Down syndrome rates and relaxed selection at older maternal ages.

Preferential survival in older mothers of fetuses with Down syndrome has been proposed as contributing to the maternal-age effect of this condition. If correct, this provocative hypothesis, which may be termed "relaxed selection," has major implications for approaches to prevention of Down syndrome live births in older women. Several predictions of this hypothesis are examined here by comparisons of parental ages among various populations. These revealed that: (1) mean maternal age of Down syndrome live births is slightly lower than that of Down syndrome spontaneous fetal deaths; (2) mean maternal age of those with mutant D/21 translocation Down syndrome is about the same as that of controls; (3) the ages of Down syndrome mothers who have Down syndrome live births is slightly lower than ages of Down syndrome mothers who have unaffected live births; and (4) in recent data on 47, +21 cases in which the extra chromosome 21 is of paternal origin, the mean maternal ages are 4-5 years lower than the maternal ages of cases of maternal origin (in contrast to earlier reports). All of these observations are contrary to the hypothesis that relaxed selection contributes significantly to the maternal-age association of Down syndrome. If there is any effect of relaxed selection, it is likely to be very weak and/or act primarily upon abortions that occur before recognition of pregnancy.     

Maternal fever and neural tube defects

It has been proposed that hyperthermia in the pregnant woman is associated with neural tube defects in her offspring. We analyzed retrospective interview data for a maternal history of probable febrile illness during the first trimester of pregnancy among mothers of infants with anencephaly or spina bifida. There were two control groups--mothers of infants with Down syndrome and mothers of infants with cleft lip or palate. With the Down syndrome group serving as controls, the incidence of febrile illness among mothers of all infants with neural tube defects was significantly elevated. With the cleft group as controls, the fever incidence was not significantly increased in the neural tube defect groups. When the combined cleft and Down syndrome controls were used, only mothers of the spina bifida group had an elevated fever incidence. Epidemiology data suggest an association of maternal fever during pregnancy with neural tube defects in the offspring.     

Effects of Low Doses of Fluoride on Serum Proteins and a Serum Enzyme in Man

FLUORIDE ions have long been known to exert an inhibitory effect on the activity of certain enzymes-Frajola¹ lists ten human enzymes which are definitely inhibited in vitro and suggests that there may be more. In an experiment in one subject receiving 36 mg of sodium fluoride daily for 18 days Frajola was able to show that the activities of the serum enzymes lactic dehydrogenase, acid phosphatase and glutamic transaminase were reduced, but he does not say whether the general health of the subject was affected. Opponents of fluoridation as a public health measure argue that the action as an enzyme inhibitor will affect general health and they quote instances of subjectively assessed ill-health and allergylike reactions following fluoridation of public water supplies, but careful medical observations in fluoridated areas have shown no increase of systemic disease and no significant variation in mortality rates. It has been stated² that there is no evidence that fluoride ingested at 1 p.p.m. in drinking water has any effect on human enzyme activity, but there are no specific experimental data on this question.     

The effect of a pattern in palmar interdigital II on a-b ridge count in black and white Down syndrome cases and controls

An unconfirmed study by Fang (Ph.D. thesis, Univ. of London, 1950) in Britain showed that individuals with Down syndrome had lower total a-b ridge counts in palmar Interdigital area II (ID II) than a group of controls. This study compares 603 white Down syndrome cases and 93 black Down syndrome cases with 668 white and 402 black controls. Our results confirm those of Fang in that the Down syndrome cases in both racial groups had lower total a-b ridge counts than their respective controls. In addition, the black controls and Down syndrome cases had lower a-b ridge counts than their white counterparts. The mean a-b ridge count was significantly lower in individuals with a pattern in ID II compared to individuals without a pattern in ID II in both the Down syndrome and control groups. Some of the lower a-b ridge counts in the Down syndrome samples can be accounted for by the fact that there is an increased frequency of a pattern in ID II in Down syndrome cases. Both Down syndrome and normal individuals who had a pattern unilaterally had a lower than expected a-b ridge count on the contralateral hand that did not have a pattern. There was a tendency also for increased asymmetry in Down syndrome cases with a pattern in ID II.     

