Chromosome abnormalities found among 34910 newborn children: results from a 13-year incidence study in Århus,Denmark

Summary As part of a larger prospective study of the influence of environmental factors on pregnancy, birth and the fetus, chromosome examinations have been made in 34910 newborn children in Århus over a 13-year period. Klinefelter's syndrome was found in 1 per 576 boys, XYY in 1 per 851 boys, triple-X in 1 per 947 girls and Turner's syndrome in 1 per 1893 girls. Other sex chromosome aberrations were found in 1 per 11637 children. The total incidence of sex chromosome abnormalities was 1 per 426 children or 2.34 per 1000. The most frequent autosomal abnormalities were that of Down's syndrome with 1 per 592 children, and reciprocal translocations with 1 per 712 children. The total incidence of autosomal abnormalities was 1 per 164 children. Chromosome abnormalities were found in 276 liveborn children and in 19 fetuses, who were aborted after prenatal chromosome examination. The combined incidence of sex chromosomal and autosomal abnormalities was 1 per 118 children or 8.45 per 1000 children.     

Aneuploidies, chromosome aberrations and dominant gene mutations detected in 113,913 consecutive newborn children in Mexico

Data on 113,913 liveborn children from a hospital in Guadalajara, Jalisco (Mexico), were analysed for birth defects (BD); mutation rates were calculated for sporadic aneuploidy, chromosome aberrations and dominant gene mutations. The results showed a general incidence of 13.92 BD cases per 1000 liveborns, of which 1.64% were chromosomal abnormalities, 1.50% were aneuploid, 0.14% were structural chromosome aberrations and 3.23% were dominant gene mutations. The mutation rates were 8.20 x 10(-4) chromosomal abnormalities, 7.5 x 10(-4) aneuploidies, 7.0 x 10(-5) chromosome aberrations and 1.61 x 10(-3) dominant gene mutations/gamete/generation, respectively. The lethality rate was 15.32% of the liveborns with BD. The described findings estimate the incidence of new human mutants detected at birth in a sample of the Mexican population. They show that the rate for some aneuploidies are similar to those found in other populations previously reported in the literature but the rates of chromosome and dominant gene mutations were different.     

Chromosome examination of newborn children

Summary The purpose of making chromosome investigations of newborn children as well as ethical problems in such studies and in follow-up studies of children with chromosome abnormalities is discussed, and a survey of 6 chromosome studies from a total of 47145 newborn children is presented.It is stressed that more chromosome studies of newborn children are needed for several reasons, but one of the main reasons is to study the development of children with different chromosome abnormalities, especially those with sex-chromosome abnormalities and compare them with controls.     

Sex ratio at birth in India, its relation to birth order, sex of previous children and use of indigenous medicine

Objective

Sex-ratio at birth in families with previous girls is worse than those with a boy. Our aim was to prospectively study in a large maternal and child unit sex-ratio against previous birth sex and use of traditional medicines for sex selection.

Main Outcome Measures

Sex-ratio among mothers in families with a previous girl and in those with a previous boy, prevalence of indigenous medicine use and sex-ratio in those using medicines for sex selection.

Results

Overall there were 806 girls to 1000 boys. The sex-ratio was 720∶1000 if there was one previous girl and 178∶1000 if there were two previous girls. In second children of families with a previous boy 1017 girls were born per 1000 boys. Sex-ratio in those with one previous girl, who were taking traditional medicines for sex selection, was 928∶1000.

Conclusion

Evidence from the second children clearly shows the sex-ratio is being manipulated by human interventions. More mothers with previous girls tend to use traditional medicines for sex selection, in their subsequent pregnancies. Those taking such medication do not seem to be helped according to expectations. They seem to rely on this method and so are less likely use more definitive methods like sex selective abortions. This is the first such prospective investigation of sex ratio in second children looked at against the sex of previous children. More studies are needed to confirm the findings.     

