基于亚低温床垫与高压氧舱结合的新生儿智能调控系统——一种发明专利的介绍

儿童神经发育障碍（neurodevelopmental disorders, NDDs）是由多种遗传性或获得性病因导致的一组慢性发育性脑功能障碍疾病,主要包括智力发育障碍、发育性言语或语言障碍、孤独症谱系障碍、发育性学习障碍、注意缺陷多动障碍、抽动障碍和其他神经发育障碍等。随着NDDs研究水平和诊治技术的提高,儿童NDDs研究取得了很大进步。为进一步提高儿科医生对儿童NDDs认识的广度和深度,该文就儿童NDDs研究进展作一综述。     

46,XY性发育异常的内分泌评估及治疗

46,XY DSD是指染色体核型为46,XY但性腺性别和(或)表型性别与之不相匹配的一类先天性异常疾病。由于该病是一系列难以归类、难以诊断的复杂性疾病,具有高度的遗传异质性,个体间临床表现差异较大,因此其临床诊治困难。任何影响睾丸分化、睾酮合成或作用的因素都可导致46,XY DSD的形成。在临床工作中,应综合考虑患儿外生殖器评估情况、影像学检查(B超及核磁)结果、性腺轴及垂体其他轴系功能评估结果(儿童特殊阶段依赖和选择好适当的激发试验)对不同病因进行鉴别诊断。基因检测虽然可以对明确诊断起到至关重要的作用,但必须通过临床表现解释其致病性。恰当的治疗需要内分泌科、泌尿外科、整形外科、医学心理科、遗传学科等多学科共同参与合作。     

孤独症谱系障碍动物模型的研究进展

孤独症谱系障碍是一种神经发育障碍性疾病。其病因多样,多数认为是环境与遗传的共同结果。动物模型,作为孤独症谱系障碍疾病的研究工具,通过生化作用诱导与基因分子缺陷,从而获得不同的孤独症动物亚型,以研究孤独症的病因,行为学表型,探索药物及干预疗法的安全性和有效性,以期提高孤独症个体的生活质量。     

单纯性生长激素缺乏症的遗传学病因研究进展

单纯性生长激素缺乏症(isolated growth hormone deficiency, IGHD)是以身材矮小为特点的一种生长发育障碍性疾病。IGHD的病因及发病机制仍不完全明确, 先天性[遗传和(或)与畸形有关]或获得性(肿瘤、身体创伤、炎症、脑部感染或放射治疗)因素均可导致IGHD。在其遗传病因中最常见的基因突变发生在编码生长激素(GH1)和生长激素释放激素受体(GHRHR)的基因。罕见情况下转录因子(如HESX1、SOX3、OTX2、POU1F1等)突变可以导致IGHD, IGHD相关基因突变的疾病表型高度可变。近年来有关IGHD致病基因的研究在不断增加, 正确诊断及尽早治疗对于IGHD患者的长期预后至关重要。该文综述了近年来IGHD的基因突变、疾病表型等方面的研究进展。     

孤独症谱系障碍的多学科合作研究与干预

孤独症谱系障碍（autism spectrum disorder,ASD）是一组临床异质性高的神经发育障碍性疾病,常伴有共患病,其病因尚不明确,终身致残率高,可致儿童、青少年和成人在社交、认知和语言发展以及适应性功能等多个方面的障碍;在研究和干预中多学科（multidisciplinary）合作是新趋势,以从不同层面探究病因机制和临床转化;并提倡集合不同专业背景的人员对ASD患者及其家庭进行帮助,对临床诊断、教育、健康和社会关怀等方面的决策制定提供支持。     

儿童淋巴瘤与淋巴细胞性白血病的鉴别诊断与治疗差异

儿童淋巴系统恶性肿瘤主要包括急性淋巴细胞性白血病（ALL）和淋巴瘤。ALL可发生类似淋巴瘤的局部浸润,而淋巴瘤易发生类似ALL样的骨髓转移,因此给临床医师的诊断和治疗造成了一定的难度,现从淋巴细胞的不同发育成熟阶段恶性转化后形成的不同临床类型肿瘤的角度出发,讨论其相应的形态、免疫表型和融合基因特征及二者的鉴别诊断及相应的治疗差异。     