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project

BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population‐based case‐control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08–2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11–2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85–1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Molecular changes in fetal Down syndrome brain

Trisomy of human chromosome 21 is a major cause of mental retardation and other phenotypic abnormalities collectively known as Down syndrome. Down syndrome is associated with developmental failure followed by processes of neurodegeneration that are known to supervene later in life. Despite a widespread interest in Down syndrome, the cause of developmental failure is unclear. The brain of a child with Down syndrome develops differently from that of a normal one, although characteristic morphological differences have not been noted in prenatal life. On the other hand, a review of the existing literature indicates that there are a series of biochemical alterations occurring in fetal Down syndrome brain that could serve as substrate for morphological changes. We propose that these biochemical alterations represent and/or precede morphological changes. This review attempts to dissect these molecular changes and to explain how they may lead to mental retardation.     

Hypochondroplasia due to FGFR3 gene mutation (N540K) and mosaic form of Down syndrome in the same patient

The simultaneous presence of Down syndrome and achondroplasia has rarely been reported in the literature, and our search revealed only six patients with such an association. We are reporting the first case of a patient with Down syndrome and hypochondroplasia. In this patient, Down syndrome was clinically recognised and confirmed by the cytogenetic finding of mosaic karyotype (47,XX,+21/46,XX) shortly after birth. She was subsequently diagnosed with hypochondroplasia at the age of 6 years when disproportional short stature, stocky habitus and macrocephaly were observed. These phenotypic findings were later confirmed by the presence of fibroblast growth factor receptor 3 (FGFR3) gene mutation N540K. The overlapping common clinical features of Down syndrome and hypochondroplasia resulted in delayed diagnosis of hypochondroplasia in our patient and the associated deleterious effect on her linear growth. Her final height is 126.5 cm, which is −3.76 standard deviations (SD) lower than the median height in patients with Down syndrome, and is under the lower borderline of the adult height range for women with hypochondroplasia.     

BDNF and DYRK1A Are Variable and Inversely Correlated in Lymphoblastoid Cell Lines from Down Syndrome Patients

Down syndrome or trisomy 21 is the most common genetic disorder leading to mental retardation. One feature is impaired short- and long-term spatial memory, which has been linked to altered brain-derived neurotrophic factor (BDNF) levels. Mouse models of Down syndrome have been used to assess neurotrophin levels, and reduced BDNF has been demonstrated in brains of adult transgenic mice overexpressing Dyrk1a, a candidate gene for Down syndrome phenotypes. Given the link between DYRK1A overexpression and BDNF reduction in mice, we sought to assess a similar association in humans with Down syndrome. To determine the effect of DYRK1A overexpression on BDNF in the genomic context of both complete trisomy 21 and partial trisomy 21, we used lymphoblastoid cell lines from patients with complete aneuploidy of human chromosome 21 (three copies of DYRK1A) and from patients with partial aneuploidy having either two or three copies of DYRK1A. Decreased BDNF levels were found in lymphoblastoid cell lines from individuals with complete aneuploidy as well as those with partial aneuploidies conferring three DYRK1A alleles. In contrast, lymphoblastoid cell lines from individuals with partial trisomy 21 having only two DYRK1A copies displayed increased BDNF levels. A negative correlation was also detected between BDNF and DYRK1A levels in lymphoblastoid cell lines with complete aneuploidy of human chromosome 21. This finding indicates an upward regulatory role of DYRK1A expression on BDNF levels in lymphoblastoid cell lines and emphasizes the role of genetic variants associated with psychiatric disorders.     