Molecular studies of parental origin and mosaicism in 45,X conceptuses

Summary The present report summarizes molecular studies of parental origin and sex chromosome mosaicism in forty-one 45,X conceptuses, consisting of 29 spontaneous abortions and 12 liveborn individuals with Turner syndrome. Our studies indicate that most 45,X conceptuses have a single, maternally derived X chromosome, regardless of whether the conceptus is liveborn or spontaneously aborted. In studies of mosaicism, our identification of X- and Y-chromosome mosaics among 45,X spontaneous abortions indicates that mosaicism does not ensure survival to term of 45,X fetuses. However, the incidence of sex chromosmome mosaicism is substantially higher in liveborn than in aborted 45,X conceptuses, indicating that the presence of a second cell line increases the likelihood of survival to term.     

A cytogenetic survey of mentally retarded children in Taiwan: final report on the incidence of chromosome abnormalities

A cytogenetic survey of 470 mentally retarded children from three different sources is reported. Thirty-eight patients (8.08%) were found to have recognizable chromosome abnormalities, including 4 cases of sex chromosomes and 34 cases of autosomes. The most prominent category of abnormality was trisomic 21, a total of 26 cases of this type was found in this study. Sex chromosome abnormalities contribute very little to the etiology of mental retardation. From the results of our three groups of patients as well as from those surveyed by others, it is concluded that the more severe the degree of mental retardation, the higher the incidence of chromosome abnormalities.     

Turner syndrome in adulthood

Turner syndrome is a common genetic disorder associated with abnormalities of the X chromosome and occurs in about 50 per 100,000 liveborn girls. It is associated with reduced adult height, gonadal dysgenesis and thus insufficient circulating levels of female sex steroids and infertility. Morbidity and mortality are increased throughout the lifespan. The average intellectual performance is within the normal range. A number of recent clinical studies have given new insight particularly into the adult phase of Turner syndrome. Treatment with growth hormone during childhood and adolescence enables a considerable gain in adult height. In most cases puberty has to be induced and female sex hormone replacement therapy is given during adulthood. Type 2 diabetes is often seen, and hypertension and associated cardiovascular disorders are frequent. The proper treatments of these disorders have not been firmly established. Since the risk of cardiovascular and endocrinological disease is clearly elevated, proper care during adulthood is crucial. Cognition and social functioning are altered in Turner syndrome.     

Frequency of chromosome variants in human populations]

Chromosome variants were analyzed in the course of the population chromosome investigation of 6000 newborns and clinical cytogenetic studies of 403 married couples with recurrent spontaneous abortions, stillbirths or offsprings having congenital malformations or Down's syndrome. The following variants were determined: 1) Igh+, 9gh+, 16gh+ - the enlargement of the secondary constrictions of the size, more than 1/4 of the long arm of the chromosome; 2) Dp+ or Gp+ - the enlargement of the short arms of acrocentrics, their size being more than the short arm of the chromosome 18; 3) Ds+ or Gs - large satellites of the acrocentrics which are equal or more than the thickness of the chromatids of the long arms; 4) Es+ - satellites on the short arms of the chromosomes 17 or 18; 5) Dss of Gss - double satellites; 6) Yq+ - the enlargement of the long arm of Y chromosome, the size of which being more than G chromosome; 7) Yq- - deletion of the long arm of Y chromosome, the size of the long arm being less than chromosomes 21--22. The total frequency of variants in newborns was 12.8/1000 births. The incidence of different types of variants per 1000 births was as follows: Igh+ - 0.33; 9gh+ - 0.17; 16gh+ - 0.50; Ds+ - 2.33; Dp+ - 1.50; Dp- - 0.17; Gs+ - 0.83; Gp+ - 2.17; Yq+ - 6.91/1000 males; Yg- - 0.99/1000 males; double variants - 0.33; other variants - 0.33. 4.0% of married couples with recurrent spontaneous abortions had major chromosome aberrations, 14.6% - extreme variants of chromosomes. Among 113 couples with the history of congenital malformations in their offsprings major chromosome abnormalities were found in 4.4%, chromosome variants - 13.3%. The frequency of chromosome variants among 139 patients with Down's syndrome was 7.2%. In one case Robertsonian translocation t(DqGa) was determined. The most frequent types of variant chromosomes were Ds+, Dp+, Es+, Yq+.     

