Constrictive amniotic bands,amniotic adhesions,and limb-body wall complex: Discrete disruption sequences with pathogenetic overlap

In a fetopathologic evaluation of 18 cases with amniotic bands, we discerned 3 types of lesions: (1) constrictive tissue bands, (2) amniotic adhesions, and (3) more complex anomaly patterns, designated as limb-body wall complex (LBWC). Constrictive bands are caused by primary amnion rupture with subsequent entanglement of fetal parts (mostly limbs) by shriveled amniotic strands. Adhesive bands are the result of a broad fusion between disrupted fetal parts (mostly cephalic) and an intact amniotic membrane. Most of the craniofacial defects (encephaloceles and/or facial clefts) occurring in these fetuses are not caused by constrictive amniotic bands, but are the result of a vascular disruption sequence with or without cephalo-amniotic adhesion. Our observations confirm the fact that amnion rupture is not a conditio sine qua non for the development of LBWC. However, LBWC is often complicated by rupture of the unsupported amnion with ensuing formation of constrictive bands. We think that the concept that considers the 3 lesions in question as a single pathogenetic entity is erroneous and will inevitably lead to a never-ending debate between followers of the 2 prevailing theories. In our view, the theories of Streeter and Torpin are not mutually exclusive but rather apply to different types of lesions. The recognition of constrictive amniotic bands, amniotic adhesions, and LBWC as discrete but often combined disruption sequences with important pathogenetic overlap may resolve many dilemmas in interpretation when a fetus exhibits classical constrictive bands beside more severe defects.     

羊膜带综合征并发肢体-体腔壁综合畸形尸检及文献复习

目的探讨羊膜带综合征(amnioticbandsyndrome,ABS)的发病机制、临床病理特点与诊断。方法对1例在孕26周经超声检查被诊断为ABS的胎儿病例进行尸检,结合文献讨论其发病机制、临床病理特点及诊断方法。结果本例主要表现为唇裂、腭裂、腹裂、肢体缺陷、脑积水、室间隔肌部缺损、脐带过短等畸形。结论ABS的发病机制存在争议,临床特点呈多样性,肢体-体腔壁综合畸形是其中的严重类型。产科超声检查是诊断胎儿ABS的有效方法。     

Prenatal diagnosis of holoprosencephaly

Holoprosencephaly is a spectrum of congenital defects of forebrain development characterized by incomplete separation of the cerebral hemispheres. In vivo diagnosis can be established with prenatal brain imaging and disease severity correlates with extent of abnormally developed brain tissue. Advances in magnetic resonance imaging (MRI) over the past 25 years and their application to the fetus have enabled diagnosis of holoprosencephaly in utero. Here, we report on the prenatal diagnosis of holoprosencephaly using MRI as part of a diagnostic and management evaluation at a tertiary and quaternary referral center. Using an advanced MRI protocol and a 1.5-Tesla magnet, we show radiographic data diagnostic for the holoprosencephaly spectrum, including alobar, semilobar, lobar, middle interhemispheric, and septopreoptic variant. Accurate prenatal evaluation is important because the severity of imaging findings correlates with postnatal morbidity and mortality in holoprosencephaly. Therefore, this work has implications for the evaluation, diagnosis, management, and genetic counseling that families can receive during a pregnancy.     

OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects) in monozygotic twins

The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is a consistent and recognizable pattern of midline abdominal and pelvic defects. It is rare, affecting 1 in 200,000 to 400,000 pregnancies and is even rarer in twin gestations. This is an autopsy study of OEIS complex in monozygotic twins after pregnancy termination at 20 weeks of gestation. Unremarkable family history but concordance of monozygotic twins for the defects may support the theory that early malformation complexes, e.g., OEIS, and monozygotic twinning are manifestations of the same disturbance of early blastogenesis. Am. J. Med. Genet. 84:29–33, 1999. © 1999 Wiley-Liss, Inc.     

Caudal dysgenesis in staged human embryos: Carnegie stages 16–23

The severity of expression of malformations of the median axis in the caudal region of human embryos is highly variable and ranges from caudal dysgenesis and sirenomelia to simple sacral hypoplasia. Several forms of sacral dysgenesis may be discovered later in life. This shows that caudal malformations of relatively lesser severity should occur at a greater frequency than actually reported. In the present study we looked at the morphology and histology of some human embryos with caudal dysgenesis. Several developmental alterations of the median axis were observed. These included significant reduction in the craniofacial mesenchyme characterized by hypoplasia of the pharyngeal arches, palatal shelves, and agenesis or hypoplasia of the auricular hillocks at the rostral end, absence of the caudal trunk from midsacral to all coccygeal segments, vertebral fusion or agenesis, defective development of the primary and secondary neural tubes, rectal and urinary tract dysgenesis, and deficiency, malrotation, and deficiency of the limbs at the caudal end. Hindlimb malformations included bilateral agenesis (one case), meromelia, and various forms of abnormal rotation, but no instances of sirenomelia were present. Radial dysgenesis has been reported to be associated with caudal dyplasia in the literature, however, we observed agenesis of the ulna in one and of the fibula in another embryo. There was an impressive association between limb malformations and body wall defects. The histological studies demonstrated caudal vascular deficiency and hemorrhagic lesions in the limbs of the dysplastic embryos. The data suggest that these polytopic field defects arise very early in development possibly as result of disturbances to fundamental developmental events that share common molecular and cellular mechanisms. Am. J. Med. Genet. 87:115–127, 1999. © 1999 Wiley-Liss, Inc.     

