Prader-Willi综合征的临床筛查和基因诊断

目的 探讨临床疑似Prader-Willi综合征（PWS）患儿的临床筛查、基因诊断及确诊病例临床诊断评分结果的差异。方法 选取2016年7月至2018年12月收治的临床疑似PWS患儿94例为研究对象,应用甲基化特异性多重连接依赖性探针扩增（MS-MLPA）技术进行检测,对确诊患儿采用临床诊断评分进行评估,并分析确诊患儿的围生期特征。结果 MS-MLPA技术确诊PWS患儿11例,检出率为12%;其中男7例,女4例;中位确诊年龄3岁4个月（范围：25 d至6岁8个月）。11例PWS患儿中仅5例（45%）满足临床诊断标准。PWS患儿围生期主要特征有胎动减少9例（82%）、剖宫产11例（100%）、新生儿期肌张力低下11例（100%）、喂养困难11例（100%）及哭声低下11例（100%）。结论 对临床疑似的PWS患儿应及早进行基因检测确诊,单纯依靠临床诊断评分可能导致PWS漏诊。     

Prader-Willi综合征的临床筛查和基因诊断

目的 探讨临床疑似Prader-Willi综合征（PWS）患儿的临床筛查、基因诊断及确诊病例临床诊断评分结果的差异。方法 选取2016年7月至2018年12月收治的临床疑似PWS患儿94例为研究对象,应用甲基化特异性多重连接依赖性探针扩增（MS-MLPA）技术进行检测,对确诊患儿采用临床诊断评分进行评估,并分析确诊患儿的围生期特征。结果 MS-MLPA技术确诊PWS患儿11例,检出率为12%;其中男7例,女4例;中位确诊年龄3岁4个月（范围：25 d至6岁8个月）。11例PWS患儿中仅5例（45%）满足临床诊断标准。PWS患儿围生期主要特征有胎动减少9例（82%）、剖宫产11例（100%）、新生儿期肌张力低下11例（100%）、喂养困难11例（100%）及哭声低下11例（100%）。结论 对临床疑似的PWS患儿应及早进行基因检测确诊,单纯依靠临床诊断评分可能导致PWS漏诊。     

新生儿Prader-Willi综合征13例临床表型分析

目的 分析Prader-Willi综合征（PWS）新生儿期的临床表现,为临床早期筛选及进一步行分子诊断提供帮助。方法 回顾性分析2009年8月至2011年8月在北京军区总医院附属八一儿童医院依据MS-PCR和MS-MLPA方法确诊为PWS患儿的诊断、分型和临床表型资料,分析中国PWS新生儿期典型特征。结果 13例PWS进入分析,男9例,女4例,确诊年龄4～28 d。足月儿10例,早产儿2例,过期产儿1例。孕母高龄9例（69.2%）,羊水污染8例（61.5%）,羊水过多3例（23.1%）,胎膜早破5例（38.5%）,异常胎位4例（30.8%）,宫内窘迫9例（69.2%）。 9例为父源性15q11.2-q13区域缺失致病,4例为母源性同源二倍体。4例母源性同源二倍体患儿均可见中枢性肌张力低下和皮肤色素减退,吸吮缓慢2例(50.0%)、哭声微弱3例(75.0%)、男性隐睾1例(25.0%)、女性小阴唇3例(75.0%);均未见特殊面容和唾液黏稠,均不需特殊喂养。9例父源性15q11.2-q13区域缺失患儿均可见中枢性肌张力低下、皮肤色素减退和哭声微弱,吸吮缓慢2例(22.2%)、需特殊喂养7例(77.8%)、特殊面容5例(55.6%)、男性隐睾7例(77.8%)、阴茎短小4例（44.4%）、女性小阴唇1例(11.1%)、唾液黏稠5例(55.6%)。结论 母源性同源二倍体患儿的特殊面容和男性生殖器发育不全的发生率低于父源性15q11.2-q13区域缺失患儿。新生儿期皮肤色素减退及中枢性肌张力低下是中国PWS新生儿普遍存在的特征,可作为进一步行PWS分子诊断的初步筛选指标。     

腺苷脱氨酶2缺乏症临床特征与基因型分析

目的 总结3例腺苷脱氨酶2 (ADA 2）缺乏症患儿的临床特征及基因型特点,提高对该病的认识。方法回顾性分析3例ADA2缺乏症患儿的临床特点并利用全外显子测序进行遗传学分析。利用试剂盒测定患儿血浆中ADA2酶的活性。总结该病的临床及基因型特征。结果 本组3例患儿均存在ADA2基因变异,例1以反复发热、皮疹、惊厥为主要临床表现,合并脑卒中,伴炎症指标明显升高,ADA2基因存在复合杂合变异：c.139G>T和c.484T>C突变。例2以反复发热、皮疹为主要临床表现,病程中合并消化道穿孔、脑卒中,炎症指标明显升高。WES检测发现ADA2基因存在c.916C>T及c.1069G>A复合杂合突变。例3以反复发热、咳嗽为主要临床表现,合并心肌炎,伴免疫功能明显下降;WES检测发现患者ADA2基因存在c.849T>G纯合突变。血浆ADA2酶活性测定发现例1和2酶活性显著降低。结论 ADA2缺乏症国内罕见,临床特征多变,掌握其临床特征及基因特点,有助于提高诊断水平。     