Prevalence of Edwards' syndrome. Clustering and seasonal variation?

Summary The incidence of Edwards' syndrome was found to be 1 per 4857 newborn children of 34000 consecutively newborn children in two Danish counties. Six of the 7 cases were born during the months of February through April.The incidence was high compared with the expected incidence of Edwards' syndrome of approximately 1 per 10000. This might be due to clustering in the area studied during the period 1967 to 1973.The finding of variations in incidence of children with Edwards' syndrome in different parts of the world, as well as the finding of seasonal variation in birth of such children, indicates that some of the etiological factors of nondisjunction of chromosome 18 are of an environmental nature.     

Implications of the Hiroshima-Nagasaki genetic studies for the estimation of the human "doubling dose" of radiation

Since 1946 a continuous effort to evaluate the potential genetic effects of the atomic bombs has been sustained. Observations on children born in Hiroshima and Nagasaki include sex ratio, congenital malformations, stillbirths, survival of liveborn infants, chromosomal abnormalities (sex chromosomal abnormalities and balanced chromosomal rearrangements), mutations altering protein structure or activity, and physical growth and development. There are no statistically significant differences between the children of parents who received increased amounts of radiation at the time of the bombings and those whose parents did not. However, the difference between the two sets of children is consistent with the hypothesis of a genetic effect of the exposure, but its magnitude suggests humans are not as sensitive to the genetic effects of radiation as projected from the mouse paradigm.     

Frequency and distribution of chromosome abnormalities in human spermatozoa

This study reviews the frequency and distribution of numerical and structural chromosomal abnormalities in spermatozoa from normal men obtained by the human-hamster system and by multicolor-FISH analysis on decondensed sperm nuclei. Results from large sperm karyotyping series analyzed by chromosome banding techniques and results from multicolor FISH in sperm nuclei (of at least 10(4) spermatozoa per donor and per probe) were reviewed in order to establish baseline values of the sperm chromosome abnormalities in normal men. In karyotyping studies, the mean disomy frequency in human sperm is 0.03% for each of the autosomes, and 0.11% for the sex chromosomes, lower than those reported in sperm nuclei by FISH studies using a similar methodology (0.09% and 0.26%, respectively). Both types of studies coincide in that chromosome 21 and sex chromosomes have a greater tendency to suffer segregation errors than the rest of the autosomes. The mean incidence of diploidy, only available from multicolor FISH in sperm nuclei, is 0.19%. Inter-donor differences observed for disomy and diploidy frequencies among FISH studies of decondensed sperm nuclei using a similar methodology could reflect real differences among normal men, but they could also reflect the subjective application of the scoring criteria among laboratories. The mean frequency of structural aberrations in sperm karyotypes is 6.6%, including all chromosome types of abnormalities. Chromosome 9 shows a high susceptibility to be broken and 50% of the breakpoints are located in 9q, between the centromere and the 9qh+ region. Structural chromosome aberrations for chromosomes 1 and 9 have also been analyzed in human sperm nuclei by multicolor FISH. Unfortunately, this assay does not allow to determine the specific type of structural aberrations observed in sperm nuclei. An association between advancing donor age and increased frequency of numerical and structural chromosome abnormalities has been reported in spermatozoa of normal men.     