Complete absence of external genitalia in limb-body wall complex: two cases.

Two neonates with limb-body wall complex (LBWC) and complete absence of the external genitalia are presented. Our patients are the sixth and seventh cases of complete absence of the external genitalia recorded in English publications and the first two cases associated with LBWC. The incidence of complete absence of the external genitalia in our newborn population during a period of 12 years (1975 to 1986) was one case per 13 420 births.     

Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature

Complex chromosome rearrangements (CCR) are rare structural rearrangements. Currently six cases of prenatally diagnosed balanced de novo CCR have been described. We present two new cases of prenatally ascertained balanced de novo CCR. In the first case, an amniocentesis revealed a balanced de novo three-way CCR involving chromosomes 5, 6, and 11 with a pericentric inversion of chromosome 5 [four breaks]. In the second case, a balanced de novo rearrangement was identified by amniocentesis which involved a reciprocal translocation between chromosomes 3 and 8 and a CCR involving chromosomes 6, 7, and 18 [six breaks]. The use of whole chromosome painting helped elucidate the nature of these rearrangements. A review of the postnatally ascertained cases suggests that most patients have congenital anomalies, minor anomalies, and/or developmental delay/mental retardation. In addition, there appears to be a relationship between the number of chromosome breaks and the extent of phenotypic effects. The paucity of information regarding prenatally diagnosed CCR and the bias of ascertainment of postnatal CCR cases poses a problem in counseling families. © 1996 Wiley-Liss, Inc.     

The heritability of intelligence in Japan

Japanese data for 543 monozygotic (MZ) twins and 134 dizygotic (DZ) twins tested for intelligence at the age of 12 give correlation coefficients of. 782 and .491, respectively, indicating a heritability of .582. Heavier twins at birth have significantly higher IQs at the age of 12, suggesting that prenatal nutrition exerts a significant effect on intelligence.     

山西省出生缺陷高发区重大体表出生缺陷的流行状况研究

目的了解山西省出生缺陷高发地区目前各种体表出生缺陷患病水平及流行特征.方法以人群为基础对山西省的4个县24种体表重大出生缺陷进行监测.结果 2003年四个县共监测到孕满20周以上的出生11534名,总出生缺陷患病率分别为232.4/万.神经管畸形患病率为138.7/万,占全部出生缺陷病例的59.7%.患病率高于10/万的出生缺陷有7种,依次为:无脑儿(65.9/万)、脊柱裂(58.1/万)、脑积水(47.7/万)、多指(26.0/万)、腭裂(21.7/万)、脑膨出(14.7/万)、唇裂(10.4/万).产妇文化程度低和女性胎婴神经管畸形的患病率显著增高.此外,居住在农村,妇女年龄不足20岁或30岁以上神经管畸形患病率有升高的趋势.结论神经管畸形仍然为山西省出生缺陷高发区最常见的先天畸形,目前其患病率仍然处于我国乃至世界最高的水平.居住在农村、文化程度低、怀孕年龄太小或较大的妇女生育出生缺陷儿的危险性较大.     

结节性硬化症家系的基因诊断及产前诊断

目的 对结节性硬化症(tuberous sclerosis complex,TSC)患者进行基因突变检测,并在基因诊断结果明确的基础上应用于产前诊断.方法 应用聚合酶链反应-变性高效液相色谱(polymerase chain reaction-denaturing high-performance liquid chromatography,PCR-DHPLC)、DNA测序技术,对19个家系的21例TSC患者进行TSC1和TSC2基因的突变检测.结果 在19个家系21例患者中发现17种不同的基因突变,其中13种突变未见报道,包括TSCj基因的c.2672delA、c.2672insA和TSC2基因的c.4918insCGCC、c.1143delG、Intron27+1 G＞A、c.1957-1958delAG、Intron5+1 G＞A、c.910insCT、c.2753C＞G、c.4078dupAGCAAGTCCAGCTCCTC、Intron 11-1 G＞A、Intron 14+1 G＞A、c.684 C＞A.对7个家系进行了产前诊断,其中6个家系的胎儿均未发现其家系先证者所具有的突变,胎儿出生后电话随访至1～4岁无TSC的症状出现.而另一家系的胎儿携带有和母亲一样的突变,经遗传咨询后,家属选择了引产.结论 本研究证实的TSC基因突变中,有76.5%(13/17)的突变均未在其他研究中被发现,说明中国人群TSC基因的突变谱可能与其他人群具有较明显的差异;本研究中TSC基因诊断率为89.5%(17/19),提示TSC的发生可能还有其它未知的遗传病因;在有家族史的病例中,TSC1与TSC2有相似的突变比例,而在散发病例中,TSC2的突变更加常见;13种新突变患者的父母均无类似突变,说明TSC致病基因具有较高的自发突变率.     

