XYY syndrome is a genetic condition found in males only. About 1 in 1, boys have it. Other symptoms can include problems with spoken language and processing spoken words, coordination problems, weaker muscles, hand tremors, and behavioral difficulties. Most boys with XYY syndrome can grow up healthy, have normal sexual development and fertility, and lead productive lives. Symptoms can vary greatly among boys. Depending on which symptoms a boy has and how severe they are, doctors may recommend various treatments.
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Metrics details. Sex chromosomal abnormalities are relatively common, yet many aspects of these syndromes remain unexplored. For instance epidemiological data in 47,XYY persons are still limited. Using a national Danish registry, we identified persons with 47,XYY or a compatible karyotype, whereof 36 were deceased; all were diagnosed from to We report nationwide prevalence data, data regarding age at diagnosis, as well as total and cause specific mortality data in these persons.
The average prevalence was Their median age at diagnosis was We found a significantly decreased lifespan from Total mortality was significantly increased compared to controls, with a hazard ratio of 3.
Dividing the causes of deaths according to the International Classification of Diseases, we identified an increased hazard ratio in all informative chapters, with a significantly increased ratio in cancer, pulmonary, neurological and unspecified diseases, and trauma.
We here present national epidemiological data regarding 47,XYY syndrome, including prevalence and mortality data, showing a significantly delay to diagnosis, reduced life expectancy and an increased total and cause specific mortality.
One of the first descriptions of 47,XYY is from by Jacobs et al [ 1 ]. Here a chromosome survey of male patients at the State Hospital in Carstairs was conducted. The hypothesis being that 47,XYY was particularly frequent among inmates in penal institutions.
Later, other studies took place in hospitals among consecutively born babies [ 2 — 7 ] using techniques enabling the identification of extra Y chromosome material. These studies identified highly variable number of 47,XYY persons, ranging in liveborn from 26 per , [ 2 ] to per , [ 4 ].
A few earlier chromosomal studies only used identification of Barr bodies, for instance from smears from the oral mucosa, hence no Y chromosome defects were identified [ 8 , 9 ]. By comparison, it is estimated that sex chromosomal abnormalities occur in 1 per births [ 10 ]. Only limited data regarding age at diagnosis in 47,XYY syndrome in a relatively unselected population are available [ 11 ].
To date, not much is generally known regarding clinical phenotype of individuals with 47,XYY , except tall stature [ 12 ], possibly due to the expression of three copies of the short statue homeobox-containing gene SHOX , which is located on the distal ends of Xp and Yp in the pseudoautosomal region 1 PAR1 [ 13 ]. One British study [ 14 ] identified a significantly increased mortality in total and in diseases of the respiratory system in a 47,XYY population compared to the background population.
However, to our knowledge nothing is known concerning prevalence and mortality in a nationwide identified 47,XYY population. We therefore undertook the present Danish nationwide study, investigating age at diagnosis, prevalence and mortality in a cohort of 47, XYY persons and comparing this to a large background population.
The Danish Cytogenetic Central Registry was founded in and contains all national data regarding the diagnoses of chromosomal anomalies, including information from the years before The first diagnosis of 47,XYY in Denmark was in Hereby index-persons were identified, for details see table 1.
It is important to emphasize that no information regarding phenotype or reasons for which the chromosomal analyses were performed were included in the registry. In and onwards, one unique ID-number was allocated to every living Dane. Date of birth and gender can easily be identified using the ID-number. Statistics Denmark was founded in , and contains numerous statistics regarding Denmark and Danes.
All controls were alive and living in Denmark on the date their index-person was diagnosed with 47,XYY. For two index-persons the matching was not undertaken for unknown reasons, and mortality data are therefore on 47,XYY persons.
Furthermore, we retrieved data regarding date of emigration, date of death, and up to three causes of death on these men. None were lost to follow-up. All controls were alive and registered in Denmark on the day the index-person was diagnosed with 47,XYY. Mortality data was updated with 31 st of December being the last date of death registered, whereas causes of death were updated until 31 st of December Thus, all who were deceased in and were registered with date of death, but without registration of causes of death.
Cause-specific mortality hazard ratios HR were calculated for each of the 19 chapters in ICD, as well as in total. The calculation of the expected prevalence was performed by adding all 47,XYY persons or variants identified in screening studies as well as the number of liveborn boys investigated. The confidence intervals were calculated using the poisson distribution.
To compare median age at diagnosis, median date of birth and median date of diagnosis in the three subgroups, we used the Kruskal-Wallis test. The time trend in age at diagnosis was analyzed using linear regression. The prevalence was calculated as number of diagnoses per liveborn boys in the background population per year of diagnosis. Confidence intervals were estimated using an approximation to the Poisson distribution.
