Prenatal diagnosis of 48,XYY, +21 ascertained through ultrasound anomalies.

During a routine ultrasound study on a fetus at 21 weeks, nuchal edema was noted. At 21 weeks, repeat ultrasound study at our unit showed scalp and neck edema and a femur length/biparietal diameter ratio below the mean. Transabdominal chorionic villus sampling identified a 48.XYY, +21 chromosome constitution. The fetus had normal internal/external genitalia and signs of Down syndrome.     

Lissencephaly type III, stippled epiphyses and loose, thick skin: a new recessively inherited syndrome

We report on two new cases of syndromic lissencephaly in two consanguineous sibs, with skeletal abnormality, born to young, healthy, second cousin parents with healthy children. In Case 1, fetal ultrasound screening at 32 weeks of gestation showed microcephaly, skin infiltration and equinovarus feet. MRI disclosed cerebral agyria, hypoplastic cerebral mantle and posterior agenesis of the corpus callosum. The propositus, a boy, died soon after birth at term. In Case 2, fetal ultrasound study performed at 16 weeks of gestation disclosed skin infiltration. MRI at 22 weeks of gestation showed microcephaly with agenesis of corpus callosum and cerebellar hypoplasia. Pregnancy was terminated at 22 weeks of gestation. The fetus had normal 46, XY karyotype and similar anomalies found in the index case, with cranio-facial edema and arthrogryposis. X-ray films showed epiphyseal stippling of cervical vertebrae, feet and sacrum. Metacarpal bones were shortened with hypoplastic distal phalanges. Neuropathological findings were concordant with the pattern described in type III lissencephaly: an agyric brain with hypoplastic brain stem and cerebellum, severe neuronal loss of the cortical plate, matrix zone, basal ganglia, brainstem nuclei and spinal cord with axonal swelling and microcalcification. This entity seems to be a new syndromic lissencephaly type III, because of epiphyseal calcifications and metacarpophalangeal bone dysplasia. Copyright Wiley-Liss. Inc.     

Autopsy,radiographic, and prenatal ultrasonographic examination of a stillborn fetus with femoral facial syndrome

Femoral facial syndrome (FFS) is comprised of cleft palate, micrognathia, short or absent femora, and vertebral and genitourinary malformations. We report on a stillborn fetus with FFS delivered to a mother with gestational diabetes. Prenatal ultrasound examination showed abnormalities at 21 weeks of gestation; prior ultrasound findings were interpreted as normal. Long bone histology showed disorganization of the growth plate with a relative decrease in cartilaginous matrix and vacuolization and binucleation of the chondrocytes. Am. J. Med. Genet. 71:76–79, 1997. © 1997 Wiley-Liss, Inc.     

Apparent normalisation of fetal renal size in autosomal dominant polycystic kidney disease (PKD1)

We present a family with adult onset autosomal dominant polycystic kidney disease (ADPKD) in two generations, linked to the PKD1 locus and with paternal transmission to the fetus. The fetus carried the PKD1 haplotype and was, therefore a gene carrier. Progressive hyperechogenic renal enlargement, but no cysts, was documented by serial fetal ultrasounds at 21, 23 and 34 weeks of gestation. Surprisingly, the newborn renal scan showed normal sized kidneys with apparently normal corticomedullary differentiation. However, at 11 months of age, the evolution of cysts in one kidney, and then in the other kidney at 20 months, was documented by ultrasound in the absence of clinical symptoms or signs. The observed normalisation of fetal renal ultrasound appearances at birth has not previously been described in fetuses presenting with PKD1.     

First-trimester diagnosis of Blomstrand lethal osteochondrodysplasia

Blomstrand chondrodysplasia is a rare lethal skeletal dysplasia with presumed autosomal-recessive inheritance. A family with 2 affected fetuses was studied. One fetus demonstrated a severe skeletal dysplasia at routine transabdominal ultrasound examination at 18.5 weeks of gestation. The pregnancy was terminated and the diagnosis of Blomstrand chondrodysplasia was made at autopsy. A second affected fetus was identified by first-trimester transvaginal ultrasound at 12 weeks of gestation. In this case the diagnosis was confirmed by posttermination radiography and histopathology. From these observations, Blomstrand chondrodysplasia seems like a lethal rhizo/mesomelic short-limb, early-onset dysplasia with autosomal-recessive inheritance. Easy detectability by transvaginal ultrasound is demonstrated, but general applicability awaits further studies on the intra- and interfamilial variability of this disorder. Am. J. Med. Genet. 73:345–350, 1997. © 1997 Wiley-Liss, Inc.     

