21三体综合症

21三体综合症 09生科02 肖梅琴，倪时云，张美清，张诗琪，李洁，陈少芳，黄婷婷 21三体综合征 21三体综合征患儿 21三体综合征又称先天愚型或Down综合症属常染色体畸变，是小儿染色体病中最常见的一种，活婴中发生率约1/(600,800)，母亲年龄愈大，本病的发病率愈高。60%患儿在胎儿早期即夭折流产。21三体综合征包含一系列的遗传病，其中最具代表性的第21对染色体的三体现象，会导致包括学习障碍、智能障碍和残疾等高度畸形。 21三体综合征即Down综合征(DSDown Syndrome)，又称先天愚型(OMIM#190685)为染色体结构畸变所致的疾病，患者核型为47,XX(XY),+21 产生原因是卵子在减数分裂时21号染色体不分离，形成异常卵子。 21三体的形成与母亲的年龄增高(35岁以上)和年龄过小(20岁以下)有关，目前报道与父亲年长也有关。 唐纳氏综合症 DS的一般特点 1(综合征 2(多数情况下为新发生的、散在的病例 3(同卵双生具有一致性 4(男性患者没有生育力，而极少数女性患者可生育 5(随母亲年龄增加该病的发病率也升高，尤其是大于35岁时 6(病人的预期寿命短，且患者到中年时大脑呈现淀粉样斑，与Alzheimer病(即老年痴呆症)相符，伴痴呆症状;免疫功能缺陷，先天性心脏病也增加，用抗生素和心脏外科手术治疗可延长病人的寿命 ncluding based life support (BLS), and senior heart life support (ACLS), and based trauma life support (BTLS) and senior trauma life support (ATLS) of based knowledge; common emergency technology of application; common emergency of causes identification, and clinical performance and the processing specification; common emergency auxiliary check of select refers to levy, and results judge and the clinical meaning; Indications, effects of common emergency drugs, side effects, as well as specific applications (medicine, for expansion of vasoactive drugs, cardiac diuretic, antispasmodic and anti-asthmatic drugs, analgesic drugs, Hemostatic, antiarrhythmic drugs, such as Cortina). Understand: the new development of the theory of life support; cardiac respiratory and cardiopulmonary resuscitation after cardiac syndrome etiology, pathophysiology, clinical manifestations, diagnosis, and treatment. 2. basic requirements (1) species and cases of study requirements: disease disease fever acute abdominal pain chest pain and difficulty breathing faint coma shock in acute poisoning with cardiac respiratory arrest bleeding (hemoptysis, hematemesis, hematuria, etc) requires at least 45 cases of arrhythmia. (2) basic skills requirements name name heart lung 患者身体特征 以下特征并非全部出现在患者身上，根据个人差异，也有身体特征上不明显的例子。 身材矮小，肌肉紧张度低下，体力低下，颈椎脆弱。头部长度较常人短，面部起伏较小，鼻子，眼睛之间的部分较低，眼角上挑，深双眼皮。耳朵上方朝内侧弯曲，耳朵整体看上去呈圆形而且位置较低。舌头比较大。脖子粗壮。手比较宽，手指较短，拇指和食指之间间隔较远，小指缺少一个关节，向内弯曲。手掌的横向纹路只有一条，指纹为弓状。脚趾第一趾与第二趾之间间隔也比较大。 临床表现 21,三体综合征患儿的主要特征为智能低下、体格发育迟缓和特殊面容。患儿眼距宽，鼻梁低平，眼裂小，眼外侧上斜，有内眦赘皮，外耳小，硬腭窄小，舌常伸出口外，流涎多;身材矮小，头围小于正常，骨龄常落后于年龄，出牙延迟且常错位;头发细软而较少;四肢短，由于韧带松弛，关节可过度弯曲，手指粗短，小指向内弯曲。 皮肤纹理特征有:通贯手，atd角增大;第4，5指桡箕增多;脚拇指球胫侧弓形纹和第5指只有一条指褶纹等。 患儿在出生时即已有明显的特殊面容，且常呈现嗜睡和喂养困难。随着年龄增长，其智能低下表现逐渐明显，动作发育和性发育延迟。约30%患儿伴有先天性心脏病等其他畸形。因免疫功能低下，易患各种感染，白血病的发生率也增高10,30倍。如存活至成人期，则常在30岁以后出现老年性痴呆症状。 细胞遗传学 类型划分 按照核型分析可将21,三体综合征患儿分为三型，其中型和易位型在临床上不易区别，嵌合型的临床表现差异悬殊，视正常细胞株所占的百分比而定，可以从接近正常到典型表型。 