Height and weight of Tokyo schoolchildren with and without intellectual handicaps.

The heights, weights and Rohrer Indices (W/H3; RIs) of Tokyo schoolchildren born in 1972/73 with and without intellectual handicaps were compared from 6 to 15 years. The samples of children consisted of 303 children with no intellectual handicaps ('controls') and 308 children with intellectual handicaps including subgroups with Down's syndrome (39 children), autism (49 children) and epilepsy (58 children). Boys and girls with no intellectual handicaps were at all ages significantly taller than schoolchildren with intellectual handicaps. However, there were few significant differences in mean weight between children with and without intellectual handicaps--only in boys at age 15 years and girls at 6, 7, 11 and 12 years. The mean RIs of boys and girls with intellectual handicaps were at all ages significantly higher than those of controls. The subgroup of children with Down's syndrome were the shortest and had the highest mean RI at all ages. Children with epilepsy were also significantly shorter than children with no intellectual handicaps but did not differ much in RI. Autistic children did not differ in height from controls, except for autistic boys who at the ages 6-12 years were significantly taller, indicating a comparatively earlier maturational rate of this specific sample. Autistic boys had a higher RI than controls at 9, 11, 12, 13 and 14 years but autistic girls did not differ significantly from controls at these ages.     

Down's syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis

The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population. The age of onset for leukemia in these children is bimodal, peaking first in the newborn period and again at 3-6 years. This increased risk extends into adulthood. All cytogenetic types of Down's syndrome apparently predispose to leukemia. The proportion of acute lymphoblastic leukemia and acute nonlymphoblastic leukemia in patients with Down's syndrome is similar to non-Down's syndrome leukemia patients matched for age. There are case reports in which leukemia, Down's syndrome, and other chromosomal aberrations cluster within a family. In these kindreds, there may be a familial tendency toward nondisjunction. Congenital leukemia also occurs with increased frequency in Down's syndrome patients, and is characterized by a preponderance of acute nonlymphoblastic leukemia (similar to non-Down's syndrome patients). Transient leukemoid reactions have been observed in Down's syndrome patients, as well as in phenotypically normal children with constitutional trisomy 21 mosaicism. The transient leukemoid reactions are characterized by a high spontaneous remission rate. However, in some Downs syndrome patients with apparent transient leukemoid reaction, leukemia relapse following periods of spontaneous remission have been reported. Cytogenetic studies of leukemic cells in Down's syndrome patients show a tendency toward hyperdiploidy. Besides trisomy 21, there is no other specific cytogenetic abnormality that is characteristic of the leukemia cells in Down's syndrome patients. The possible mechanisms for leukemogenesis in Down's syndrome patients may involve factors at the levels of the organism, the organ/system, the cell, the chromosomes or the DNA.     

江苏地区以人群为基础的唐氏综合征产前筛查和诊断研究

目的 对江苏省中期妊娠孕妇的胎儿进行唐氏综合征筛查和诊断,减少21三体综合征患儿出生.方法 用分层和整群抽样相结合的多阶段抽样方法,对江苏省怀孕15～20周的26 803名妇女采用时间荧光分辨法进行母血清常规二联筛查,筛查出的高风险孕妇进行羊膜腔穿刺、细胞培养、染色体分析.出生儿童通过面访和外周血染色体培养确诊.结果 血清筛查和羊水染色体检查,确诊6例胎儿;出生儿童随访和外周血染色体分析确诊3例,共确诊9例唐氏综合征,产前筛查检出率为67%(6/9).结论 产前筛查和诊断可以减少唐氏综合征患儿出生,提高出生人口素质.但是应提高产前筛查的准确性,最大限度地降低假阴性,减少或杜绝漏诊发生.     

Peripheral blood cell counts in infants with Down's syndrome

The current literature indicates that several abnormalities have been observed in the three hematopoietic cell lines of infants with Down's syndrome. This prospective, longitudinal study was designed to clarify the physiological variation in peripheral blood cell values of children with Down's syndrome by following 25 such infants during their first year of life. Apart from polycythemia in the first week of life, the hemoglobin concentration was, in general, the same as in normal term infants. At 9–12 months of age values for mean corpuscular hemoglobin and mean corpuscular volume tended to be elevated. Serum erythropoietin concentrations were low to normal. White blood cell counts were slightly lower in children with Down's syndrome than in normal children. The study infants had profound thrombocytosis from the age of 6 weeks to the end of follow-up at 1 year. This study, the first longitudinal follow-up of such subjects, indicates that infants with Down's syndrome often have evidence of polycythemia soon after birth and red blood cell macrocytosis and thrombocytosis later in infancy. In conclusion, we carried out peripheral blood cell counts in 25 infants with Down's syndrome, but with no actual hematological disturbance, during their first year of life, and compared them with values for normal term infants.     