The specific numbers of liveborn boys in the background population were obtained using Statistics Denmark. To identify changes in prevalence per year of diagnosis we used Poisson regression. The average prevalence was calculated as average number of incident 47,XYY persons during divided by the average number of liveborn boys in the background population during the same period.
This study period was applied to ensure enough run-in time in the Danish Cytogenetic Registry from time of establishment. Mortality was described with Kaplan-Meier survival estimates constructed using date of birth as entry.
Date of emigration, date of death or 31 st of December , whichever came first, were used as date of exit. For comparison log-rank analysis was applied.
HRs were calculated using Cox regression analysis with stratification, using each person and his matched controls as a stratum.
Hereby, comparisons were adjusted for age and calendar time, and calculation of expected number of deaths was possible. Time at risk was calculated as time from date of diagnosis until date of emigration, date of death or 31 st of December , whichever came first, this applied to both index-persons and controls. We made no formal corrections for multiple comparisons. We used Stata In the Danish Cytogenetic Central Registry we identified males diagnosed between and with 47,XYY or a compatible karyotype and divided them into three subgroups Table 1.
Age at diagnosis, year of birth and year of diagnosis is seen in Table 2. In all three subgroups age at diagnosis had a wide range, spanning more than 65 years. The distribution of age at diagnosis is seen in Figure 2. Twenty-five percent were diagnosed within the age of 5. Age at diagnosis in all males diagnosed in Denmark with 47,XYY during to During we identified 47,XYY persons, corresponding to an average of 4.
With an average of 32 liveborn boys in Denmark we thus identified Prevalence rate of 47,XYY males in Denmark during to The number of diagnosed 47,XYY males in Denmark during per , liveborn boys per year of diagnosis. In Statistics Denmark we identified 20 matched controls; a minimum of 82 controls were identified per index-person.
During the study period 1 controls and 36 index-persons died, whereof ten deaths were expected. Twenty-eight index-persons died in the 47,XYY subgroup, four in the mosaic subgroup and four in the subgroup of others. Time at risk, corresponding to time from date of diagnosis to date of exit, was 3 years in the index-persons and years in the controls.
The median age of survival was Kaplan-Meier survival graphs in 47,XYY compared to an age-matched male background population. Time at risk was calculated from date of birth until date of censoring see Materials and Methods for details. Solid line controls, and thin line persons. Number of persons and controls are indicated below the figure. Due to date of death in or later, the causes of deaths were not available in one 47,XYY person and in controls.
For another ten controls the date of death was before and without known cause of death. These ten deaths were only included in the analysis of total mortality. Using Cox regression we identified a significantly increased total mortality, with a HR of 3. The HRs of all informative chapters corresponding to chapters with at least one deceased person and one deceased control are shown in Figure 5.
Hazard ratios of total and cause specific mortality in 47,XYY compared to age-matched males. Time at risk was calculated from date of diagnosis until date of censoring see Materials and Methods for details. The causes are divided in nineteen chapters according to the International Classification of Diseases. Only informative chapters are included. Nationwide we have identified all males diagnosed with a diagnosis compatible with 47,XYY and identified a significantly increased total mortality.
Generally, cause specific mortality was increased compared to age and gender matched controls. Mortality data have to our knowledge not before been reported in a nationwide cohort with this specific karyotype. Our finding of a total mortality ratio of 3. The reduction of lifespan of In addition, we demonstrate a considerable delay in diagnosis and a low prevalence of 47,XYY. In all informative chapters cause specific mortality was generally increased.
Analyzing the chapters separately, we identified a significantly increased mortality in cancer, neurological, and pulmonary diseases, trauma and the chapter of unspecified diseases. Further, we identified a statistically significant HR in the chapters concerning the skin, urological diseases, and chromosomal disorders.
The British data showed a significantly increased mortality in pulmonary diseases only [ 14 ]. Time at risk is comparable in the British study 3 years and the present one 3 years , but the distribution of age at diagnosis cannot readily be extracted from the former study. However, our exact matching of index-persons and controls is methodologically superior. If a similar approach was possible in the British study, probably further significant chapters would have been identified.
We have no obvious explanation for the finding of significantly increased mortality in the various ICD chapters. However, it is noteworthy that the HR of the cardiovascular diseases reached 2.
Metrics details. Sex chromosomal abnormalities are relatively common, yet many aspects of these syndromes remain unexplored. For instance epidemiological data in 47,XYY persons are still limited. Using a national Danish registry, we identified persons with 47,XYY or a compatible karyotype, whereof 36 were deceased; all were diagnosed from to We report nationwide prevalence data, data regarding age at diagnosis, as well as total and cause specific mortality data in these persons. The average prevalence was
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly.
47, XYY syndrome