Recurrence of achondrogenesis type II within the same family: evidence for germline mosaicism

Achondrogenesis type II is a lethal skeletal dysplasia caused by new dominant mutations within the type II collagen gene (COL2A1). Here we report on two pregnancies of a healthy, nonconsanguineous young couple. In the first pregnancy, severe micromelia and generalized edema were noted on ultrasound at 21 weeks' gestation. Clinical, radiological, and histological evaluation of the fetus after termination of the pregnancy showed typical findings of achondrogenesis type II. In the second pregnancy, fetal hygroma was noted at 11 weeks' gestation. Similar clinical, radiographic, and histologic findings were observed in the second fetus, suggesting the recurrence of achondrogenesis II within this family. Molecular analysis of genomic DNA extracted from amniotic cells of the second fetus revealed heterozygosity for a 1340G > A missense mutation (G316D) in the COL2A1 gene. This mutation was not found in the parents. Although, we could not evaluate the presence of this mutation in the first fetus, we strongly believe that our data are in favor of germline mosaicism as the most likely explanation for the recurrence of type II achondrogenesis in both sibs.     

Triply discordant triplets: probability, management options, and risks.

The spontaneous occurrence of triplets is rare. With increased utilization of "assisted reproductive technologies," multifetal gestations have become more common. The empiric fetal risk for major malformation is approximately 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is approximately 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation-stimulated triplet pregnancy complicated by 3-way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations.     

镜像综合征20例临床特征探讨

目的探讨镜像综合征病因、临床特征和妊娠结局。方法回顾性分析广州医学院第三附属医院2005年1月至2012年9月20例镜像综合征病例的临床表现。结果水肿胎儿发病率0．219％,镜像综合征发病率0．0472％。平均发病孕周27．95±3．72周,Bart’s水肿胎为镜像综合征的主要病因共12例,占60％,不明原因8例,占40％。超声和病理提示胎儿和胎盘水肿。母体100％发生水肿和蛋白尿,70％（14／20）发生高血压,20％（4／20）发生肺水肿。血液检查显示血液稀释HCT均值为27．58±2．72％,低血色素89．94±10．41g/L,低蛋白血症（白蛋白21．72±4．53g／L）,尿酸水平增高612．53±124．20umol／L,15％孕妇肝酶轻度增高。临床处理为对症及终止妊娠。分娩平均孕周31．28±2．65周,20例围产儿均死亡。阴道分娩12例,剖宫产8例。发生产后出血共7例,占35％（7／20）。母体症状在产后1—7天改善。结论镜像综合征病因主要为Bart’s水肿胎,表现为母体、胎儿、胎盘水肿三联征,围生儿预后不良,母体易发生高血压、肺水肿和产后出血,终止妊娠后,母体的情况得到迅速改善。     

Selective birth in twin pregnancy with discordancy for Down's syndrome

Amniocentesis is used for detection of genetic abnormalities. One difficult problem to resolve is the consequence of finding 1 abnormal and 1 normal fetus in cases of twin pregnancies. A review of the literature reveals 5 cases of 1 abnormal and 1 normal fetus in twin pregnancies. A most aggressive approach to this problem is selective termination of the abnormal fetus by intracardiac puncture and exsanguination. This report describes a case of twin pregnancy with discordancy for trisomy 21. Amniocentesis was performed on a 40-year-old nullipara who was 17 weeks pregnant. Advanced maternal age was the indication for the procedure. An ultrasound scan and chromosomal studies revealed twin fetuses, twin A with a normal karyotype (46, XY), and twin B with indicated trisomy 21 (46, XY + 21). After an extensive counseling session, the mother decided to undergo selective termination of the abnormal fetus. At 20 weeks' gestation, the procedure was carried out under real-time ultrasound guidance as described. At 40 weeks gestation, the patient delivered a 2980 g living male infant and a 120 g small, fibrosed, and infarcted fetus papyraceus (twin B). Both mother and surviving infant continue to do well. The risks of performing selective termination of abnormal fetuses, and technical considerations in this type of procedure are discussed.     