标准型 患儿体细胞染色体为47条，有一条额外的21号染色体，核型为47。XX(或XY)，+21，此型占全部病例的95%。其发生机制系因亲代(多数为母方)的生殖细胞染色体在减数分裂时不分离所致。双亲外周血淋巴细胞核型都正常。 易位型 约占2.5%,5%。多为罗伯逊易位(Robertsonian translocation)， 唐纳氏综合症 ncluding based life support (BLS), and senior heart life support (ACLS), and based trauma life support (BTLS) and senior trauma life support (ATLS) of based knowledge; common emergency technology of application; common emergency of causes identification, and clinical performance and the processing specification; common emergency auxiliary check of select refers to levy, and results judge and the clinical meaning; Indications, effects of common emergency drugs, side effects, as well as specific applications (medicine, for expansion of vasoactive drugs, cardiac diuretic, antispasmodic and anti-asthmatic drugs, analgesic drugs, Hemostatic, antiarrhythmic drugs, such as Cortina). Understand: the new development of the theory of life support; cardiac respiratory and cardiopulmonary resuscitation after cardiac syndrome etiology, pathophysiology, clinical manifestations, diagnosis, and treatment. 2. basic requirements (1) species and cases of study requirements: disease disease fever acute abdominal pain chest pain and difficulty breathing faint coma shock in acute poisoning with cardiac respiratory arrest bleeding (hemoptysis, hematemesis, hematuria, etc) requires at least 45 cases of arrhythmia. (2) basic skills requirements name name heart lung 是只发生在近端着丝粒染色体的一种相互易位，亦称着丝粒融合，其额外的21号染色体长臂易位到另一近端着丝粒染色体上。其中，D/G易位最常见，D组中以14号染色体为主，即核型为46，XX(或 XY),14，+t(14q21q);少数为15号。这种易位型患儿约半数为遗传性，即亲代中有14/21平衡易位染色体携带者，核型为 45，XX(或XY)，,14，,21，+t(14q21q)。另一种为G/G易位，是由于G组中两个21号染色体发生着丝粒融合，形成等臂染色体t(21q21q)，或一个21号易位到一个22号染色体上，t(21q22q)，较少见。 嵌合体型 约占本症的2%,4% 患儿体内有两种以上细胞株(以两种为多见)，一株正常，另一株为21-三体细胞，本型是因受精卵在早期分裂过程中染色体不分离所引起，临床表现随正常细胞所占百分比而定。 种类 基本上分为三种类型: 第21对染色体的三体变异现象 染色体移位造成第14对染色体的变异标准型第21对染色体三体变异(Trisomy 21):又称廿一三体症，第21对染色体多出一条，细胞中有四十七条色体，占唐氏综合症患者的90-95% 这大多是由通常第1减数分裂期的不分离造成的。也有在减数第二次分裂时发生的情况。父母方通常都携带正常的染色体，婴儿是偶然形成的三体异常。 染色体移位型 占全体比例的5-6% ;细胞中多出一条染色体，附着在D组(第13、14、15对染色体)或者G组(第21对22对染色体)的染色体上，特别容易出现在第14对或第21对染色体上。移位型中一半左右是偶发性的，也就是父母双方都是正常染色体。另外一半是遗传性移位，父母有一方携带有这样的染色体，这在家族中常能找到相同病症的亲属。 无色体型 占全体比例的1-3% ;由第21对三体变异染色体结合体(占80%)和正常细胞结合体的体细胞分裂所产生的不分离造成。这种场合表现出来的临床现象较轻。通常父母方染色体正常，染色体的不分离在受精卵的细胞分裂过程中偶然发生，造成婴儿的部分细胞三体变异，部分细胞正常，极为罕见。 早期干预 21三体综合征患儿并非不可矫正，通过早期干预，可以和正常人一样学习生活和工作。 哪些人群发生“唐氏儿”的概率较大,专家提醒，下列7类夫妻属高发人群: ?妊娠前后，孕妇有病毒感染史，如流感、风疹等; ?受孕时，夫妻一方染色体异常 ?夫妻一方年龄较大; ?妊娠前后，孕妇服用致畸药物，如四环素等 ?