A survey of Down's syndrome under general practitioner care in Scotland

A survey of all general practitioners in Scotland has revealed details of 1,251 individuals with Down's syndrome being cared for by their family doctor; 1,150 were living at home.

Eighty-two per cent of doctors responded to the questionnaire. High prevalence rates have been noted in the Western Isles and in Shetland. The survey confirms reports of a lowering of maternal and paternal age in Down's syndrome; 72 per cent of the mothers and 56 per cent of the fathers of Down's syndrome children born since 1971 were under 35 years at the time of birth. The survey also revealed an increase in the number of Down's people living with either one parent or relatives with increasing age. It is hoped that further research will be carried out into the problems facing Down's individuals and their families through the medium of general practice.

     

A double logistic comparison of growth patterns of normal children and children with Down's syndrome.

A double logistic model was used to compare six parameters of growth in standing height of 31 children with Down's syndrome with 136 children from the California Guidance Study. Multivariate analysis of variance of the growth data showed that while there were significant differences in all six parameters favouring the normal over the Down's children, there were no significant differences with respect to error of fit. Multivariate analysis with final height as a covariate revealed that differences between the normal and the Down's children in the prepubertal and adolescent components were explainable by differences in final height. In summary, the double logistic model, when applied to this sample of Down's children, identified those well defined logistic components which are characteristic of the growth of normal children, the differences being those of degree, not of form.     

A fetal testis with intratubular germ cell neoplasia (ITGCN).

A fetal testis with abnormal germ cells similar to the cells of intratubular germ cell neoplasia (ITGCN) or so-called carcinoma in situ is presented. Elective abortion was performed in week 18 of the pregnancy of a 26-yr-old woman, because of 21 trisomy (Down's syndrome) at amniocentesis. At microscopical examination abnormal germ cells were found, similar to those occurring in the adult testis and with the same distribution as those described in ITGCN in children with dysgenetic gonads and with androgen insensitivity syndrome. PAS positivity and placental-like alkaline phosphatase (PLAP) was demonstrated in the abnormal germ cells. The finding indicates that the first event of germ cell tumor oncogenesis may take place before birth, in utero or even before. The occurrence of ITGCN in Down's syndrome has not been reported previously but is likely to occur, as there is evidence that these patients have increased risk of developing germ cell tumors.     

Paternal age effect in Down''s syndrome

Increasing incidence of Down's syndrome with advancing paternal age for given maternal age has been demonstrated. Comparisons are made between an almost complete Down's syndrome sample from the Copenhagen Metropolitan Area and a randomly selected sample of births from the same area and the same time period. Men above 55 years have a significantly increased risk of getting children with Down's syndrome.     

Adults with Down''s syndrome: the prevalence of complications and health care in the community

BACKGROUND: Individuals with Down's syndrome are predisposed to a variety of medical conditions which can impose an additional, but preventable, burden of secondary disability. Although there are guidelines for health checks and medical management of children with Down's syndrome, the needs of adults are relatively neglected. AIM: To determine the prevalence of common medical problems in adults with Down's syndrome, and to assess current practice regarding medical surveillance of these patients. DESIGN OF STUDY: Detailed notes analysis. SETTING: Data were obtained from the primary care records of adults with Down's syndrome living in the Newcastle upon Tyne and Gateshead areas. METHOD: Case notes were reviewed to obtain details regarding complications and to determine the frequency of medical surveillance of individuals with Down's syndrome. RESULTS: Complications such as hypothyroidism, celiac disease, and obesity occur more frequently in adults with Down's syndrome than previous paediatric prevalence studies suggest. Surveillance of common complications that occur in individuals with Down's syndrome is infrequent. In this study, 48% of adults with Down's syndrome had not seen a doctor in the previous 12 months and 33% had not had a medical assessment in the previous 3 years. CONCLUSION: Many individuals with Down's syndrome do not have access to regular healthcare checks, despite the high frequency of common medical complications in adult life. Debate regarding the practicality and relevance of introducing regular health checks is warranted.     