Incidence of chromosome abnormalities in newborn children. Comparison between incidences in 1969–1974 and 1980–1982 in the same area

Summary As part of an ongoing study of the influence of environmental factors on pregnancy, childbirth, and fetuses, comparisons have been made between incidences in 1969–1974 and in 1980–1982 of chromosome aberrations in liverborn children in the same area of Denmark. The incidence of chromosome aberrations in the first period was 2.6 per 1000, compared with 4.1 per 1000 during the latter period. However, the difference was mainly due to an increase in inversions, and this in turn was due to a difference in chromosome staining methods between the two periods.It is concluded that the Danish study and similar studies in the United States, Canada, and Scotland indicate that early detection of chromosome aberrations by chromosome examination at birth is indicated in order to be able to inform and counsel parents of children with chromosome aberrations. Chromosome examination at birth is also of importance in the diagnosis of structural inheritable chromosome aberrations and consequent family investigation and genetic counseling.     

Autosomal reciprocal translocations in newborn children and their relatives

Summary In an incidence study of chromosome abnormalities among 5049 consecutive liveborn children at a Danish maternity hospital we found 43 with major chromosome abnormalities; 7 had a balanced reciprocal autosomal translocation. Segregation rate in the families of the 6 cases, who were inherited, showed no significant deviation from unity between carriers of balanced translocations and individuals with normal chromosome constitution. The sex distribution of carriers and those with normal chromosome constitution was normal, and segregation and distribution between carriers and non-carriers was independent of whether the carrier was a male or a female.No relatives with the unbalanced form of the translocations were found in the 6 families studied, but there was a significant increase of stillborns and children, who died during the first week of life, among carriers of the translocation compared with near relatives with a normal chromosome constitution as well as with all children born in the hospital, where they were found, and in the Danish population. The frequency of abortions was higher among the carriers than among the individuals with normal karyotypes. When the figures of stillborn children, children who died during the first week of life as well as spontaneous abortions were added to those who lived, we found that the average number of pregnancies per family was the same in carriers as in their relatives with normal chromosomes. Children with presumptive unbalanced form of translocations thus seem to have ended up as abortions, stillborns or children, who died during their first week of life.None of the probands or their relatives with reciprocal translocations had physical or mental abnormalities which could be associated with the translocation. There was no obvious difference in the physical and mental appearance or health between carriers and relatives with normal chromosome constitutions. Reciprocal autosomal translocations do not seem to have any deleterious effect on mental or physical development.

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Zusammenfassung In einer Untersuchung über Chromosomenanomalien bei 5049 auslesefrei gewonnenen Neugeborenen einer dänischen Entbindungsklinik wurden 43 mit gröberen Anomalien der Chromosomen gefunden; 7 hatten eine balancierte autosomale reziproke Translokation. Eine Untersuchung der Aufspaltung zwischen Trägern balancierter Translokationen und Personen mit normalem Karyotyp zeigte in den 6 Familien, in denen die Translokation ererbt war, keine signifikante Abweichung von der Gleichverteilung. Auch das Geschlechtsverhältnis zwischen Überträgern und Normalen weicht nicht von der Erwartung ab. Die Überträgereigenschaft war vom Geschlecht unabhängig. In den 6 untersuchten Familien fanden sich keine Verwandten mit der unbalancierten Form der Translokation; jedoch war die Zahl der Totgeburten sowie der Kinder, die in der 1. Lebenswoche starben, signifikant erhöht bei den Trägern der Translokation im Vergleich mit nahen Verwandten mit normalem Karyotyp sowie mit den im gleichen Hospital geborenen Kindern und der dänischen Gesamtbevölkerung. Bei den Überträgern war auch die Abortrate höher als bei Personen mit normalem Karyotyp. Wenn man die Zahl der Totgeburten, der Todesfälle der 1. Lebenswoche sowie der spontanen Aborte zu den lebenden hinzuzählt, so erwies sich die durchschnittliche Zahl der Schwangerschaften/Familie in den Überträgerfamilien als gleich hoch wie bei den Verwandten mit normalem Karyotyp. Es sieht also so aus, als ob Früchte mit unbalancierten Translokationen als Aborte, Totgeburten und Todesfälle in der 1. Lebenswoche geendet wären.Keiner der Probanden oder ihrer Verwandten mit reziproker Translokation hatte physische oder geistige Anomalien, die auf die Translokation zurückgeführt werden konnten, und es fand sich kein physischer, geistiger oder geburtsbedingter Unterschied zwischen Überträgern und Verwandten mit normalen Chromosomen. Demnach haben autosomale reziproke Translokationen offenbar keinen schädlichen Effekt auf die geistige oder körperliche Entwicklung.