夫妻一方长期在放射性荧幕下工作或污染环境下工作; ncluding based life support (BLS), and senior heart life support (ACLS), and based trauma life support (BTLS) and senior trauma life support (ATLS) of based knowledge; common emergency technology of application; common emergency of causes identification, and clinical performance and the processing specification; common emergency auxiliary check of select refers to levy, and results judge and the clinical meaning; Indications, effects of common emergency drugs, side effects, as well as specific applications (medicine, for expansion of vasoactive drugs, cardiac diuretic, antispasmodic and anti-asthmatic drugs, analgesic drugs, Hemostatic, antiarrhythmic drugs, such as Cortina). Understand: the new development of the theory of life support; cardiac respiratory and cardiopulmonary resuscitation after cardiac syndrome etiology, pathophysiology, clinical manifestations, diagnosis, and treatment. 2. basic requirements (1) species and cases of study requirements: disease disease fever acute abdominal pain chest pain and difficulty breathing faint coma shock in acute poisoning with cardiac respiratory arrest bleeding (hemoptysis, hematemesis, hematuria, etc) requires at least 45 cases of arrhythmia. (2) basic skills requirements name name heart lung ?有习惯性流产史、早产或死胎的孕妇 ?夫妻一方长期饲养宠物者。 21三体综合症的七大特征表现 (1)智力低下:为轻、中度，多数是中度精神发育迟滞，其智力随着年龄的增长而逐步降低，年龄从1岁增长至10岁，其平均智商(IQ)则从58下降至40以下。也有专家认为，在青少年期智商(IQ)相对稳定，以后才降低。大多数研究表明环境因素是影响智商(IQ)的重要因素，在良好环境中抚养的患者智商(IQ)相对较高。不同类型的患者智力低下的程度可不同，一般来说，三体型者最严重，易位者次之。易位型中以平衡易位者智力受累程度较小。由于患儿安静、温驯，为特殊教育训练提供较好条件，虽然在文化技能上很难达到小学1-2年级水平，但适应能力可有明显的改善，有一定的生活自理和劳动能力。 (2)语言发育障碍:患儿开始学说话的平均年龄为4-6岁，95%有发音缺陷、口齿含糊不清、口吃、声音低哑;1/3以上有语音节律不正常，甚至呈爆发音。 (3)行为障碍:大多性情温和，常傻笑，喜欢模仿和重复一些简单的动作，可进行简单的劳动，少数患者易激惹、任性、多动，甚至有破坏攻击行为，某些则显示畏缩倾向，伴有紧张症的姿势。 (4)运动发育迟缓:患儿在出生后的一段时期其运动功能与正常同龄儿差别可能不大，但随年龄增长其差别增大。在不同的患者中运动发育的情况也相差很大。先天愚型患者可执行简单的运动，如穿衣、吃饭等，但动作笨拙、不协调、步态不稳。 (5)生长发育障碍:先天愚型患者母体妊娠期较短，平均为262~272天。出生时身高较正常新生儿短l~3cm，头围基本正常，双顶径在正常范围，前后径相对较短，枕部平坦。大多数呈短头畸型。前后囟及前额缝宽，闭合迟，常出现第三囟(后囟上方的矢状缝增宽)。本病患儿出生后几天睡眠较深，吸吮、吞咽十分缓慢，甚至完全不能，故弄醒和喂养十分困难。80%的患儿肌张力普遍低下。 (6)特殊的外貌:双眼距宽，两眼外角上斜，内眦赘皮，耳位低，鼻梁低，舌体宽厚，口常半张或舌伸出口外，舌面沟裂深而多，手掌厚而指短粗，末指短小常向内弯曲或有两指节，40%患儿有通贯掌。跖纹中，拇趾球区胫侧弓状纹，拇趾与第二趾指间距大，关节韧带松弛或见肌张力低。 (7)约有1/2的病例并发先天性心脏病、易患传染性疾病和白血病。 怎样预防21三体综合症的发生 适龄生育为佳，高危患儿要做好产前诊断及咨询。一般认为产前诊断的指征有: ?高龄父母，母>35岁，父>55岁。 ?已生育过一个先天愚型，其再生育21-三体型的风险为1~1?3%。 ?父或母为平衡易位携带者，t(Dq21q)易位者，如为女性则子女患病率10~15%，男性3~5%;t(21q21q)易位者为100%，应劝绝育。 ?双亲中一方为嵌合体，生育患儿的危险性增高，一般认为嵌合型有遗传性，再发率高。 ?有先天愚型家族史并具有本病皮纹特征的孕妇。 