Socio-economic factors affect mortality in 47,XYY syndrome-A comparison with the background population and Klinefelter syndrome.

Mortality among males with 47,XYY is increased due to a host of conditions and diseases. Clinical studies have suggested a poorer educational level and social adaptation among 47,XYY persons. We wanted to study the socio-economic profile in 47,XYY persons and the impact on mortality. We conducted a register study using several Danish nationwide registries. 206 47,XYY men and 20,078 controls from the background population and 1,049 controls with Klinefelter syndrome were included. Information concerning marital status, fatherhood, education, income, and retirement were obtained. Compared to the background population, 47,XYY men had fewer partnerships, were less likely to become fathers, had lower income and educational level, and retired at an earlier age. The mortality among 47,XYY men was significantly increased with a hazard ratio (HR) of 3.6 (95% confidence interval: 2.6-5.1). Adjusting for marital and educational status reduced this HR to 2.7. Compared to Klinefelter syndrome, 47,XYY had significantly fewer partnerships, were more likely to become fathers, but had lower income. Mortality among 47,XYY men was increased compared with Klinefelter syndrome with a HR of 1.36. The results show a severely inferior outcome in all investigated socio-economic parameters compared to the background population and an affected profile compared with Klinefelter syndrome, even though the population in Denmark has equal and free access to health care and education. We conclude that 47,XYY is often associated with a poorer socio-economic profile, which partly explains the increased mortality.

Morbidity and mortality in Klinefelter syndrome (47,XXY).

UNLABELLED: Klinefelter syndrome (KS) (47,XXY) is the most common sex chromosome disorder in man and is a relatively common cause of male infertility and hypogonadism. The syndrome has been known since 1942, and many reports of different diseases associated with KS have been reported since that, but a more systematic knowledge about the long-term outcome was not described until the last decade, where nation-wide epidemiological studies were reported from Britain and Denmark. We here review the epidemiological data from two cohorts of patients with KS in Denmark and Britain, showing a significant increase in both mortality and morbidity from a variety of different causes. Mortality was increased by 50% (SMR 1.5 or HR 1.4) corresponding to a median loss of approximately 2 years. The risk of being admitted to hospital with any diagnosis was increased by 70%. The underlying reason for the poorer health in KS may be caused by interaction of genetic, hormonal and socio-economic factors. CONCLUSION: Both morbidity and mortality are significantly increased in Klinefelter syndrome with a 50% increase in mortality risk and a 70% increase in risk of being admitted to hospital.

New incidence, prevalence, and survival of Aicardi syndrome from 408 cases.

We sought to determine the incidence, prevalence, and life expectancy of Aicardi syndrome from 408 cases compiled from multiple international sources. Last known age ranged from less than 1 month to 42 years. The incidence rates per live births for the United States and The Netherlands were 1 per 105 000 and 1 per 93 000, respectively. The prevalence in the United States is greater than 853 cases, and the worldwide estimate is several thousand. Forty-five cases were deceased (age range, 1 month to 33 years), and the risk of death peaked at age 16. The probability of survival at 27 years of age was 0.62 (95% CI, 0.47-0.77). The risk of death by age follows other congenital neurological disorders with a wide range in severity of functional disability. The longer life expectancy found in our study hints at a higher functioning capacity in Aicardi syndrome and may inform counseling to families.

Mortality in patients with Klinefelter syndrome in Britain: a cohort study.