Down syndrome and the genes of human chromosome 21: current knowledge and future potentials. Report on the Expert workshop on the biology of chromosome 21 genes: towards gene-phenotype correlations in Down syndrome. Washington D.C., September 28-October 1, 2007

Down syndrome (DS), trisomy of human chromosome 21, is the most common genetic cause of intellectual disability. With an incidence in some countries as high as one in approximately 700 live births, and a complex, extensive and variably severe phenotype, Down syndrome is a significant medical and social challenge. In recent years, there has been a rapid increase in information on the functions of the genes of human chromosome 21, as well as in techniques and resources for their analysis. A recent workshop brought together experts on the molecular biology of Down syndrome and chromosome 21 with interested researchers in other fields to discuss advances and potentials for generating gene-phenotype correlations. An additional goal of the workshop was to work towards identification of targets for therapeutics that will correct features of DS. A knowledge-based approach to therapeutics also requires the correlation of chromosome 21 gene function with phenotypic features.     

Water fluoridation,tooth decay in 5 year olds,and social deprivation measured by the Jarman score: analysis of data from British dental surveys.

OBJECTIVE: To examine the effect of water fluoridation, both artificial and natural, on dental decay, after socioeconomic deprivation was controlled for. DESIGN: Ecological study based on results from the NHS dental surveys in 5 year olds in 1991-2 and 1993-4 and Jarman underprivileged area scores from the 1991 census. SETTING: Electoral wards in three areas: Hartlepool (naturally fluoridated), Newcastle and North Tyneside (fluoridated), and Salford and Trafford (non-fluoridated). SUBJECTS: 5 year old children (n = 10,004). INTERVENTION: Water fluoridation (artificial and occurring naturally). MAIN OUTCOME MEASURE: Ward tooth decay score (score on the "decayed, missing, and filled tooth index" for each electoral ward). RESULTS: Multiple linear regression showed a significant interaction between Jarman score for ward, mean number of teeth affected by decay, and both types of water fluoridation. This confirms that the more deprived an area, the greater benefit derived from fluoridation, whether natural or artificial (R2 = 0.84, P < 0.001). At a Jarman score of zero (national mean score) there was a predicted 44% reduction in decay in fluoridated areas, increasing to a 54% reduction in wards with a Jarman score of 40 (very deprived). The area with natural fluoridation (at a level of 1.2 parts per million-higher than levels in artificially fluoridated areas) had a 66% reduction in decay, with a 74% reduction in wards with a Jarman score of 40. CONCLUSION: Tooth decay is confirmed as a disease associated with social deprivation, and the more socially deprived areas benefit more from fluoridation. Widespread water fluoridation is urgently needed to reduce the "dental health divide" by improving the dental health of the poorer people in Britain.     

Onychomycosis in Children with Down Syndrome

Purpose of Review

Fungal infection of the nail, known as onychomycosis, occurs more frequently in older age, showing a higher prevalence in pediatric age in recent years. A high rate of dermatological infections befalls in patients with Down syndrome, including onychomycosis, due to a decrease in T and B lymphocytes in number and function, resulting in a disarrangement of cellular and humoral immunity. This has led to several investigations on onychomycosis in children with Down syndrome, so the purpose of this review is to show the available evidence.

Recent Findings

The etiological agents of onychomycosis can be dermatophytes, non-dermatophyte molds, and yeasts. Most cases are related with dermatophytes; Trichophyton rubrum being the most common cause. In children with Down syndrome, T. rubrum has been reported as the main cause, followed by T. mentagrophytes. Distal lateral subungual onychomycosis is the most common variety of onychomycosis in children. The importance of identifying the fungus lies in selecting the appropriate treatment, since not all antifungals have the same spectrum of action against molds and Candida. Terbinafine has showed to be safe and effective for the treatment of onychomycosis in patients from special populations, including children with Down syndrome. In patients with Down syndrome, treatment for onychomycosis has not been completely studied; so far, terbinafine has shown the best results.

Summary

The clinical presentations of children with Down syndrome and the rest of the general pediatric population are similar. However, there are few studies about onychomycosis in children with Down syndrome. It is necessary to perform new onychomycosis research in this study population, in order to establish recommendations.

     

Growth curves of children with Down syndrome.

