitalizations or mental diseases. Several hypotheses have been proposed to explain psychological aspects of KS such as low levels of androgens during foetal and child development, personality disorder related to hypogonadism, delay of mitosis of cells with an extra X chromosome, but none of them is able to explain the specificity of psychological problems associated with KS. Concerning therapeutic aspects, specialists prone substitutive androgen therapy in case of too low testosterone blood levels, from the time of increase in FSH (around the age of 11-15). It prevents osteoporosis, backache and excessive tiredness often found in males with KS; testosterone also improves social drive, mood, concentration and ability at work. If KS diagnosis is made at adult age, androgen therapy has also shown some efficacy, though less than if started earlier. Due to the oral and written language problems of KS boys between 5 and 12 years of age, Graham et al. recommend anticipatory guidance for these boys. In addition, they insist on the importance of the information of the parents, language therapy, the reduction of the length of the instructions given by schoolmasters and specially stimulating and stable childhood conditions. Though it is generally thought that androgens increase agressiveness, we found no consistent data in litterature proving that the restoration of physiological androgen blood levels increases crimes nor aggressiveness. In the contrary, Miller and Sulkes described four cases of KS men presenting chronic fire-setting behaviors. Testosterone was introduced. For three of them, follow-up was available: their behavior seemed improved and none of them recurred. However, the initiation of androgen therapy for patients with severe psychiatric illness should be done very carefully. Conclusion - The Klinefelter's syndrome is frequent and, if not diagnosed (which seems to be the most common case), these men have higher risks to develop psychiatric disorders. Therefore, child psychiatrists and psychiatrists should evoke that diagnosis when they examine boys or men who present typical physical traits of KS (tallness, underdevelopped testes) associated to school problems and/or psychiatric disorders. Indeed, if the diagnosis is confirmed by an endocrinologist and a genetic testing, psychological follow-up and testosterone undecanoate treatment (in case of abnormal testosterone blood levels) should be initiated. This therapy generally improves physical well-being and improves mood, concentration, capacity at work. There is no consistent data in the litterature proving that restoring physiological testosterone blood levels would be dangerous for KS men presenting severe psychiatric troubles. However, this should be discussed in each situation with caution, and androgens should be introduced very progressively.