小儿阴茎发育障碍的诊断与治疗

小儿阴茎发育障碍在临床上可分两类,一是多系先天性且伴性激素水平异常的真正的小阴茎,二是多因伴发畸形或后天因素影响但无性激素及染色体等异常之阴茎发育不良.因小儿阴茎大小随年龄大小、个体差异等不同而变化,故在临床上欲作出阴茎发育是否正常的判断,以及明确病因、制定有效的治疗方案常感困难.     

儿童支气管哮喘的诊断进展——2008 PRACTALL解读

5岁及以下儿童哮喘的诊断极为困难,因为诊断只能依靠临床判断、症状评价和体征分析。PRACTALL共识报告特别针对儿童哮喘制定,在诊断中强调了儿童哮喘的自然病史和病理生理特点、儿童喘息的不同类型、儿童哮喘的不同临床表型等,并推荐了不同年龄儿童哮喘的诊断、临床管理及监测的方法;强调诊断需要综合考虑,包括反复喘息的类型、特异体质病史、哮喘危险因素、长期随访、广泛鉴别诊断和观察对支气管舒张剂及抗炎治疗的反应。     

胎粪性腹膜炎23例临床分析

目的：　探讨胎粪性腹膜炎的病因、临床特点及诊断治疗。方法：　采用回顾性研究,通过对23例患者的临床分析,结合X线检查,来阐明其特点,并对其治疗进行分析。结果：　胎粪性腹膜炎的病因以肠闭锁多见,占30.4% (7/23);其临床特征主要为:腹腔内钙化,大量纤维组织粘连,伴或不伴有假性囊肿形成;手术治疗是有效的治疗方法。结论：　肠闭锁是胎粪性腹膜炎的重要原因;早期诊断,正确的手术方式,认真的术后护理是提高胎粪性腹膜炎存活率的关键     

单纯性血尿病因诊断分析

报告１２３例儿童单纯性血尿临床和病理资料分析。结果表明，单纯性血尿在小儿泌尿系疾病中占有重要地位（占１９．２％）。１２３例中单因肾性血尿４６例（占３７．４％），单因非肾性血尿６７例（占５４５％），两种病因并存者１０例。系膜增生性肾炎，薄基底膜病和轻微病变是肾性血尿的主要病因；特发性高钙尿症和“感冒通”所致的药物性血尿是非肾性血尿的主要病因。提示肾活检电镜检查在行性血尿病因诊断中及尿钙测定在单纯性血尿病因诊断中均有重要意义。     

Management of children with disorders of sex development: 20-year experience in southern Thailand

Background

Disorders of sex development (DSD) is a group of sexual differentiation disorders resulting in genital anomalies with defects in gonadal hormone synthesis and/or incomplete genital development. These conditions result in problems concerning the sex assignment of the child. This study aims to describe the clinical features, diagnosis and management of children with DSD in southern Thailand.

Methods

The medical records of 117 pediatric patients diagnosed with DSD during the period of 1991–2011 were retrospectively reviewed.

Results

Disorders of sex development were categorized into 3 groups: sex chromosome abnormalities (53.0%), 46,XX DSD (29.9%) and 46,XY DSD (17.1%). The two most common etiologies of DSD were Turner syndrome (36.8%) and congenital adrenal hyperplasia (29.9%). Ambiguous genitalia/intersex was the main problem in 46,XX DSD (94%) and 46,XY DSD (100%). Sex reassignment was done in 5 children (4.3%) at age of 3–5 years: from male to female in 4 children (1 patient with congenital adrenal hyperplasia, 1 patient with 45,X/46,XY DSD, and 2 patients with 46,XX ovotesticular DSD) and from female to male in 1 patient with 46,XX ovotesticular DSD. Of the total 20 children with 46,XY DSD, 16 (80%) were raised as females.