CONTEXT: Klinefelter syndrome is characterized by hypogonadism and infertility, consequent on the presence of extra X chromosome(s). There is limited information about long-term mortality in this syndrome because there have been no large cohort studies. OBJECTIVE: Our objective was to investigate mortality in men with Klinefelter syndrome. DESIGN AND SETTING: We obtained data about patients diagnosed with Klinefelter syndrome at almost all cytogenetics centers in Britain, as far back as records were available, and conducted a cohort study of their mortality, overall and by karyotype. PATIENTS: We assessed 3518 patients diagnosed since 1959, followed to mid-2003. OUTCOME MEASURE: The outcome measure was standardized mortality ratio (SMR). RESULTS: A total of 461 deaths occurred. There was significantly raised mortality overall [SMR, 1.5; 95% confidence interval (CI), 1.4-1.7] and from most major causes of death including cardiovascular disease (SMR, 1.3; 95% CI, 1.1-1.5), nervous system disease (SMR, 2.8; 95% CI, 1.6-4.6), and respiratory disease (SMR, 2.3; 95% CI, 1.8-2.9). Mortality was particularly raised from diabetes (SMR, 5.8; 95% CI, 3.4-9.3), epilepsy (SMR, 7.2; 95% CI, 3.1-14.1), pulmonary embolism (SMR, 5.7; 95% CI, 2.5-11.3), peripheral vascular disease (SMR, 7.9; 95% CI, 2.9-17.2), vascular insufficiency of the intestine (SMR, 12.3; 95% CI, 4.0-28.8), renal disease (SMR, 5.0; 95% CI, 2.0-10.3), and femoral fracture (SMR, 39.4; 95% CI, 4.8-142.3). Mortality from ischemic heart disease was significantly decreased (SMR, 0.7; 95% CI, 0.5-0.9). CONCLUSIONS: Patients diagnosed with Klinefelter syndrome have raised mortality from several specific causes. This may reflect hormonal and genetic mechanisms.

Increased mortality in Klinefelter syndrome.

Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder in man and is a common cause of hypogonadism. To describe mortality in KS, we conducted an epidemiological study, using Danish registers covering the entire nation. We constructed a cohort of 781 Danish boys and men diagnosed with KS (from the Danish Cytogenetic Central Register) and a control group of 3803 men, matched by month and year of birth. Vital status was obtained from the Centralized Civil Register, and causes of death were obtained from the National Register of Causes of Death. We used Cox regression with stratification on groups of diagnoses according to International Classification of Diseases, 10th version. Where significant results were found, subsequent analyses were performed on subdivisions of diagnoses. We found that Klinefelter syndrome was associated with a significant increase in mortality risk of 40% (hazard ratio, 1.40; 95% confidence interval, 1.13-1.74), corresponding to a significantly reduced median survival of 2.1 yr. The increased mortality was mainly due to increased mortality from infectious, neurological, circulatory, pulmonary, and urinary tract diseases. Whether this increase is caused by the syndrome per se (i.e. hypogonadism) or other factors, e.g. socioeconomic, are involved is presently unknown.

Causes of death in X chromatin positive males (Klinefelter's syndrome).

The causes of death in 466 X chromatin positive males (Klinefelter's syndrome) studied prospectively over the last 25 years have been analysed. We have previously reported the overall mortality to be increased by 50% and life expectancy reduced by about five years. A highly significant increase in mortality from cerebrovascular disease was observed in the sub group considered to be most representative of X chromatin positive males in general. In the age group up to 45 years this increase could be attributed to deaths from subarachnoid haemorrhage. An increase in mortality from respiratory diseases was observed in those ascertained in psychiatric hospitals. In the sample as a whole there were small but highly significant numbers of deaths from carcinoma of the breast and aortic valve disease. The deaths from carcinoma of the breast were comparable with those expected if female mortality rates were applied.

Socioeconomic trajectories affect mortality in Klinefelter syndrome.