ncluding based life support (BLS), and senior heart life support (ACLS), and based trauma life support (BTLS) and senior trauma life support (ATLS) of based knowledge; common emergency technology of application; common emergency of causes identification, and clinical performance and the processing specification; common emergency auxiliary check of select refers to levy, and results judge and the clinical meaning; Indications, effects of common emergency drugs, side effects, as well as specific applications (medicine, for expansion of vasoactive drugs, cardiac diuretic, antispasmodic and anti-asthmatic drugs, analgesic drugs, Hemostatic, antiarrhythmic drugs, such as Cortina). Understand: the new development of the theory of life support; cardiac respiratory and cardiopulmonary resuscitation after cardiac syndrome etiology, pathophysiology, clinical manifestations, diagnosis, and treatment. 2. basic requirements (1) species and cases of study requirements: disease disease fever acute abdominal pain chest pain and difficulty breathing faint coma shock in acute poisoning with cardiac respiratory arrest bleeding (hemoptysis, hematemesis, hematuria, etc) requires at least 45 cases of arrhythmia. (2) basic skills requirements name name heart lung ?习惯性流产者。此外对患者的家庭成员进行染色体检查，对末梢血细胞核型正常的父 母，应尽量做皮肤成纤维细胞或2种以上组织培养，尽可能检出平衡易位携带者和表型五 常的嵌合体。 ncluding based life support (BLS), and senior heart life support (ACLS), and based trauma life support (BTLS) and senior trauma life support (ATLS) of based knowledge; common emergency technology of application; common emergency of causes identification, and clinical performance and the processing specification; common emergency auxiliary check of select refers to levy, and results judge and the clinical meaning; Indications, effects of common emergency drugs, side effects, as well as specific applications (medicine, for expansion of vasoactive drugs, cardiac diuretic, antispasmodic and anti-asthmatic drugs, analgesic drugs, Hemostatic, antiarrhythmic drugs, such as Cortina). Understand: the new development of the theory of life support; cardiac respiratory and cardiopulmonary resuscitation after cardiac syndrome etiology, pathophysiology, clinical manifestations, diagnosis, and treatment. 2. basic requirements (1) species and cases of study requirements: disease disease fever acute abdominal pain chest pain and difficulty breathing faint coma shock in acute poisoning with cardiac respiratory arrest bleeding (hemoptysis, hematemesis, hematuria, etc) requires at least 45 cases of arrhythmia. (2) basic skills requirements name name heart lung