Conclusion

Management of DSD children has many aspects of concern. Sex assignment/reassignment depends on the phenotype (phallus size) of the external genitalia rather than the sex chromosome.     

性发育异常新生儿的临床评价和管理

性发育异常/性分化异常（DSD）是患儿染色体核型与性腺表型和（或）性腺的解剖结构不一致,表现为新生儿性别难辨。DSD主要根据染色体核型分为3类：46,XY DSD、46,XX DSD、性染色体DSD。临床上需要结合病史、体格检查、实验室和影像学检查来进行新生儿DSD的诊断、综合评估以及明确潜在的病因。性别认定必须在所有诊断评估完成后才能做出。医学社会多因素包括基因型性别（核型）、激素性性别（睾酮、双氢睾酮、肾上腺类固醇系列激素水平）、表现型性别（内外生殖器的外观）、生殖性别（生育的潜能）和父母的感觉乃至社会接受程度和宗教习俗等都会影响DSD患儿的性别认定。一个多学科合作的团队是必需的,患儿家人必须参与到有关性别认定的所有过程中。新生儿医师对于DSD 的主要任务在于评估患儿状况及其管理。     

Disorders of gonadal development: a broad clinical, cytogenetic and histopathologic spectrum

The most complicated group of sexual differentiation disorders is that of gonadal development. Disorders of gonadal development form a wide clinical, cytogenetic and histopathological spectrum. There are still some unsolved difficulties of diagnosis, development of malignancy and the sex rearing of these patients. We reviewed 23 cases of gonadal developmental disorders among 169 patients with ambiguous genitalia or delayed puberty. Among 169 patients, 87 patients were 46,XY disorders of sex development (DSD), 59 patients were 46,XX DSD without disorders of gonadal development and the remaining 23 patients had disorders of gonadal development. Nine of these 23 patients were diagnosed as 46,XY gonadal dysgenesis, 7 patients had ovotesticular DSD, 5 patients had 45,X/46,XY mixed gonadal dysgenesis. Fourteen patients with disorders of gonadal development had genital ambiguity, 5 patients had a female genital phenotype with a palpable gonad and/or delayed puberty. Four patients had the male genital phenotype. Disorder of gonadal development is a very important clinical problem with different aspects of diagnosis, treatment, rearing sex and prophylaxis. Each patient should be evaluated individually employing a multidiciplinary approach.     

Update on the management of disorders of sex development

A number of factors have contributed to a sharp increase in the number of publications related to disorders of sex development (DSD) in the past 5 years, namely: the establishment of a consensus in 2006 about nomenclature, investigations and the need to treat these patients in a multidisciplinary setting; increase of the knowledge base about genetic mechanisms of normal and abnormal sex development; critical appraisal about the timing and nature of genital surgery in patients with DSD. Herein, the authors present a comprehensive review with up-to-date data about the approach to the newborn with ambiguous genitalia as well as the diagnosis and management of the most common DSD.     

46, XY 性发育障碍儿童 NR5A1 基因突变 1 例报告及文献复习

目的探讨NR5A1基因突变导致的46,XY性发育障碍(DSD)的临床表现和分子诊断。方法回顾分析1例社会性别为女性的46,XY DSD患儿的临床资料,并复习相关文献。结果社会性别为女性的11.5岁患儿,因偶然发现阴蒂肥大半个月就诊;初步系列实验室检查诊断考虑支持46,XY DSD,高促性腺激素性发育不良。全基因组外显子组DNA测序提示NR5A1基因,c.937 CT,p.Arg313Cys杂合突变;母亲为杂合突变携带者,父亲无异常。结论临床表现为46,XY DSD,性腺发育不良、外生殖器女性化合并肾上腺功能不足;提示存在SF1基因突变的可能性,全基因组外显子基因测序可帮助明确诊断。     

