Genetic screening in Western Australia.

The wider application of genetic screening is described in four Western Australian populations. Counselling with prenatal diagnosis of Down's syndrome was offered to 57 women over the age of 35 years and less than 16 weeks' gestation who attended an antenatal outpatients department. Forty-four women consented to amniocentesis and two affected fetuses were found. Both public and private patients can be screened to detect fetuses with Down's syndrome. In a population of 200 pregnant girls whose infants were intended for adoption, a specially designed family history form aided identification of genetic disorders in 32 families. Counselling was offered to the biological parents, to the adoptive parents, and, prospectively, to the child in later years. The effectiveness of the family history as a screening device is illustrated in this adoption sample. Counselling of parents of 20 decreased malformed infants initiated the genetic counselling clinic in Western Australia and led to subsequent referral of 92 similar cases by the family doctors. It was found that parents who gave birth to malformed infants welcome information and risk figures. Diagnostic screening in a population of 6000 intellectually handicapped individuals yielded 1372 cases (23%) with Mendelian, multifactorial, or chromosomal modes of inheritance. This screening enabled patients with inherited causes for their intellectual handicap to be identified and placed on a register for health planning.     

Counselling about Down's syndrome: the parents' viewpoint.

The parents of 50 children with Down's syndrome were interviewed to find what sort of information they were given at the time of diagnosis and what arrangements were made for the child's future. Particular emphasis was placed upon the method and timing of giving the parents the diagnosis, the utilization of community resources to help the family and what information they would have liked to have been given in retrospect. The ages of the children ranged between three months and eight years at the time of the survey. Seventy-two per cent of parents were given the diagnosis during the first week, with an increasing proportion being dissatisfied with the timing the longer the delay in telling what was wrong with the child. The mother has been told first in 48% of cases, and both parents have been told together in only 20% of cases. Fifty-four per cent of parents were encouraged to take the baby home, 22% were encouraged to place the baby in an institution, while in 28% of cases the decision was left to them. Forty-six per cent of patients felt that an overly-pessimistic outlook had been given by the doctor. Eighty-four per cent had medical follow-up, community follow-up, or literature supplied, whereas 16% had no such arrangements made. The parents' own suggestions for better management were sought. The two most outstanding were to be placed in early contact with community facilities and to be given a chance to meet other parents of children with Down's syndrome.     

浅谈“唐氏综合征”

目的：降低“唐氏儿”出生率,提高我国人口出生质量。方法：分析其发病风险 发病机理、结局,特别是检测手段。结果：加强检测,可杜绝“唐氏儿”发生。结论：每位孕妇都应进行“唐氏儿”筛查。     

Philosophical medical ethics. Conclusion: the Arthur case revisited

Throughout his British Medical Journal series of 25 articles on medical ethics, Gillon frequently used the Arthur case (which involved a British physician who faced criminal charges for allowing a Down's syndrome newborn to die) to illustrate moral arguments concerning approaches to clinical dilemmas. He returns to the Arthur case in this essay on the obligations of physicians toward all patients with Down's syndrome. Gillon asks what implications one's view of the moral permissibility of allowing infants with this handicap to die has for the care of adults with the same condition. He concludes that the issue turns on the question of personhood, in particular that of newborns. If newborns are not accorded personhood status, then allowing those with severe handicaps to die may be justified but should not be considered morally different from actively killing them.     

Down's syndrome in South Australia.

In a survey of Down's syndrome in South Australia, 921 persons, both living and deceased, were identified; 717 individuals with the disorder were living in South Australia. Cytogenetic confirmation of the diagnosis had been made in 774 cases. From 1955 to 1977, the over-all incidence of Down's syndrome at birth was found to be 1.175/1000 live births. The incidence of Down's syndrome was significantly lower over the last five years of this period than for the first 18 years; thus it appears that the incidence of Down's syndrome in South Australia is falling. Analysis of maternal age changes with time has not revealed any changes to the maternal age-specific rates for Down's syndrome, although the rate for mothers aged 25 years or younger appears to be falling. The proportion of Down's syndrome babies born to women aged 35 years or more has decreased from 65.7% for those born before 1950 to 30.4% for those born from 1975 to 1977; similarly, the median maternal age has fallen from 37.12 years to 28.25 years. Regression analyses of maternal age rates for Down's syndrome by single years have produced figures suitable for genetic counselling. A plea is made that Down's syndrome should become a notifiable condition.     

Screening for Down's syndrome using serum alpha fetoprotein: a retrospective study indicating caution

A report was made on the outcome of a four year retrospective study in 27 064 pregnancies, of the clinical efficiency, sensitivity, and specificity of a screening programme for Down's syndrome based on reported strategies related to the measurement of maternal serum alpha fetoprotein. This study identified 27 pregnancies affected by Down's syndrome with a median multiple of the median maternal serum alpha fetoprotein concentration of 0.82. This figure is considerably higher than that obtained from previous reports on this subject. With an age related multiple of the median maternal serum alpha fetoprotein strategy, 30.8% of Down's affected pregnancies were identified as well as 11.6% of unaffected pregnancies. Perhaps a United Kingdom collaborative study should begin to investigate the reasons for such wide population variance in the reports for the median multiple of the median for Down's affected pregnancies. Until such studies are carried out, screening for Down's syndrome based on low maternal serum alpha fetoprotein concentration is premature.     