Growth curves of 105 children with Down syndrome (50 boys and 55 girls) were established. At birth height, weight and head circumference of Down syndrome children were lower than these parameters in controls. This delay remained stable until puberty. For weight there was no clear-cut pubertal growth spurt. For stature, the prepubertal growth spurt occurred earlier (at the age of 11 years in boys and 9 1/2 years in girls) than in controls but was less marked. As a result, Down syndrome patients had a short stature with a quite normal weight. These reference curves, available since prenatal diagnosis of Down syndrome is performed routinely, are helpful for monitoring normal and abnormal development in Down syndrome patients.     

Prenatal diagnosis, pregnancy terminations and prevalence of Down syndrome in Atlanta

BACKGROUND: The impact of prenatal diagnosis on the live birth prevalence of Down syndrome (trisomy 21) has been described. This study examines the prevalence of Down syndrome before (1990-1993) and after inclusion of prenatally diagnosed cases (1994-1999) in a population-based registry of birth defects in metropolitan Atlanta. METHODS: We identified infants and spontaneous fetal deaths with Down syndrome (n = 387), and pregnancies electively terminated after a prenatal diagnosis of Down syndrome (n = 139) from 1990 to 1999 among residents of metropolitan Atlanta from a population-based registry of birth defects, the Metropolitan Atlanta Congenital Defects Program (MACDP). Only diagnoses of full trisomy 21 were included. Denominator information on live births was derived from State of Georgia birth certificate data. We compared the prevalence of Down syndrome by calendar period (1990-1993, 1994-1999), maternal age (<35 years, 35+ years), and race/ethnicity (White, Black, other), using chi-square and Fisher's exact tests. RESULTS: During the period when case ascertainment was based only on hospitals (1990-1993), the prevalence of Down syndrome was 8.4 per 10,000 live births when pregnancy terminations were excluded and 8.8 per 10,000 when terminations were included. When case ascertainment also included perinatal offices (1994-1999), the prevalence of Down syndrome was 10.1 per 10,000 when terminations were excluded and 15.3 when terminations were included. During 1990-1993, the prevalence of Down syndrome was 24.7 per 10,000 among offspring to women 35+ years of age compared to 6.8 per 10,000 among offspring to women <35 years of age (rate ratio [RR] = 3.65, 95% confidence interval [CI] = 2.53-5.28). During 1994-1999, the prevalence of Down syndrome was 55.3 per 10,000 among offspring to women 35+ years compared to 8.5 per 10,000 among offspring to women <35 years (RR = 6.55, 95% CI = 5.36-7.99). There was no statistically significant variation in the prevalence of Down syndrome by race/ethnicity within maternal age and period of birth strata. During 1994-1999, the proportion of cases that were electively terminated was greater for women 35+ years compared to women <35 years (RR = 5.10, 95% CI = 3.14-8.28), and lower for Blacks compared to Whites among women 35+ years of age (RR = 0.33, 95% CI = 0.16-0.66). CONCLUSIONS: In recent years, perinatal offices have become an important source of cases of Down syndrome for MACDP, contributing at least 34% of cases among pregnancies in women 35+ years of age. Variation in the prevalence of Down syndrome by race/ethnicity, before or after inclusion of cases ascertained from perinatal offices, was not statistically significant. Among Down syndrome pregnancies in mothers 35+ years we found a lower proportion of elective termination among Black women compared to White women. We suggest that future reports on the prevalence of Down syndrome by race/ethnicity take into account possible variations in the frequency of prenatal diagnosis or elective termination by race/ethnicity.     