CONTEXT: Klinefelter syndrome (KS) is associated with male infertility, hypogonadism, and learning disability. Morbidity and mortality are increased and the causes behind remain unknown. Is it the chromosome aberration or is it caused by postulated poorer socioeconomic status? AIM: The aim of the study was to study the socioeconomic profile in KS and the impact of these factors on mortality. MATERIALS AND METHODS: This was a register study using Danish nationwide registries. One thousand forty-nine KS men and 100,824 controls were included. Information concerning cohabitation, fatherhoods, level of education, income, retirement, and death were obtained. Two hundred four KS and 14,725 controls died during the study period. For the socioeconomic parameters, median age at first relevant episode was calculated. Cohabitation, fatherhood, educational level, and retirement were analyzed using Cox regression, and income was analyzed using conditional logistic regression. Both analyses using each case and his matched controls as one stratum. RESULTS: KS men had significantly fewer partnerships [hazard ratio (HR) 0.66] and entered them later (median age 27.1 vs. 24.6 yr), fewer fatherhoods (HR 0.24),and they occurred later (median age 32.0 vs. 27.0 yr), lower educational level (HR 0.27), and lower income and were retired at an earlier age (43.5 vs. 60.3 yr). Mortality among KS men was significantly increased (HR 1.9), and after adjustment for cohabitation and educational status, mortality was still significantly increased (HR 1.5). CONCLUSION: A severely inferior outcome in all investigated socioeconomic parameters compared with the background population was present and mortality was increased and may partially be caused by the poorer socioeconomic status.

Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study.

BACKGROUND: Men with Klinefelter syndrome have one or more extra X chromosomes and have endocrine abnormalities. Case reports have led to suggestions that men with Klinefelter syndrome have elevated risks of several cancers, but published cohort studies have been relatively small. We conducted a nationwide cohort study to examine these risks. METHODS: We followed a cohort of 3518 men who had been cytogenetically diagnosed with Klinefelter syndrome in Britain from 1959 through 2002 and compared their cancer incidence and mortality with that of men in the national population. All statistical tests were two-sided. RESULTS: The standardized mortality ratio (SMR) for all cancers was 1.2 (95% confidence interval [CI] = 1.0 to 1.4). Compared with the general population, men with Klinefelter syndrome had higher mortality from lung cancer (SMR = 1.5, 95% CI = 1.0 to 2.0), breast cancer (SMR = 57.8, 95% CI = 18.8 to 135.0), and non-Hodgkin lymphoma (SMR = 3.5, 95% CI = 1.6 to 6.6) and lower mortality from prostate cancer (SMR = 0, 95% CI = 0 to 0.7). The standardized mortality ratios were particularly high for breast cancer among men with 47,XXY mosaicism (SMR = 222.8, 95% CI = 45.9 to 651.0) and for non-Hodgkin lymphoma among men with a 48,XXYY constitution (SMR = 36.7, 95% CI = 4.4 to 132.5). The cancer incidence data corroborated these associations. CONCLUSIONS: These results support a hormonal etiology for breast cancer in men and for prostate cancer and suggest that men with Klinefelter syndrome may be at substantially elevated risks for non-Hodgkin lymphoma, breast cancer, and, perhaps, lung cancer.

Mortality and cancer incidence in persons with numerical sex chromosome abnormalities: a cohort study.

Mortality and cancer incidence were assessed in a cohort of 1373 patients with numerical sex chromosome abnormalities diagnosed at three cytogenetics centres in Britain during 1959-90, and were compared with expectations from national rates. Four hundred patients with Turner's syndrome were followed, of whom 62 died, with a relative risk (RR) of death of 4.16 (95% confidence interval (CI) 3.22-5.39). Turner's syndrome patients had greatly raised risks of death from diseases of the nervous, cardiovascular, respiratory, digestive and genitourinary systems. One hundred and sixty three deaths occurred among 646 patients with Klinefelter's syndrome with a 47,XXY constitution, giving an RR of 1.63 (1.40-1.91). Mortality in these patients was significantly raised from diabetes and diseases of the cardiovascular, respiratory and digestive systems. There was also significantly increased mortality for patients with X polysomy (RR = 2.11 (1.43-3.02)) and Y polysomy (RR = 1.90 (1.20-2.85)), the former with significantly increased mortality from cardiovascular disease and the latter from respiratory disease. The only significantly raised risks of cancer incidence or mortality in the cohort were for lung cancer and breast cancer in patients with Klinefelter's syndrome with a 47,XXY constitution, and non-Hodgkin's lymphoma in men with more than three sex chromosomes.