Triply discordant triplets: Probability,management options,and risks

The spontaneous occurrence of triplets is rare. With increased utilization of “assisted reproductive technologies,” multifetal gestations have become more common. The empiric fetal risk for major malformation is ～ 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is ～ 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation-stimulated triplet pregnancy complicated by 3-way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations. © Wiley-Liss, Inc.     

11～13+6孕周与14～17+6孕周胎儿超声筛查的对比

目的 评价非选择孕妇11～13+6孕周和14～17+6孕周胎儿超声筛查的作用.方法 2002年1月至2008年4月在中山大学附属第一医院行11～17+6孕周胎儿首次产前常规超声检查共3645例患者,其中11～13+6孕周组1556例,14～17+6孕周组2089例.比较两组胎儿结构异常的检出率及畸形类型构成比.结果 11～13+6孕周组和14～17+6孕周组胎儿结构异常首次检出率分别为2.3%(36/1556)和3.3%(68/2089),差异无统计学意义.两组胎儿结构异常类型构成比差异有统计学意义(P=0.03).11～13+6孕周组胎儿畸形前3位为颈部异常(项颈透明层增厚及颈部淋巴水囊瘤)占31.6%(18/57),胎儿水肿占15.8%(9/57),前腹壁异常占12.3%(7/57).14～17+6孕周组胎儿畸形前3位为心血管系统异常占16.7%(18/108),中枢神经系统异常占14.8%(16/108),前腹壁异常占12.0%(13/108).结论 11～13+6孕周胎儿超声检查能诊断多种致死性胎儿畸形及检测各种染色体异常超声标记;14～17+6孕周胎儿超声检查可观察相对细微的胎儿结构异常.11～13+6孕周是早期胎儿超声筛查的理想时间.     

Differentiation between eclampsia and cerebrovascular disorders by brain CT scan in pregnant patients with convulsive seizures

Six pregnant women with convulsions between 25 to 40 weeks of gestation were experienced. Among them, 4 patients were diagnosed as having intracranial hemorrhage and two as simple eclampsia. With the aid of brain CT scan, one case of arteriovenous malformation was detected and treated surgically with good prognosis for both the mother and the fetus. Two patients were diagnosed to have cerebral hemorrhage with subsequent penetration into the lateral ventricles and were treated conservatively. Their fetuses were delivered alive by cesarean section, but the mothers expired. The other patient with cerebral hemorrhage was treated surgically, and both the mother and the fetus survived. One of the simple eclampsia patients was noted to have a growth retarded fetus at 32 weeks of pregnancy with subsequent intra-uterine death, but the mother recovered after conservative treatment. Another patient at 40 weeks of pregnancy was also treated conservatively and both the fetus and the mother survived. Brain CT scan findings differed between these two eclampsia patients; local brain edema for the second patient and generalized brain edema for the first patient. Thus more active application of brain CT scan is recommended in managing pregnant patients with convulsions.     

超声多普勒检测晚孕期妊娠高血压综合征胎儿静脉导管血流的临床价值

目的探讨超声多普勒对晚孕期妊娠高血压综合征（PIH）胎儿静脉导管血流检测的临床价值。方法将临床确诊为PIH、孕周为32—40周的胎）L85例作为研究组,随机抽取相同孕周正常胎）LI32例为对照组。除外糖尿病、心脏病、胎儿畸形、多胎等影响因素。以超声多普勒检测胎儿静脉导管（DV）血流,分析每例胎儿的频谱波形变化,检测并计算相关的血流参数,并追踪每一例胎儿出生结局。结果研究组胎）LDV搏动指数（PI）、阻力指教（RI）、静脉前负荷指数（PLI）、S／a较对照组增高,两组比较有统计学意义。PIH胎儿不良出生结局组DV血流参数较正常出生结局组增高,两组比较有统计学意义。结论检测PIH胎儿DV血流参数可作为了解胎儿宫内情况及预测出生结局的有效指标,对指导围产期处理有重要临床价值。     

Prenatal diagnosis of thanatophoric dysplasia at 24 weeks

We report making the prenatal diagnosis of thanatophoric dysplasia at 24 weeks gestation. The ultrasound examination showed short limbs. By in utero radiological study, we could see the typical changes of this skeletal dysplasia. Radiological and histological studies confirmed the aborted fetus to be affected with thanatophoric dysplasia.     

