Down综合征研究的某些进展（讲座）

Down综合征(Down Syndrome,DS)又称21-三体综合征、先天愚型。DS是研究最早、最常见的染色体病之一,本文拟就DS近年来某些研究情况讨论如下。 病因 DS有三种主要细胞遗传学类型,标准型(21-三体型)、易位型和嵌合型。DS特异性表型出现与     

Down综合征患儿睡眠特征多导睡眠图的回顾性研究

目的 探讨Down综合征患儿的睡眠结构和基本睡眠参数的特点。方法 选取10例Down综合征患儿为Down组，采用染色体核型检查进行Down综合征的诊断，其中男7例，女3例，年龄中位数8岁2个月；选取声带小结患儿14例及突发性耳聋6例患儿为对照组，其中男12例，女8例，年龄中位数8岁9个月。两组患儿均接受整夜多导睡眠图监测，按中华医学会耳鼻咽喉科学分会制定的儿童阻塞性睡眠呼吸暂停低通气综合征（OSAHS）诊疗指南（草案）中的标准进行呼吸事件的定义和OSAHS的诊断，阻塞性呼吸暂停指数（OAI）每小时≤1次或呼吸暂停低通气指数(AHI) 每小时≤5次，最低血氧饱和度(LSaO2)≥0.92可以排除OSAHS。应用Mann-Whitney U和精确概率检验，比较Down组和对照组的睡眠结构，并进行睡眠期LSaO2、OAI、AHI、脑电醒觉反应指数及睡眠期肢体运动事件指数的比较。结果 ①两组间在年龄、性别和体重指数等差异无统计学意义（P＞0.05）；②Down组和对照组比较，快动眼睡眠比例减少，且差异有显著统计学意义（Z=-2.6，P= 0.009）；③睡眠期LSaO2较对照组显著下降（P＜0.05），OAI、AHI及睡眠期肢体运动事件指数Down组较对照组显著升高（P＜0.05）；④10例Down综合征患儿中有6例符合OSAHS诊断，6例中有5例为男性。结论 Down综合征患儿存在睡眠呼吸紊乱，应使用多导睡眠检测的方法尽早发现睡眠呼吸紊乱的问题。     

Down综合征合并先天性食管蹼型狭窄一例

患儿：男．1岁半。因反复进食后呕吐1年余入院。患儿生后不久即被家长发现哺乳后出现呕吐，随患儿长大，经常出现进食后呕吐．且只能进食稀薄流质饮食。     

特殊教育对Down's综合征儿童的影响

目的探讨特殊教育对Down’s综合征（Down’ssyndrome,DS）儿童的认知和社会适应能力的影响。方法在2004年9月～2006年12月用家庭环境问卷,图片词汇测试和婴儿-初中学生社会生活能力量表对在特殊学校就读的25名DS儿童以及22名散居DS儿童进行测试。两组儿童基本情况匹配。结果散居DS儿童的图片词汇测试初分显著低于入学DS儿童组（P〈0.05）。入学DS儿童的运动和交往能力明显优于散居DS儿童组（P〈0.05）。与生活能力各维度明显相关。分别控制年龄因素和图片词汇测试初分进行偏相关分析,各维度与图片词汇测试初分及年龄的相关性具统计学意义（P〈0.05）。结论入学DS儿童的词汇理解能力和社会适应能力明显优于散居DS儿童;词汇理解能力及年龄与社会适应能力有明显相关性。     

儿科造血系统疾病新进展

本文简述缺铁性贫（IDA）、再生障碍性贫血（再障）、珠蛋白生成障碍贫血（地贫）和白血病等儿科常见造血系统的研究进展。一些新的血液分析检测参数对IDA的重要途径。造血干细胞移植重建正常造血和免疫功能对治疗业重再障碍有效,免疫抑制剂治疗适合于无合适供体作造血干细胞移植的严重再障者。预防重型地贫是最受关注的研究之一,其预防策略是进行筛查、指导合理婚配,对于重型地贫高危胎儿进行产前基因诊断,阻止重型地贫患儿的出生。造血干细胞移植是重型地贫的最有效手段。小儿白血病的疗效在近年有了明显的提高,国内一些条件较好的地区小儿急淋白血病的疗效在首次诱导治疗的完全缓解率可达98%以上,持续完全缓解率达80%。     