     

Chromosome studies in a neonatal population

The results of chromosome studies on 6809 consecutive newborn infants are presented. One hundred and one (1.48%) were heterozygous for a marker chromosome, the significance of which is not at present clear. Twenty-two infants (0.32%) had a major chromosome abnormality. Only six of these infants (0.09%) had a clinically recognizable abnormal phenotype (Down''s syndrome). The occult chromosome abnormalities included five sex chromosome abnormalities (one 47,XYY; two 47,XXY; two 47,XXX) and 11 balanced translocations. Seven of these were t(DqDq) and four were reciprocal translocations. The results of the present survey are combined with four other similar neonatal surveys in which a total of 23,328 newborns have been screened. Of these, 117 (0.5%; range 0.65-0.32%) had major chromosome abnormalities. The majority of these (72.7%) would not have been detected at birth without chromosome studies, an important fact in the context of prenatal diagnosis of chromosome disease and the early ascertainment of high-risk families.     

Epidemiology of rheumatic heart disease in black shcoolchildren of Soweto,Johannesburg.

A survey to determine the prevalence of rheumatic heart disease (R.H.D.) in Black children was conducted in the creeches and primary schools of the South Western Townships of Johannesburg (Soweto). A total of 12 050 Black children were examined by 10 cardiologists in May to October 1972. The overal prevalence rate of R.H.D. was 6.9 per 1000, with a peak rate of 19.2 per 1000 in children of the seventh school grade. The maximal age incidence was 15-18 years and there was a female preponderance of 1 6:1. A rise in prevalence occurred with increasing family size. Most children (92%) were asymptomatic, and in 82.5% R.H.D. was diagnosed for the first time during the school survey. The commonest valve lesion was mitral regurgitation, which was present in 93% and occurred as an isolated lesion in 47.5%. Lancefield''s group A beta-haemolytic streptococcus was isolated from the throats of 52 per 1000 Soweto children. The auscultatory features of a non-ejection systolic click and late systolic murmur were prevalent (13.9 per 1000) and had several epidemiological factors in common with R.H.D. A comprehensive preventative campaign is urgently needed in South Africa, directed at both primary and secondary prophylaxis of R.H.D. The socioeconomic status of the community must be improved if optimal prevention is to be achieved.     

Aneuploidy in human spermatozoa

We reviewed the frequency and distribution of disomy in spermatozoa obtained by multicolor-FISH analysis on decondensed sperm nuclei in (a) healthy men, (b) fathers of aneuploid offspring of paternal origin and (c) individuals with Klinefelter syndrome and XYY males. In series of healthy men, disomy per autosome is approximately 0.1% but may range from 0.03 (chromosome 8) to 0.47 (chromosome 22). The great majority of authors find that chromosome 21 (0.18%) and the sex chromosomes (0.27%) have significantly elevated frequencies of disomy although these findings are not universal. The total disomy in FISH studies is 2.26% and the estimated aneuploidy (2× disomy) is 4.5%, more than double that seen in sperm karyotypes (1.8%). Increased disomy levels of low orders of magnitude have been reported in spermatozoa of some normal men (stable variants) and in men who have fathered children with Down, Turner and Klinefelter syndromes. These findings suggest that men with a moderately elevated aneuploidy rate may be at a higher risk of fathering paternally derived aneuploid pregnancies. Among lifestyle factors, smoking, alcohol and caffeine have been studied extensively but the compounding effects of the 3 are difficult to separate because they are common lifestyle behaviors. Increases in sex chromosome abnormalities, some autosomal disomies, and in the number of diploid spermatozoa are general features in 47,XXY and 47,XYY males. Aneuploidy of the sex chromosomes is more frequent than aneuploidy of any of the autosomes not only in normal control individuals, but also in patients with sex chromosome abnormalities and fathers of paternally derived Klinefelter, Turner and Down syndromes.     