基于社区水平的珠海市大人群地中海贫血的遗传筛查和产前诊断

目的 阐述在广东省珠海市开展基于社区的控制重型α和β地中海贫血(简称地贫)的预防模式.方法 构建由6家医院组成的二级地贫遗传服务网络,以珠海市婚前医学或产前检查人群作为筛查对象,采用常规杂合子筛查策略,以标准的血液学分析流程进行α和β地贫特征的筛查.对所有地贫疑诊对象进行随访和遗传咨询,并采用基于PCR的分子诊断技术对高风险夫妇进行确诊.在知情同意和选择的情况下,对高风险妊娠实施产前基因诊断并通过选择性引产淘汰受累的重型地贫胎儿.结果 从1998年1月至2005年12月,共筛查了85522例拟婚育龄青年和10439例孕妇,婚检地贫筛查覆盖率达到71.38%.在6563例地贫筛查阳性的病例中,α和β地贫分别为4312例(4.5%)和2251例(2.3%);总计发现148对有生育重型地贫儿可能的高风险夫妇(α地贫103对,β地贫45对),其中有142对(95.9%)高风险夫妇进行了产前诊断(α地贫98例,β地贫44例).本项目启动后共减少了41例重型地贫患儿的出生,其中包括Hb Barts水肿胎23例、Hb H病4例和重型β-地贫14例.结论 这是我国首次基于社区水平的、在拥有129万人口的珠海市实施的前瞻性α和β地贫预防监控计划.这一预防模式对我国其他地贫高发区和其他发展中国家开展地贫和其他血红蛋白病的预防有着重要的借鉴意义.     

The femur, fibula, ulna (FFU) complex in siblings

Two siblings affected with the Femur, Fibula, Ulna (FFU) complex are reported. The FFU complex is relatively common, but was not previously reported in relatives.     

Cardiovascular malformations: Changes in prevalence and birth status, 1972–1990

Through an ongoing hospital-based active malformation surveillance program, we identified cardiovascular malformations (CVMs) in 3.3 per 1,000 liveborn and stillborn infants, and fetuses from pregnancies terminated electively during a 15-year period. We excluded the children of mothers who had planned delivery elsewhere, but were transferred for care of anomalies that had been detected in prenatal screening. Birth status changed markedly during the study with a significant increase in elective terminations of fetuses with a CVM from 0 to 22% (P < 0.01 based on a test for trend). The proportion of liveborn infants with CVMs decreased from 90% to 73% (P < 0.01); the frequency of stillbirths did not change. During the study period, there was a significant increase in the prevalence of CVMs in all births (P < 0.01) and elective terminations (P < 0.01). The increase in liveborn prevalence was not statistically significant (P = 0.08). Stillborn prevalence was unchanged. The number of mothers having prenatal ultrasonography (P < 0.01 for trend) and amniocentesis (P < 0.01 for trend) increased steadily. There were significant increases in the proportion of mothers having any ultrasound examination (P < 0.01 for trend), the number of initial ultrasound examinations occurring in the second trimester (P < 0.01 for trend), and the proportion of mothers having amniocentesis (P < 0.01 for trend). There was a significant increasing trend in the proportion of mothers who were 35 years and older (10% in 1972–1974, 26% in 1988–1990, P < 0.01). This hospital-based active surveillance program suggests that more frequent elective terminations had a significant effect on overall birth prevalence of CVMs. This trend would not have been detected by most other surveillance systems which determine prevalence of common birth defects from birth certificates and other forms of administrative reporting, and exclude elective terminations of pregnancy. Am. J. Med. Genet. 84:102–110, 1999. © 1999 Wiley-Liss, Inc.     