The impact of culture on disclosure in differences of sex development

Differences of sex development (DSD) include a variety of complex congenital genitourinary abnormalities–whether sporadic or hereditary. The 2006 DSD Consensus Statement and 2016 Update Consensus Statement encourage better communication among providers, between providers and parents, as well as among providers, parents, and patients when developmentally appropriate.^1,2 However, a lack of clear communication about the diagnosis and its sequelae may occur at three levels: (1) disclosure from DSD patients’ families to their physician, (2) disclosure from patients to their families/communities, and (3) disclosure from the physician to the DSD patient. Additionally, there is a paucity of research available on how culture can impact disclosure among individuals with DSDs. This article discusses disclosure among the various stakeholders and briefly explores the impact of cultural expectations and beliefs with regards to disclosure.     

Laparoscopy versus ultrasonography for the evaluation of Mullerian structures in children with complex disorders of sex development

Purpose

The diagnosis of children with disorders of sex development (DSD) requires a karyotype, different biochemical and radiological investigations in the context of a multidisciplinary team. The aim of this study was to compare the diagnostic accuracy of laparoscopy (L) versus ultrasonography (US) in the assessment of children with complex DSD.

Methods

We retrospectively examined the theatre database searching for children with DSD who underwent laparoscopic surgery from 1999 to 2011. The medical and radiological records were reviewed.

Results

Eighteen patients were identified. Age at diagnosis ranged from birth to 14?years (mean 2.5?years). There were seven patients with 46XY dysgenetic testicular DSD (4 mosaic Turner, 3 mixed gonadal dysgenesis), seven patients with 46XY non-dysgenetic testicular DSD (4 persistent Mullerian duct syndrome, 2 complete androgen insensitivity syndrome, one unknown), two patients with ovotesticular DSD, one patient with 46XX DSD (congenital adrenal hyperplasia) and one patient with 46XY DSD complete sex reversal. Fifteen underwent ultrasonography prior to laparoscopy. Both modalities identified Mullerian structures in seven (47?%) patients, in one (7?%) patient US and L confirmed the absence of Mullerian structures, while in six (40?%) patients there was discordance, with US failing to visualize pelvic Mullerian structures. In the last patient with 46XY non-dysgenetic testicular DSD, the rectum was thought to be a dilated uterus on ultrasonography.

Conclusions

Pelvic ultrasonography failed to identify Mullerian structures in 40?% of patients with complex DSD. On the contrary, laparoscopy allowed excellent visualization of pelvic structures and gonads in children with complex DSD.     

病因不明性发育异常患儿153例临床及身高状况分析

目的 分析病因不明性发育异常（DSD）患儿的类型分布、临床特征及身高情况。方法 选取病因不明DSD患儿，采集临床资料，检查骨龄、染色体，行性腺、盆腔及腹部B超检查，HCG试验，评估DSD的临床类型，评价身高发育状况。结果 153例病因不明DSD患儿纳入分析，其中初诊时社会性别男128例，女25例，平均年龄（4.6±4.2）岁（42 d至16岁10个月），3岁前就诊者87例（56.9%）。有DSD家族史者15例（9.8%）。母亲孕期使用孕酮类保胎药19例（12.4%）。①134例行染色体检查，其中46，XY DSD 121例（90.3%），46，XX DSD 3例（2.2%），性染色体异常DSD 10例（7.5%）。121例46，XY DSD 中，主要为小阴茎合并尿道下裂39例（32.2%），小阴茎合并睾丸异常19例（15.7%），单纯小阴茎18例（14.9%）。②46，XY DSD患儿中身高小于2005年中国2～18岁儿童青少年身高百分位数值表（简称身高数值表）P25者46例（38.0%），与正常儿童比较差异有统计学意义（P=0.039）；身高小于身高数值表P50者76例（62.8%）。10例性染色体异常DSD患儿中，身高小于身高数值表P25者5例。③卵巢/睾丸发育异常（双向性腺）DSD患儿8例，其中46，XY 3例，46，XX 2例，嵌合染色体3例。身高小于身高数值表P25和P50者分别有5例（62.5%）和7例（87.5%）。 ④125例进行了HCG激发试验，其中HCG标准试验反应良好78例，HCG延长试验反应良好14例，HCG试验反应不良33例，3组身高小于身高数值表P50者分别为31例（39.7%）、11例（78.6%）和27例（81.8%），差异有统计学意义（P=0.000）。结论 本组病因不明DSD患儿以46，XY DSD为主。46，XY DSD患儿以各类小阴茎表现最多见。DSD家族史和母孕期服用保胎药可能是DSD的原因之一。DSD患儿身高小于身高数值表P25及P50的比例高于正常儿童。DSD患儿的身高与睾丸发育状况、HCG反应有明显关系，提示DSD患儿的身高受损与睾酮产生能力有关。     