维甲酸相关综合征1例

患儿 ,男 ,9岁 ,因双下肢疼痛、面黄乏力 1个半月 ,发热 5～ 6ｄ入院。 1个半月前无明显诱因出现双下肢疼痛 ,无红肿及活动受限 ,伴面黄乏力、食欲减退 ,近 5～ 6ｄ发热 ,体温达4 0℃。查体 :精神不振 ,面色苍黄 ,浅表淋巴结不大 ,心肺无殊 ,腹软 ,肝脾不大 ,双下肢触痛 ,关节无红肿 ,活动可。血ＷＢＣ 7.5× 10 9/Ｌ ,ＲＢＣ 2 .76× 10 12 /Ｌ ,Ｈｂ 74 ｇ/Ｌ ,ＰＬＴ 188×10 9/Ｌ ,幼稚细胞占 0 .34。骨穿确诊为急性早幼粒细胞白血病 (ＡＰＬ) ,给全反式维甲酸 (ＡＴＲＡ) 10ｍｇ ,3次 /ｄ ,用药后3ｄ出现口唇干裂出血、发热、咳嗽、球…     

儿童血液系统疾病临床研究进展

2008年中国充满了机遇,也充满了挑战.儿童血液专业顺应时代的要求,在血液肿瘤、贫血及出血性疾病等方面取得了一定的临床研究进展.现将2008年我国儿童血液系统疾病的工作概述如下.     

21—三体综合征临床与机制研究进展

21-三体综合征(Down syndrome,Ds)即先天愚型,是一种最常见的常染色体畸变。1866年Langdon Down首次进行描述,1959年Le jeune等证实为21号染色体三体性所致。该综合征是小儿先天性智力低下中最常见的原因,也是最常见的遗传病之一。本病的群体发生率约为1/700～1/800,患病率随母亲年龄增长而上升。近年来,随着分子生物学的发展,对本综合征的研究有了进一步的新见解。本文综述近年来21-三体综合征研究的有关进展。     

异基因造血干细胞移植治疗高IgM综合征研究进展

高IgM综合征(hyper IgM syndrome,HIGM)是一组由单基因突变导致的罕见的原发性免疫缺陷病(primary immunodeficiency diseases,PID)。异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,all...     

Down syndrome and breastfeeding

AIM: The aim of the study was to investigate the frequency of breastfeeding among children with Down syndrome. METHODS: The mothers of 560 children with Down syndrome attending four university hospitals in Italy were interviewed and the neonatal clinical records retrieved. Information was collected on the type of infant feeding and on why some mothers had not breastfed their children. Two groups of healthy children whose feeding habits had been previously investigated were recruited as control subjects (1601 and 714, respectively). A paediatrician in each hospital was interviewed about the neonatal admission policy of children with Down syndrome. RESULTS: Among the 560 Down children, 246 (44%) were admitted to the neonatal unit. Compared with the two control groups, children with Down syndrome were significantly more frequently bottle-fed (57% vs 15% and 24%, respectively, odds ratio 7.5, 95% CI 6.0-9.4 and 4.2, 95% CI 3.3-5.4. respectively). Only 30% of infants admitted to the neonatal unit were breastfed. The main reasons reported by the mothers for not having breastfed were infants' illness in infants who had been admitted to the neonatal unit and frustration or depression, perceived milk insufficiency and difficulty with suckling for those babies who had not been admitted to the unit. The paediatricians reported that the admission of a baby with Down syndrome to the neonatal unit could sometimes take place not for medical reasons, but for diagnostic work-up or for a more appropriate diagnosis and to maintain communication with the family. CONCLUSIONS: Down syndrome babies are less frequently breastfed compared with healthy children. Support in breastfeeding should become a relevant point of health supervision for children with Down syndrome.     

Translocation Down’s syndrome

Among the 500 Down syndrome children karyotyped , 15 (3%) were due to translocation; 10 were 21;21 translocation and five 14;21. There were 9 cases of de novo translocations, while 6 were inherited from father or mother. Family history was characteristic in all the translocation cases, with younger parental age, fetal wastage in the family, recurrence and with the affected child often being either the first or the only liveborn in the family. The pattern of translocation in Madras and the significance of family history in genetic counselling are discused.     

Clinical implications of immune-mediated diseases in children with Down syndrome

Children with Down syndrome have changes in their innate and adaptive immunity, which contribute to increased rates of infections, autoimmune diseases, and haematological malignancies. While improved care for congenital heart disease has decreased mortality and morbidity, complications related to immune-mediated diseases continue to limit the life expectancy in Down syndrome. Infectious diseases are common and have a significant effect on development, behaviour and quality of life. Infection frequency and severity are influenced by various anatomical and physiological alterations in addition to immunological changes in Down syndrome. Thus, prevention of respiratory tract infections requires a multifactorial approach. This could include additional active and/or passive immunizations, prophylactic antibiotics, immunoglobulin replacement and ear, nose and throat surgical interventions. Autoimmune conditions like coeliac disease, type I diabetes mellitus and thyroid disease are classically mentioned in the context of Down syndrome. However, autoinflammatory conditions are more prevalent as well. Screening for autoimmune diseases is required and immunosuppression has to be used with caution. Future studies should address optimal screening programmes for immune-mediated diseases in individuals with Down syndrome, as well as the effect of immune modulation, to further decrease morbidity and mortality, and improve the quality of life of individuals with Down syndrome.     