Assessment of multiplex fluorescent PCR for screening single cells for trisomy 21 and single gene defects

A great majority of patients seeking preimplantation genetic diagnosis (PGD) are women >35 years of age. In addition to being carriers for single gene defects, these women also have a higher risk of having children with Down's syndrome (trisomy 21). For these patients, it would be advantageous if a diagnostic test for trisomy 21 was developed, which could be used in conjunction with tests for single gene defects. Here, we assessed the feasibility of developing an accurate genetic test for diagnosing trisomy 21 and the mutation causing spinal muscular atrophy (SMA) in single cells using multiplex fluorescence polymerase chain reaction (PCR). Single- and two-round PCR were developed using a combination of primers for the survival motor neuron (SMN) gene exons 7 and 8 and two chromosome 21 short tandem repeats (STRs), D21S226 and D21S11. After only 36 cycles, 88 and 68% of normal single cells were screened for SMA mutations and trisomy 21 respectively. In multiplex PCR using only two primers (SMN exon 7 and D21S11) instead of four, the efficiency of SMA diagnosis was increased to 93%. In the same reactions, the D21S11 alleles were detected in 83% of the normal single cells. Clinical applications of this assay should enable detection of those embryos that have inherited three heterozygous alleles and, therefore, benefit many PGD patients who are at an increased risk of Down's syndrome.     

应用实时荧光定量PCR快速分子诊断唐氏综合征

目的探讨一种快速、准确诊断唐氏综合征的方法。方法采用实时荧光定量PCR技术，对25例唐氏患者、50名正常人外周血标本，扩增21号及1号、19号染色体上的多态位点，定量分析比较正常组及唐氏患者组的4对△Ct值。结果唐氏患者组△Ct值明显低于正常组，两组比较差异有统计学意义（P〈0．001）。初步建立了临床应用的参考值范围，可以有效区分出唐氏样本和正常样本。结论应用实时荧光定量PCR技术可快速、准确诊断唐氏综合征，为唐氏综合征的快速产前诊断开辟了新的途径。     

An anomaly in the inheritance of haptoglobin types in Down''s syndrome: A study of mother-child pairs

A sample of 95 mother-child pairs provided evidence that plasma haptoglobin (Hp) types are inherited in an unusual manner by children with Down's syndrome. Homozygous mothers gave birth to more homozygotes and fewer heterozygotes than expected. Among offspring of heterozygous mothers, the frequencies were distributed essentially as expected. No abnormality was found in a normal control sample of 151 mother-child pairs. Using this material it was demonstrated that the anomalous Hp inheritance in Down's syndrome was not due simply to an increase in maternal age when the children were born.     

Prenatal screening for Down's syndrome with use of maternal serum markers.

BACKGROUND. Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Down's syndrome. METHODS. We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Down's syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS. Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Down's syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Down's syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS. Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.     

多普勒超声观察创伤性寰枢椎不稳手术前后椎动脉血流的变化

目的探讨创伤性寰枢椎不稳患者内固定手术前后椎动脉血流的变化。方法32例创伤性寰枢椎不稳患者,其中男性22例,女性10例;年龄22～57岁,平均年龄38岁。手术前及内固定术后,均应用彩色多普勒超声测量颈椎1、2间和颈椎5、6间椎动脉血流速度、阻力指数。并对检查结果进行对比分析。结果32例创伤性寰枢椎不稳患者术前椎动脉血流39侧异常,25侧正常。内固定术后39侧异常者中35侧恢复正常,4侧无变化,3侧术前正常变为术后异常。结论创伤性寰枢椎不稳可导致椎动脉血流变化,手术复位内固定后增加了寰枢椎稳定性,可改善椎动脉血液供应。     

Screening for fetal Down's syndrome in pregnancy by measuring maternal serum alpha-fetoprotein levels

Although the risk of Down's syndrome increases with maternal age, women under 35 bear about 80 percent of the infants born with this condition. We prospectively investigated the utility of measuring maternal serum alpha-fetoprotein during the second trimester in women under 35 in order to identify pregnancies in which the fetus was affected with Down's syndrome. Over a two-year period, 34,354 women in this age group were screened. Amniocentesis was offered when the risk of Down's syndrome, calculated as a function of maternal age and maternal serum alpha-fetoprotein concentration adjusted for maternal weight and race, was 1:270 or higher, the risk for a 35-year-old woman. This threshold was exceeded in 1451 women in whom gestational age was confirmed by ultrasound; 9 women in this group had a fetus with the syndrome. In three women whose fetuses had trisomy 18 and one whose fetus had trisomy 13, the calculated risk of Down's syndrome was 1:270 or higher. Thus, among women in whom the risk exceeded our cutoff point, 1 in 161 were found to have a pregnancy in which the fetus was affected with Down's syndrome; the figure was 1 in 112 for all autosomal trisomies. Eighteen pregnancies involving Down's syndrome, three involving trisomy 18, and two involving trisomy 13 were not associated with a calculated risk above the cutoff point. The available data indicate that in our population, using a cutoff for risk at which 5 percent of women under 35 are offered amniocentesis, we will detect one quarter to one third of pregnancies in which the fetus has Down's syndrome.     