The prevention of Down's syndrome in the south western region of England 1975-1985

Cytogenetic prenatal screening for Down's syndrome in the South West Region of England from 1975 to 1985 was reviewed. The use of amniocentesis increased, and for the years 1981 to 1985 averaged 29.4% of women 35 years or over at their estimated date of delivery. 58 pregnancies were terminated after karyotyping of amniotic fluid cells confirmed trisomy 21. 385,440 live births were born in the region, 452 with Down's syndrome, giving a live birth incidence of 1 in 853. The effective impact of prenatal screening was calculated at an overall 8.3% reduction in Down's syndrome live births, but for the years 1981 to 1985 this rose to 11.3%. In spite of the introduction of new prenatal screening programmes that are not reliant solely on maternal age, it is predicted that substantial numbers of children with Down's syndrome are likely to be born each year. Adequate medical facilities will still be required for the survivors.     

Molecular diagnosis of Down’s syndrome

Objective To establish a new diagnostic method for Down’s syndrome using polymerase chain reaction (PCR).Methods DNA extracted from five healthy individuals and five Down’s syndrome patients was amplified in six specific tetranucleotide repeat loci on chromosome 21 using PCR. An accurate diagnosis was made by analyzing allelic distribution at each locus. Results All Down’s syndrome patients were identified as having at least two loci with three alleles, while none of the healthy individuals had three alleles. In addition, when two alleles were identified for a particular locus in the Down’s syndrome samples, it was more likely that the intensity ratio between the two alleles was close to 2∶1. Conclusion The molecular method can provide a fast, accurate, and economical alternation for the traditional cytogenetic diagnostic method for Down’s syndrome.     

Occipitofrontal-biparietal diameter ratio. An ultrasonic parameter for the antenatal evaluation of Down's syndrome.

The cephalic index of the fetal head was determined by the ultrasonic measurement of the occipitofrontal-biparietal diameter (OF-BPD) ratio in a pilot study of 53 patients at risk of Down's syndrome. The mean value of the OF-BPD ratio was 1.24, and a linear correlation between the occipitofrontal diameter (OFD) and the biparietal diameter (BPD) was observed. There was one case of Down's syndrome in this series. The fetal head was markedly brachycephalic with an OF-BPD ratio of 1.073. The results of this study suggest that when fetal brachycephaly is present, the probability of Down's syndrome is increased. Further evaluation of this parameter is warranted, as it is possible that this technique may provide a safe, and non-invasive method of screening the entire pregnant population for Down's syndrome.     

孕中期唐氏综合征血清学筛查的经济效益评价

目的 从临床及卫生经济学的角度探讨孕中期唐氏综合征产前筛查的意义.方法 采用酶联免疫吸附试验(ELISA)检测12 720名孕龄为14～20周的中国孕妇的血清甲胎蛋白(AFP)、绒毛膜促性腺激素(β-hCG)水平,结合孕妇的年龄、孕周等关键参数,计算唐氏综合征的风险系数,并对高危人群进行产前诊断.结果 761例唐氏综合征筛查高危妊娠妇女中,诊断唐氏综合征患儿7例;11 959例唐氏综合征筛查低危妊娠妇女中,诊断唐氏综合征2例.筛查成本为495 023元,安全指数为0.28.结论 采用ELISA法检测孕妇血清AFP和β-hCG的方法成本低、安全性高,是适合中国国情的唐氏综合征产前筛查方案.     

母血清生化二联、三联标记物筛查胎儿唐氏综合征

目的 用母血清生化标记物筛查胎儿唐氏综合征(Down’s syndrome,DS)等先天异常。方法 应用孕妇血清指标和时间分辨荧光免疫分析法对本院1996年11月-2001年3月在本科产前检查的2886例孕妇进行DS胎儿筛查。对高危孕妇作羊腹腔穿刺或早孕绒毛取材以得到胎儿染色体。对应用的指标捡出率及假阳性率进行分析。结果 共捡出11例DS,8例无脑儿;DS检出率3．8‰。结论 妊娠相关血浆蛋白A(PAPP-A)筛查胎儿DS有很好的价值并能使产前诊断时期提前,甲胎蛋白 游离人绒毛膜促性腺激素(AFP freeβ-HCG)可用于检测DS和胎儿异常。     

Incidence of Down's syndrome in a large Malaysian maternity hospital over an 18 month period

Over an 18 month period, 34,522 livebirths were delivered in the Maternity Hospital, Kuala Lumpur. 36 of them had Down's Syndrome. Based on our findings, the incidence of Down's syndrome among the Malaysian babies born in this hospital was 1:959 livebirths. According to racial distributions, the incidence among Malay was 1:981 livebirths, Chinese 1:940 livebirths, and Indian 1:860 livebirths. Our incidence was lower than those from the Western populations. Unlike others' studies, there was also a female preponderance of Down's syndrome among the Malaysian babies.     