Stenosis of pulmonary veins in Down syndrome

Two patients with Down syndrome, intracardiac communications and elevated pulmonary arteriolar resistance presented early in life. Both patients had significant stenosis of pulmonary veins. The progressive nature of the stenosis is illustrated in one patient. Pulmonary venous stenosis in Down syndrome has been recorded only twice before in the literature, and may play a part in the early onset of pulmonary vascular occlusive disease in some patients.     

An anthropometric study of body size in Down syndrome

Thirty anthropometric measurements were recorded in 59 cases of Down syndrome. The most affected segments of the body were length and circumference of the head. The head form in Down syndrome varied from brachycephaly to hyperbrachycephaly, and a flat occiput. Down syndrome cases were notably shorter in stature, however, trunk height was only slightly reduced. Legs were more severely affected. Shortness of stature was due to failure of the legs to grow in normal fashion. Dimensions of face lagged in both height and width. The Down syndrome cases retained their round facies. Ears were small in size. This represents persistence of infantile body proportions. Weight was only slightly reduced.     

Transient leukemia in newborns with Down syndrome

Children with Down syndrome (DS) have a 10- to 20-fold increased risk of developing leukemia, particularly acute megakaryocytic leukemia. Newborns with DS or trisomy 21 mosaicism may exhibit a particularly unique form of leukemia that historically has been associated with a high rate of spontaneous remission. This transient leukemia (TL) has been shown to be a clonal proliferation of blast cells exhibiting megakaryocytic features. Its true incidence remains to be determined. At presentation, many infants are clinically well with only an incidental finding of abnormal blood counts and circulating blasts in the peripheral blood. However, in approximately 20% of cases, the disease is severe and life-threatening, manifesting as hydrops faetalis, multiple effusions, and liver or multi-organ system failure resulting in death. Of those children who enter a spontaneous remission, 13-33% have been found to develop subsequent acute megakaryoblastic leukemia, usually within the first 3 years of life, which if left untreated is fatal. This unique TL of the DS newborn has been the subject of recent clinical cooperative group trials as well as many biological and genetic research efforts. We summarize here the known clinical, biological, and cytogenetic features of TL associated with DS.     

Cholelithiasis in infants with Down syndrome: report of two cases

Down syndrome is a chromosomal disorder most often observed in the newborn period. Various facial, limb and internal abnormalities are found in this disorder but cholelithiasis in infancy has been described in only one report. We report two infants with Down syndrome associated with cholelithiasis. Except for polycythemia and indirect hyperbilirubinemia, no hemolytic process or biochemical abnormalities were evident in both patients. We believe that the cause of gallstones in our cases may have been polycythemia in the newborn period. To our knowledge this is only the second report of gallstones in infancy in Down syndrome.     

Down syndrome and the enteric nervous system

Down syndrome (DS) is the most common chromosomal abnormality occurring in humans. Up to 77% of DS children have associated gastrointestinal (GI) abnormalities, which may be structural or functional in nature. Functional disturbances may, in turn, affect the outcome of corrective surgical procedures, prompting to caution. It is becoming clear that the processes affecting the enteric nervous system (ENS) in DS not only affect the micro-anatomy but also nerve function, and there is some histological evidence of ENS variations in both human and DS animal models. This suggests that developmental disorders of the ENS are probably fundamental to the functional GI disturbances encountered in patients with DS. The anomalous brain development, function and resulting intellectual impairment associated with DS appears to result from the genetic imbalance created by the trisomy of chromosome 21. The possible links between the brain, GI and ENS involvement are not as yet entirely clear. Neurotropic factors affecting brain development during embryogenesis are probably interlinked with ENS development, but the precise mechanism of how this occurs has yet to be established. This study explores what is known about the ENS dysfunction in DS and reviews the possible importance of chromosome 21 located and other genes in its etiology. Functional motor disturbances of the esophagus and colon are not uncommon and may be congenital or acquired in nature. The most prominent of these include esophageal dysmotility syndromes (e.g. achalasia, gastroesophageal reflux, dysphagia) as well as a higher incidence of chronic constipation and Hirschsprung's disease (HSCR) (2-15%) occurring in association with DS. Chromosome 21 itself is thought to be the site of a modifier gene for HSCR. Recently identified candidate genetic mechanisms provide unique insights into the genetic background of the neurological and cognitive disorders associated with DS. Although the role of the triplicated chromosome 21 and genetic dosage remain important, the additional role of other chromosome 21 genes in the etiology of ENS developmental anomalies remains undetermined and requires ongoing research.