Serum dopamine-β-hydroxylase levels in Down's syndrome

Serum dopamine-β-hydroxylase (DBH) and serum immunoreactive (IR) DBH levels were measured in patients with Down's syndrome. Serum DBH activity was markedly reduced in Down's syndrome patients as compared with age matched, normal controls or non-mongoloid, disturbed children. Serum IR-DBH levels were also markedly reduced in Down's syndrome. The possible factors responsible for the observed reduction in serum DBH levels (active and inactive enzyme levels) in Down's syndrome were investigated.     

寰枢椎椎弓根螺钉治疗寰枢椎不稳的临床疗效和手术策略

目的探讨运用寰枢椎椎弓根螺钉治疗创伤性寰枢椎不稳的临床效果和手术策略。方法 2007年～2010年中运用寰枢椎椎弓根螺钉治疗创伤性寰枢椎不稳15例,观察术后近期疗效、植骨融合及并发症。结果 14例患者均顺利完成手术,1例患者由于置钉困难改行寰枢椎后方植骨融合术。寰椎置钉28枚,未发现神经损伤。枢椎置钉28枚,未出现椎动脉损伤。术后渗血1例,颈部肿胀3例,无神经症状加重,无切口感染和脑脊液漏,随访3个月～3年,平均1.8年,所有病例均成功寰枢椎融合,颈椎序列和生理曲度良好,无明显丢失,未见内固定松动或断裂。随访时,脊髓功能Frankel分级评分3例D级均恢复到E级。结论寰枢椎椎弓根螺钉内固定技术治疗创伤性寰枢失稳的可操作性、力学稳定性及融合率均取得满意效果,虽然操作上技术要求较高,并有损伤C2神经根、寰枢椎间静脉丛及椎动脉的可能性,但仍不失为一种疗效可靠的方法,可以在有条件的基层医院开展。     

Observations on the levels of γG, γA, and γM globulins, anti-A and anti-B agglutinins, and antibodies to Escherichia coli in Down''s anomaly

The levels of gammaG, gammaA, and gammaM globulins were estimated in a group of patients with Down's anomaly and in groups of mentally retarded children and normal children, matched for age and sex, using an immunological method.Higher levels of gammaG globulin were observed in patients with Down's syndrome, in association with a small but significant lower concentration of gammaM globulin.The titres of anti-A and anti-B agglutinins and antibodies to Escherichia coli, estimated before and after treatment of serum with 2-mercaptoethanol, were found to be within normal levels.These data seem to suggest that patients with Down's syndrome do not produce ;faulty' immunoglobulins as has been previously postulated. It is suggested that the abnormal levels of immunoglobulins found in Down's anomaly are not peculiar to patients with Down's syndrome but occur in other disorders in which the reticuloendothelial system or the lymphocytes are involved.     

Thyroid dysfunction in institutionalised Down's syndrome adults

This study of 111 institutionalised Down's syndrome subjects and 74 controls found a relatively low risk of hypothyroidism in both groups compared with certain other studies of Down's subjects, which found very high rates of thyroid hypofunction. However, the Down's syndrome group had a significantly raised risk of hypothyroidism (9%), hyperthyroidism (1.8%) and the presence of thyroid microsomal antibodies (29%) compared with the controls and with laboratory reference data. It is recommended that thyroid function testing should be routine in older Down's syndrome subjects, with special attention being given to the clinical status of those with microsomal antibodies present.     

杂合型单核苷酸多态性定量焦测序测定法用于唐氏综合征快速诊断的探索

目的 通过筛查人21号染色体上的杂合型单核苷酸多态性(single nucleotide polymorphism,SNP)位点,初步建立基于定量焦磷酸测序反应的唐氏综合征分子诊断方法.方法 基于改进引物设计的等位基因特异性扩增法,在21号染色体上选取7个SNP位点进行杂合子筛选,通过焦测序法检测SNP中两个等位基因型的比值,并作为诊断唐氏综合征的依据.结果 通过对84名正常中国人基因组样本进行筛查,得到6个杂合率较高的SNP位点.6个SNP位点的杂合子覆盖率为92.9%.应用这6个SNP位点对10例唐氏综合征患者的样本进行了焦测序定量检测,结果表明10例患者样本中有9例样本的两个基因型比值为2:1或1:2,1例未检出杂合子,检出率为90%.结论 初步建立了一种唐氏综合征辅助诊断方法,具有成本低、操作简单、快速和结果明了的优点,可以有效地快速诊断唐氏综合征,为今后进一步完善该方法,并将其用于临床诊断奠定了基础.