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The authors investigated the incidence of chromosomal abnormalities in subcutaneous oedema detected in the fetus by intrauterine ultrasonography.
In the 10-year period, intrauterine karyotyping was performed in pregnancies with positive ultrasound findings for subcutaneous oedema, such as nuchal oedema, cystic hygroma and non-immune hydrops.
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Edwards' syndrome, also known as trisomy 18, is a genetic disease caused by an extra copy of chromosome 18 in some or in all of the body cells [1, 2]. It is the second most common autosomal trisomy after trisomy 21(with an incidence of 1 in 8000 births) [3] but it is also more serious. Almost half of trisomy 18 infants die within the first week of...
Introduction:
The aim of this study is to describe the performance of first trimester screening (FTS) for trisomy 21 using maternal age, serum biochemistry and fetal nuchal translucency (NT) in a single center and to evaluate the effect of nasal bone on screening performance.
Material and methods:
In 12,585 singleton pregnancies, the NT and nasa...
Trisomy 18 (T18) remains the second most common aneuploidy. It is associated with multiple congenital anomalies and causes intrauterine fetal demise in the most severe cases.
To examine the screening performance of ultrasound-based protocols for detecting T18, we aimed to determine the most common signs and their prevalence in fetuses with T18 to d...
This study assesses the performance of noninvasive prenatal testing (NIPT) for fetal aneuploidies in a mixed risk factors pregnancy population.
Data review of 169 pregnant women undergoing prenatal aneuploidy screening in a single tertiary medical center was conducted. Indications included maternal anxiety, advanced maternal age, abnormal nuchal tr...
Citations
... The chromosomal abnormality most frequently associated with cystic hygroma is monosomy X or Turner syndrome (45,X) [5] . Note also Trisomy 21, 18 and 13, as well as Klinefelter syndrome (47, XXY) [6] . Furthermore, intrauterine exposure to alcohol has also been associated with the development of cystic hygroma. ...
Hydrops fetalis refers to the excessive accumulation of fluid in the extracellular compartment of the fetus. Cystic hygroma is a congenital malformation of the cervical lymphatic system responsible for an accumulation of lymphatic fluid commonly in the retrocervical region. Cystic hygromas are most often associated with chromosomal abnormalities. When a cystic hygroma is diagnosed in utero, the fetal survival rate is only 2-6%. When hydrops fetalis is present with cystic hygroma, the mortality rate is close to 100%. We present here the case of a 23-year-old primigravida in whom an ultrasound performed at 17 weeks of amenorrhea revealed a posterior cervical cystic hygroma associated with hydrops fetalis, the evolution of which was marked by intrauterine fetal death two weeks later. Keywords: Hydrops fetalis, Cystic hygroma, Chromosomal abnormalities, Prenatal diagnosis.
... Twentynine papers were secondarily excluded from data analysis: 12 papers for inadequate selection criteria to invasive genetic testing [19][20][21][22][23][24][25][26][27][28][29][30]; in 5 papers, the indication to genetic testing was inadequate for incremental yield [31][32][33][34][35]; in 4 papers, it was not possible to distinguish multiple gestations [36][37][38][39]; 3 papers did not provide appropriate differentiation between hygroma and iNT [2,40,41]; 3 papers included data from postnatal, live births and postmortem examination [42][43][44]; 2 papers provided a partial report of data about fetuses' malformations [45,46]. A total of 59 papers were adequate for quantitative analysis: 43 papers described the diagnostic application of karyotype, CMA, Rasopathy testing and/or ES in iNT cases (Table 1) [14,; 14 papers described their application in cystic hygroma (Table 2) [11,12,[89][90][91][92][93][94][95][96][97][98][99][100], and 2 papers their application in both iNT and cystic hygroma (Tables 1 and 2) [101,102]. Data concerning postnatal outcomes were retrieved from 17 papers for iNT ( The table illustrates data retrieved from the reference papers on the diagnostic yield of karyotype and the progressively incremental diagnostic yield of CMA in karyotypenegative cases, of RASopathy testing in karyotype-and CMA-negative cases, and ultimately of ES with iNT. For each reference, the cases were divided in categories based on the dimension of the NT and on whether the association with major fetal anomalies was reported or not. ...