Paracentric inversion of chromosome 15(q15q24): description of three families

Three unrelated families with paracentric inversion of chromosome 15(q15q24) are reported. An additional pericentric inversion of chromosome 9 with breakpoints in p11.2q13 was also observed in one of the three families. Reproductive problems, such as stillbirths, spontaneous abortions and two live-born children with multiple abnormalities, were present.     

Ethical considerations regarding parental decisions for termination following prenatal diagnosis of sex chromosome abnormalities

Termination rates following prenatal diagnosis of sex chromosome abnormalities have been reported to be in a very wide spectrum (12.7-86.5%) in various studies. The different attitudes in management of prenatal diagnosed sex chromosome abnormalities may depend on several factors as the type of the abnormality, the indication for prenatal testing, the number of previous healthy children and whether the pregnancy was assisted or spontaneous. In the current study, we look at prenatal diagnostic procedures carried out in our department over a period of 5 years (2002-2007). We did not detect sex chromosome abnormalities in the 43 cordocenteses and the 26 chorionic villus samples. Among the 1130 amniocentesis patients, 12 cases (1.06%) were diagnosed as having sex chromosome abnormalities. Five (41.67%) of 12 pregnancies with sex chromosome abnormalities were terminated (one case with 47,XXY, one case with 46,X,del(X), and three cases with 45,X karyotype); whereas seven pregnancies (58.33%) continued. Among the factors influencing parents' decision-making, the attitude of the health-care professional giving the post-diagnosis counseling seems to be the most important, next to the socio-economic and educational status of the parents.     

Incidence and outcome of symptomatic urinary tract infection in children.

The incidence of symptomatic urinary tract infection in 2879 children aged under 15 years was studied over 18 months in a single general practice. Infection was diagnosed if bacterial counts in three consecutive samples exceeded 100,000/ml. The incidence of urinary tract infection was 1.7 per 1000 boys at risk per year and 3.1 per 1000 girls. These values are lower than those of comparable studies, possibly because of the stricter diagnostic criterion used in the study. Urinary pus cell counts were also carried out and sometimes found to be misleading. Of the 14 children found to have an infection, three had a radiological abnormality. Five of the children had a recurrence of infection within the first two years, and one an asymptomatic bacteriuria seven years after diagnosis. Only six out of 34 children presenting with dysuria had infected urine, and an association was discovered between abacterial dysuria (or the urethral syndrome) in the remainder and a concurrent upper respiratory tract infection. All children should undergo radiological investigation after their first confirmed infection. Diagnosis and management could be improved by providing all general practitioners with a semiquantitative method of urine culture such as the dip slide.     

Immunological Abnormalities in Juvenile Myelomonocytic Leukaemia

Immunological studies were performed on 24 children suffering from juvenile myelomonocytic leukaemia. Strikingly high serum immunoglobulin levels with a frequent tendency towards homogeneity and light-chain imbalance were present, together with a high incidence of antinuclear antibodies (52%) and antihuman IgG antibodies (43%). Members of the families of 19 of the children were also studied. A few similar abnormalities were found in eight families, mostly clustered in four of them. The significance of the association of these immunological aberrations with juvenile myelomonocytic leukaemia is at present unknown. In view of the interrelation observed in experimental models between immunological abnormalities and oncogenic viruses the possibility of a common aetiological factor such as a viral infection during fetal life is suggested.