Zur Stellungnahme des Deutschen Ethikrates zu Besonderheiten der Geschlechtsentwicklung (Intersexualität)

Disorders of sex development (DSD) represent a heterogeneous group of rare to very rare congenital abnormalities of chromosomal, gonadal and phenotypic sex which affect the urogenital tract and the endocrine-reproductive system. In this context some affected persons employ the term intersexuality which was also previously applied in medical areas in order to indicate the deviation from the normal gender also in a social context. In February 2012 the German Ethical Committee published an extensive statement dealing with the legal, social and medical aspects of intersexuality/DSD. In this article a summary of this statement will be presented and the resulting consequences in the context of a pediatric perspective will be discussed. The German Society for Pediatric Endocrinology and Diabetology (DGKED) explicitly supports the standpoint of the Ethical Committee and with this article would like to build the foundations for a more encompassing future consensus for the treatment of DSD and dealing with intersexuality.     

卵睾型性发育异常单中心临床诊治分析

目的 总结卵睾型性发育异常的临床特点及诊治经验.方法 回顾性分析1993年1月至2015年12月就诊于医院并通过病理确诊卵睾型性发育异常的32例患儿临床资料和随访资料.社会性别:男30例,女2例.12.5％呈女性外貌,生殖器类别模糊,阴蒂1～3 cm,小阴唇发育差,有乳房发育;87.5％呈男性外貌,阴茎发育极差,重度下弯,尿道开口异常(位于阴囊处或会阴部),阴囊不同程度女性化,外形近阴唇貌,其中46.9％(15/32)伴有隐睾.染色体核型分析:46,XX卵睾型DSD 11例;46,XY卵睾型DSD 1例;性染色体异常DSD中的卵睾型性发育异常20例(嵌合性46,XY/46,XX6例;混合型14例).结果 11例行泌尿生殖系彩超和排泄性尿道阴道造影,二者结合检出率为100％(11/11).5例行SYR基因筛查,1例45,X卵睾型DSD及1例45,X/46,XY卵睾型DSD为SYR阳性,1例45,X/46,XY SYR基因为阴性,余2例46,XX卵睾型DSD中,50％SYR基因为阴性.64个性腺中16个卵睾,25个睾丸,23个卵巢.性腺畸形:双侧型5例,单侧型6例,片侧型21例.30例按男性抚养者均完成阴茎矫直术和尿道重建术.对29例患儿进行8个月～9年的随访,其中3例术后反复发生尿瘘,多次行尿瘘修补术,阴茎及睾丸发育极差,生活质量差;4例术后尿道开口位于冠状沟部或阴茎体部,排尿可;3例进入青春期后有乳房发育;2例阴茎、睾丸发育稍差;余阴茎形态可,长2.5～4.0 cm,睾丸测值较同龄人稍小.2例按女性抚养者均完成阴蒂矫形术,均获得满意的外观,1例处于青春期发育阶段,另1例予雌激素替代治疗后获得青春期发育,外阴形态可,有乳房发育.结论 早期诊断,确诊后是否立刻性别选择行手术治疗仍有争议,我们认为应将患儿的心理性别、社会性别作为参考的首要标准结合激素水平评估、优势性腺评估最后选择性腺切除或重建手术并辅以激素治疗.对于维持患儿正常的性生理、性心理及社会生活具有重要的意义.