婴幼儿Prader-Willi综合征2例报告

正Prader-Willi综合征(PWS)又称肌张力低下-智能障碍-性腺发育滞后-肥胖综合征,发病率为1/25000~1/10000[1],是基因组印记的遗传性疾病。现报告收治的2例患儿临床资料,并对其临床和有关的遗传学特点进行分析。1病例资料例1.患儿女,7个月15 d,因反复发热1个月余于2016年4月29日就诊于海南省人民医院。母亲孕1个月时有见红、上呼吸道感染史,孕28周羊水多,     

Prader-Willi综合征46例临床分析

目的探讨新生儿期至青春期Prader-Willi综合征(PWS)患儿的临床特点和诊断方法。方法对2010年1月至2016年1月重庆医科大学附属儿童医院收治的46例PWS患儿临床特点及基因检测结果进行回顾性分析。结果 46例PWS患儿,男28例,女18例,男女比例3∶2。初次就诊年龄0~9岁,确诊年龄14 d至14岁,病程最长达9年。主要临床表现为肌张力低下28例(60%)、喂养困难20例(44%)、哭声低下18例(40%)、智能障碍42例(92%)、肥胖25例(55%)及身材矮小26例(57%)等。各年龄段临床表现不同:新生儿(0~28 d)主要表现为肌张力低下、哭声弱、吸吮力差;婴儿(28 d至1岁)主要表现为运动发育落后、肌张力低下、哭声弱、吸吮力差、特殊面容及皮肤色素减退等;幼儿(1~3岁)主要表现为运动智力发育落后、肌张力低下、皮肤色素减退等;3岁以上患儿出现智力发育落后、食欲亢进及肥胖、身材矮小、外生殖器发育不全。44例为父源性15q11-13区域缺失(96%),2例为母源单亲二倍体(4%)。结论各年龄段PWS患儿临床表现不同,尽早行基因检测有助于早期诊断。     

儿童脾脓肿1 例报告及文献复习

目的总结儿童脓毒症并发脾脓肿的临床特点及治疗。方法回顾分析1例脓毒症并发脾脓肿患儿的临床资料,检索中国知网、万方数据知识服务平台、PubMed中的相关文献并进行总结分析。结果男性患儿,11月龄,以反复发热为主要表现。血培养示屎肠球菌感染,抗感染治疗效果不理想。腹部超声及磁共振成像示脾脏多发脓肿。经超声引导下脓肿抽液后患儿仍发热,最终行脾脓肿切除术。手术1周后患儿体温恢复正常。共检索到国内外相关文献15篇,共59例儿童脓毒症并发脾脓肿病例。临床主要表现为发热、咳嗽、腹痛或腹胀,4例有基础疾病;其中血培养阳性12例,4例为球菌阳性,8例为杆菌阳性。59例患儿均接受抗感染治疗,2例同时行抗结核治疗,1例行脾穿刺,5例行脾切除术。55例患儿预后良好,2例好转,2例病情反复。结论儿童脓毒症并发脾脓肿以发热为主要表现,部分患儿有基础疾病,以足量、足疗程抗感染治疗为主,必要时需行脾脓肿切除术。     

Cryopyrin蛋白相关周期综合征1例报告

目的探讨cryopyrin蛋白相关周期综合征(CAPS)的临床特点及其致病基因。方法回顾性分析1例CAPS患儿的临床表现,实验室检查及基因检测的特点,同时复习相关文献。结果男性患儿,7岁8个月,反复发热7年,全身红色斑片状皮疹,压之可褪色,不伴瘙痒,四肢及关节未见异常;超敏C反应蛋白、红细胞沉降率、类风湿因子升高;眼底动脉硬化,双结膜病变;两侧神经性耳聋。致病基因NLRP3编码区域未见突变,但在5’非编码区发现杂合突变(-2667GT),其NLRP3基因m RNA水平为正常人的4.2倍,IL-1β和IL-18基因表达量也分别升高2.2倍(P=0.002)和1.2倍(P0.05)。结论 CAPS可表现为体温反复升高、皮疹、关节受累,病程进展过程中可出现眼部异常及不同程度的耳聋。NLRP3基因检测有助诊断。     

两性霉素B脂质体治疗婴儿隐球菌性脑膜炎1例

患儿男,3个月,因“反复发热、喘息8d,抽搐1次”于2005-05-11入院。8d前患儿出现发热,体温最高达39.5℃,伴有喘息、咳嗽。曾抽搐1次,表现为双眼上翻,四肢强直,持续约10min,自行缓解,当时体温38.5℃。在当地医院予抗感染治疗,上述症状仍有反复,为进一步诊治入我院。患儿系P1G1,胎     

小儿Prader-Willi综合征1例报告——附临床及遗传学诊断

利用染色体高分辨显带、SNRPN基因甲基化PCR及Southern杂交确诊了 1例Prader-Willi综合征 (PWS)患者。该患儿具有PWS典型症状并伴有糖尿病。通过报道这一病例及复习文献资料 ,分析PWS的临床特征 ,简要讨论其发病机制及遗传学诊断方法。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

�¶�֢��ϵ�ϰ���ע��ȱ�ݶද�ϰ������ڵ�ת��

孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

---

---

Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.