铅汞等重金属元素与神经系统畸形发生的关系研究

目的探讨铅、汞、砷、镉、锰、锌与人类胎儿神经系统畸形的关系。方法收集2006年9月至2007年7月期间在上海市第一妇婴保健院产前检查中发现的52例胎儿神经系统畸形孕妇作为病例组,以同期该医院内204例正常孕妇为对照组。问卷调查与神经系统畸形发生可能相关的社会环境因素。采用微波消解和质谱分析方法测定孕妇全血中铅、砷、镉含量以及血清锰、锌含量。全血汞含量利用原子吸收法测定。结果孕妇职业暴露、居所附近存在工厂以及被动吸烟与神经系统畸形发生呈正相关,孕妇文化水平,叶酸与畸形发生呈负相关。在校正这些因素的影响后,logistic回归分析仍提示血铅为神经系统畸形的危险因素,其OR值为1.039,95%CI为1.015-1.065,血锌作为保护性因素,其OR值为0.998,95%CI为0.996-0.999。结论孕妇工作和居所环境以及被动吸烟与神经系统畸形发生有关。孕妇文化水平、叶酸和锌是防止神经系统畸形发生的保护性因素,而铅暴露可能是神经系统畸形发生的重要原因之一。     

Combination of elevated maternal serum alpha-fetoprotein (MSAFP) and low estriol is highly predictive of anencephaly

Increased levels of second trimester maternal serum alpha-fetoprotein (MSAFP) have long been established as a marker for neural tube defects (NTDs). In addition, decreased levels of maternal estriol in the third trimester have been reported in pregnancies with anencephalic fetuses. The purpose of this study was to evaluate whether early second trimester unconjugated serum estriol (uE3) is an independent predictor of NTDs. The study included 57,031 patients who underwent maternal serum screening with MSAFP at 14–22 weeks gestation. Of these, 23,415 also had uE3 measurements. There were 63 cases of NTD, an overall incidence of 1.1 per 1,000. Elevated MSAFP (≥2.5 MOM) was detected in 1,346 patients, 48 of which had NTDs. Decreased uE3 (≤0.5) was detected in 1,437 patients, 17 of which had NTDs. The incidence of NTDs was significantly higher in patients with low uE3, compared to patients with normal/high uE3 (1.15% vs. 0.09%, P < 001). Finally, 51 patients had both increased MSAFP and decreased uE3; 16 of these had NTDs, 14 of which were anencephalics. In conclusion, both elevated MSAFP and low maternal serum estriol are predictive of NTD but have a low sensitivity. The combination of abnormally elevated MSAFP and low estriol is highly predictive of NTD in particular anencephaly. Am. J. Med. Genet. 75:297–299, 1998. © 1998 Wiley-Liss, Inc.     

Equipoise of recent estimated Down syndrome live births in Japan

To support people with Down syndrome (DS), it is essential to know and predict the number of live births of children with this condition. In this study, we estimated DS live birth rates on the basis of maternal age distribution and numbers of births in the general population, the maternal‐age specific chance for a live birth of a child with DS, and the prenatal diagnosis/termination rate. The total number of live births in Japan decreased to less than 1 million in 2016 and the percentage of women aged 35 years old or over giving birth has increased by sixfold. Prenatal genetic testing in Japan has gradually become more widespread, and 20% of all cases of DS were diagnosed prenatally in 2016. Meanwhile, the annual projected number of DS live births has remained steady at around 2,200 (22 per 10,000 births). In 2016, it was estimated that 70% of all DS babies were born to women of advanced maternal age (AMA). Given that Japan is facing a decreasing birth rate and an aging population, adoption of the practice of prenatal genetic testing for AMA has balanced the number of DS births over the last 7 years from 2010.     

Experimental assay of a Dual Mesh polytetrafluoroethylene prosthesis (non-porous on one side) in the repair of abdominal wall defects

The porosity of the prosthetic biomaterials used to repair defects in the abdominal wall seems to influence the tissue repair process insofar as tissue integration of the prosthetic material and the formation of adhesions with abdominal viscera are concerned. We studied the behaviour of a new type of polytetrafluoroethylene prosthesis used for the repair of abdominal wall defects, Dual Mesh^® (DM), which has two different faces; one face has a porosity between 30 and 60 μm, while the other is nonporous. In 20 New Zealand White rabbits, a full-thickness (except skin) 7cm × 5cm defect was created in the anterior abdominal wall that was repaired with DM. At 14, 30, 60 and 90 days, samples were obtained and studied by light and scanning electron microscopy. An immunohistochemical study was made with antibody anti-rabbit macrophages (RAM-11). Tensile strength was measured with an Instron tensiometer using 2-cm-wide strips obtained parallel to the shorter axis of the implant. DM induced little tissue adhesion to the material on the visceral peritoneum interface and was surrounded by organized repair tissue. The biomaterial was integrated in the repair tissue on the subcutaneous interface, but not on the peritoneal interface. The macrophage response decreased between days 14 and 90 (P < 0.001). Tensile strength increased significantly (P < 0.05) at every study period. We conclude that the DM prosthesis has little tendency to formation of visceral adhesions, the DM prosthesis was well tolerated by the receptor organism and the tensile strength of the prosthesis/ receptor tissue interface increased with time.