High frequency of mitral valve prolapse and aortic regurgitation among asymptomatic adults with Down's syndrome

Although cardiac anomalies are well documented among children with Down's syndrome, data on the cardiac status of adults with Down's syndrome are sparse. Therefore, we performed cardiac auscultation and Doppler echocardiographic examinations in 35 asymptomatic adults with Down's syndrome. There were 25 men and ten women; their mean age (+/- SD) was 26 +/- 8 years. Only ten subjects (29%) had normal findings on examination. The most frequent abnormal findings were holosystolic mitral valve prolapse (MVP) in 20 subjects (57%) and mild aortic regurgitation in four subjects (11%). Of the 20 subjects with MVP, five had associated tricuspid valve prolapse, but none had notable mitral regurgitation. Thus, we found that the majority of asymptomatic adults with Down's syndrome had valvular heart abnormalities. The high frequency of MVP and aortic regurgitation suggests that these lesions may be specifically associated with Down's syndrome in adults.     

The Management of the Retarded Child in Practice

The management of the retarded child in general practice is discussed. The necessity of a thorough medical and psychological assessment is stressed. The problem of the parents is described from the point of view of the emotional stages through which they pass and the defence mechanisms they commonly use. The factors involved in planning the future program for the retarded child are enumerated and depend on the degree of mental and physical handicap, the socio-economic and emotional climate of the family and the available services in the area. Since a large proportion of retarded children remain at home, a systematic follow-up program by the practising physician should be encouraged.     

Neonatal duodenal obstruction with emphasis on cases with Down''s syndrome

In the past 31 years, 47 cases of duodenal obstruction were admitted to the Royal Belfast Hospital for Sick Children. Thirty-six per cent of these had Down's syndrome. The crude mortality was 48% but this figure was reduced to 33% in the last five years of the study. The combination of duodenal obstruction, Down's syndrome and any other abnormality carried an 89% risk of mortality.     

Consanguinity, non-disjunction, parental age and Down's syndrome

The effect of consanguinity on the non-disjunction mechanism in Down's syndrome, was examined in 417 cytogenetically confirmed Down's syndrome patients. The incidence of parental and grandparental consanguinity was 17.5% (n = 73), while that of only parental consanguinity was 17.2% (n = 71). First cousin marriages occurred more frequently, than uncle-niece and 2nd cousin marriages. With regard to parental age, only the mean age difference between consanguineous couples significantly differed from non-consanguineous couples. The inbreeding coefficient did not differ between trisomy 21 and translocation Down's families. From this study, it is concluded that consanguinity does not predispose to Down's syndrome.     

An introduction to philosophical medical ethics: the Arthur case

The application of moral theory to decisions involving medical ethics is illustrated by the 1981 case in which a British pediatrician, Dr. Leonard Arthur, was acquitted of attempted murder for prescribing dihydrocodeine and "nursing care only" for a Down's syndrome newborn after the child had been rejected by his mother. Gillon outlines the moral arguments of the "prosecution" and the "defense," and then categorizes their various premises in accordance with concepts of normative ethical theory.     

孕妇血清标记物在中孕筛查中的应用

目的 :通过对孕妇血清标记物甲胎蛋白 (AFP)和人绒毛膜促性腺激素 ( β -HCG )测定来筛选缺陷儿。 方法 :用放射免疫法对 6 2例孕 14～ 2 3周妊娠妇女上述标记物连测 3次 ,每次隔 12～ 14d ,以两次异常为高危个体。每例筛查者跟踪至胎儿出生后。结果 :在筛查中发现了 1例先天愚型和 1例无脑儿。结论 :上述两种血清标记物可以作为神经管缺陷和先天愚型筛查的一项常规方法     

二代测序技术在Cardio-facio-cutaneous综合征诊断中的应用研究

目的 探讨二代测序技术在辅助诊断RAS心肌病群的作用.方法 提取1例疑似Noonan综合征患儿及其父母外周血,采用aCGH、二代测序技术检测基因突变,并用Sanger法进行验证.结果 二代测序结果显示,患儿BRAF基因存在c. 1406G>A杂合突变.患儿一代测序结果与二代测序结果一致,父母一代测序结果显示该位点均为G/G野生型.结论 该患儿为CFC患者,二代测序技术在RAS心肌病群的鉴别诊断中可以起到很好的辅助作用.     

唐氏综合征筛查指标MoM值的正态性研究

目的: 考察江苏唐氏综合征产前筛查指标AFP和HCG的MoM值的正态性,探索Johnson分布体系中的SL分布族在上述指标正态性转换中应用的可行性和有效性. 方法: 资料来自于江苏省出生缺陷干预项目研究,采用对数正态和Johnson分布体系中的SL正态性转换方法. 结果: 两指标的MoM值均不服从正态分布;对数MoMHCG值以样本均数和标准差作为参数时,指标AFP的正态性较好,HCG仍不服从正态;Z=0.31时MoM指标SL转换后正态性明显改善. 结论: Johnson分布体系中SL分布族在我国唐氏综合征产前筛查指标HCG的MoM值的正态性转换中具有一定的应用价值.