Prenatal diagnosis of the prune belly syndrome

A male fetus with prune belly syndrome was diagnosed by ultrasound at 30 weeks of gestation. The diagnosis was confirmed after birth.     

Ultrasound diagnosis of cephalopagus conjoined twin pregnancy at 29 weeks

The authors report a case of a cephalopagus conjoined twin that was diagnosed at 29 weeks of gestation despite the mother having had two ultrasounds done previously. The fetus had one head and face, fused thoraces, common umbilicus but had two pelvises and two sets of genitalia. The fetus had four normally formed legs and arms.Antenatal ultrasound images are supplemented by post natal photographs. A review of literature, clues to ultrasound diagnosis and possible causes of missing this significant abnormality until the 3rd trimester are discussed.     

Prenatal diagnosis of Weyers syndrome (deficient ulnar and fibular rays with bilateral hydronephrosis)

A fetus with Weyers oligodactyly was studied after a previous sibling had been born with that condition. Prenatal diagnosis was undertaken using ultrasound to visualize the long bones, which were found to be severely affected by the condition at 19 weeks of gestation. Most notable were the ulnae and fibulae, which were very short; the fetus had bilateral hydronephrosis.     

Prenatal diagnosis of trisomy 1q21-qter: case report and review of literature

We report on a midtrimester fetus with multiple malformations, who was prenatally found to have pure partial trisomy 1q with duplication 1q21-qter. Prenatal ultrasound at 23 gestational weeks demonstrated craniofacial dysmorphism, ventriculomegaly, hand anomalies, and multiple visceral anomalies including cardiac defect, duodenal atresia, omphalocele, and urethral obstruction in the fetus. After pregnancy termination, external morphologic examination confirmed the sonographic characteristics, but autopsy was refused. Cytogenetic analysis (GTG banding) and subtelomeric probes (FISH) demonstrated an aberrant karyotype 46,XY,der(1)(1qter --> 1q21::1p36.3 --> 1qter) in a total of 139 amniotic fluid cells. Trisomy of the long arm of chromosome 1 is a rare condition. Large duplications of almost the entire 1q had so far been described in five mosaic cases. The present case and review of the literature suggest that duplication 1q21-qter is a serious condition with pre- or perinatal demise of all reported cases. This case further delineates the phenotype in trisomy 1q.     

Severe micrognathia, cleft palate, absent olfactory tract, and abnormal rib development: cerebro-costo-mandibular syndrome or a new syndrome?

We report on a family in which two sibs had apparently absent ribs and severe micrognathia on prenatal ultrasonography. The pregnancies were terminated at 19 and 12 weeks of gestation, respectively. Autopsy findings in the first fetus (19 weeks of gestation) included severe micrognathia, a U-shaped defect of the soft palate, marked postnuchal edema, absent olfactory bulbs, and cribriform plate and rib abnormalities. The ribs consisted of cartilage anteriorly, with only a small amount of fibrous tissue present laterally and posteriorly. The second fetus (12 weeks gestation) had agnathia, with a large U-shaped defect in the soft palate. There was moderate postnuchal edema. The ribs were unossified and there were gaps in the cartilage where primitive mesenchyme was present posteriorly and laterally. These findings are consistent with a severe form of cerebro-costo-mandibular syndrome. The early fetal histopathology of both cases suggests a possible mechanism by which the characteristic "rib gaps" of cerebro-costo-mandibular syndrome may develop, with evidence for abnormal function of a gene or genes involved in regulation of rib chondrogenesis.     

Properties of associations: Identity,nature, and clinical criteria,with a commentary on why CHARGE and Goldenhar are not associations

We report the use of fluorescent in situ hybridization (FISH) with a DNA library of chromosome 1-specific probes to confirm the karyotype, 46,XY,15, + der15,t(1;15)(q32.1; q26.3), obtained by prenatal periumbilical blood sampling from a fetus who exhibited multiple abnormalities by ultrasound examination. GTG-banding of chromosomes obtained from the mother showed a normal karyotype, while the father was unavailable for study. The propositus was born at 37 weeks gestation and survived for several weeks. Cytogenetic analysis performed after the birth of the male infant with multiple anomalies verified partial trisomy 1q. This patient is compared with other partial trisomy 1q patients reported in the literature. The usefulness of FISH is demonstrated in situations where fetal abnormalities are present with de novo chromosomal rearrangements where paternal chromosomes are unavailable for study. © 1994 Wiley-Liss, Inc.