我国极端干旱天气变化趋势及其对城市水资源压力的影响

随着全球气候变化和水循环的改变,降水不均和持续干旱等极端天气事件的频度和强度增加,对水资源,尤其是人口和社会经济密度高的城市的水资源带来很大的影响和压力。为了探究我国干旱天气的变化趋势、区域特征、及其对城市水资源压力的影响,采用全国917个气象站点1951—2014年的逐日降水量数据集,分析了我国水资源及干旱的变化趋势和空间分布特征,并以我国289个主要地级市为研究对象,构建了气候变化情境下的城市基于区域降水禀赋的水资源压力评估方法,预测并展望了不同时段和不同代表性浓度路径(RCPs)情景下的未来城市水资源压力的情况。结果显示,我国极端干旱情况整体是随着全球气候变化增加的,年最长连续无降水天数变化速度的平均值为2.3d/100a,但是具有区域性,具体表现为南部地区干旱减缓而北部地区干旱严重。我国城市水资源压力受水资源禀赋的影响,呈现北方高而南方低的分布,除此之外水资源消耗大的大城市资源压力也比较大。随着气候变化,近期我国整体城市水资源压力相对现阶段增加了2%左右,具体水资源压力上升的城市有170个,水资源压力减少的城市有110个,剩下的9个城市水资源压力受气候变化的影响比较小。在低应对的RCP8.5情景下的城市水资源压力远远高于在RCP2.6情景,这说明减缓气候变化工作对降低我国城市水资源压力有积极作用;城市水资源压力的变化并不是均匀的,呈现南部减少而北部增加的变化趋势,我国华北地区城市的水资源压力最大,随着气候的变化,该地区的水资源压力也在随着时间不断增加,需要政府积极行动,提出有针对性和前瞻性的水资源规划方案,并依据方案采取措施,以应对气候变化造成的城市干旱增加。     

Social smiling in normal and down syndrome infants: A comparative study

The aim of this work has been to compare social smiling in Down syndrome (mongolism) and normal infants, attending especially to the brow movements that appear before it. Facial responses of eight Down syndrome and eight normal infants from three to five months were analized by means of an anatomically based measurement technique during face-to-face interactions with their mothers. Despite their mental retardation, Down syndrome infants showed identical muscle movements as normal infants before and during smiling. However, some differences were found in smile frequency and leght, as well as in the brow movements frequency before smiling. Results are discussed in terms of the psychophisiological dysfunction of Down syndrome infants that are originated by a chromosome imbalance.     

Epidemiology of congenital malformations in Gorno-Altaisk, Altai Republic, Russia

A retrospective epidemiological study has been performed using the data from healthcare institutions of the city of Gorno-Altaisk, Altai Republic, Russia for the period from 1983 to 2001. Congenital malformations (CMFs) have been studied in newborns, infants that died at ages under one year, and fetuses after 22 weeks of gestation. The most frequent malformations are those of the musculoskeletal and cardiovascular systems and multiple malformations, which account for 37.68, 18.22, and 8.9% of all congenital malformations, respectively. Their frequencies are 7.38, 3.57, and 1.74 per thousand, respectively. The frequency of congenital malformations subject to registration by the national system of CMF monitoring of the Russian Federation (21 malformation forms) is 6.08 per 1000 births and varies from 8.59 to 21.24. The frequency of the Down syndrome is 0.93 per 1000 births; it did not vary significantly during the period studied. The frequency of limb reduction deformities in the urban population of Altai Republic (0.32 per 1000 births) is higher than in other Siberian regions, including the cities of Kyzyl (Tyva Republic) and Tomsk and the Nyurba and Ust-Aldan uluses of Sakha Republic (Yakutia).     

Epidemiology of Down syndrome in South Australia, 1960-89.

During 1960-89 687 Down syndrome live births and 46 Down syndrome pregnancy terminations were identified in South Australia. Ascertainment was estimated to be virtually complete. The sex distribution of Down syndrome live births was found to be statistically different from the non-Down syndrome live-birth sex distribution (P less than .01). Smoothed maternal age-specific incidence was derived using both maternal age calculated to the nearest month and a discontinuous-slope regression model. The incidence of Down syndrome at birth for the study period was estimated to be 1.186 Down syndrome births/1,000 live births. Annual population incidence was shown to be correlated with trends in the maternal age distribution of confinements. If current trends in the maternal age distribution of confinements continue, the population incidence of Down syndrome in South Australia is predicted to exceed 1.5 Down syndrome births/1,000 live births during the 1990-94 quinquennium.