Fetal Nuchal fluid collections can manifest with two distinct presentations attributable to the same phenotypic spectrum: increased nuchal translucency (iNT) and cystic hygroma. The prenatal detection of these findings should prompt an accurate assessment through genetic counseling and testing, including karyotype, chromosomal microarray analysis (CMA) and multigene RASopathy panel. We performed a systematic review of the literature and meta-analysis, to calculate diagnostic yields of genetic testing in fetuses with iNT and cystic hygroma. We compared the results with a cohort of 96 fetuses with these isolated findings. Fetuses with isolated NT ≥ 2.5 mm showed karyotype anomalies in 22.76% of cases and CMA presented an incremental detection rate of 2.35%. Fetuses with isolated NT ≥ 3 mm presented aneuploidies in 14.36% of cases and CMA had an incremental detection rate of 3.89%. When the isolated NT measured at least 3.5 mm the diagnostic yield of karyotyping was 34.35%, the incremental CMA detection rate was 4.1%, the incremental diagnostic rate of the RASopathy panel was 1.44% and it was 2.44% for exome sequencing. Interestingly, CMA presents a considerable diagnostic yield in the group of fetuses with NT ≥ 3.5 mm. Similarly, exome sequencing appears to show promising results and could be considered after a negative CMA result.
... DovePress finding was noted at transabdominal mid-trimester scanning and was found strongly associated with monosomy X (45,X, Turner syndrome) and other aneuploidies. [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] A study of 15 fetuses with cystic hygroma appearing as single or multiloculated fluid-filled cavities noted that none of the fetuses survived. Eleven of the fetuses (73%) had karyotypes consistent with Turner's syndrome. ...
First-trimester septated cystic hygroma occurs in approximately 1 in 268 pregnancies and has long been associated with a markedly increased risk of fetal aneuploidy and, among euploid fetuses, an increased risk of structural anomalies primarily affecting the cardiac and skeletal systems. Invasive prenatal diagnosis – chorionic villus sampling and/or amniocentesis – encompasses the time-honored clinical tools for the next step in management following prenatal sonographic diagnosis of first-trimester septated cystic hygroma. Currently, prenatal cell-free DNA (cfDNA) screening for fetal aneuploidy with select microdeletions is gradually replacing the considerably less sensitive, and labor-intensive combined first-trimester screening. These new technologies have opened potential new venues in the clinical management of this ominous late first-trimester sonographic diagnosis. Advances in cfDNA technologies are now permitting detection of chromosomal copy number variants (CNV) larger than 7Mb across genome and select serious single-gene disorders (mainly impacting skeletal and neurological development), affecting quality of life and may benefit from medical and/or surgical management. This commentary will address the available non-invasive prenatal screening technologies, which clearly enhance immediate genetic analysis modalities applicable in the presence of the complex sonographic finding of first-trimester septated cystic hygroma.
... In this strictly defined NIHF cohort study, the percentage of NIHF with confirmed etiology was similar to Sparks's (48% vs. 44%) [7] but was smaller than other published series. Previous studies included all fetal structural anomalies that might cause NIHF, such as congenital cardiac defects or multiple structural abnormalities that might be the prenatal phenotype of genetic disorders, and categorized them as confirmed etiologies associated with NIHF [8,[17][18][19]. In theory, the proportion of confirmed cases should be higher than Sparks's, as 66% of cases performed ES in the present study. ...
(1) Background: Numerous etiologies may lead to non-immune hydrops fetalis (NIHF). However, the causes remain unclear in half of NIHF cases following current standard assessment. The application of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) can improve the identification of the etiologies. This study aimed to investigate the etiologies of NIHF in the era of next-generation sequence (NGS) following a unified prenatal work-up flow for diagnosis. (2) Methods: A retrospective analysis was conducted on NIHF cases that were collected prospectively to explore the underlying etiologies according to a unified prenatal diagnosis work-up flow at Shanghai First Maternity and Infant Hospital between Jan 2016 and Dec 2019. The medical records for all NIHF cases were reviewed, and the causes of NIHF were classified as confirmed (diagnostic), suspected, or unknown. (3) Results: Prenatal and postnatal medical records for a total of 145 NIHF cases were reviewed, 48.3% (70/145) of the cases were identified to be with confirmed etiologies, and 10.3% (15/145) with suspected etiologies. Among 85 cases with confirmed or suspected etiologies, 44.7% were diagnosed with genetic disorders, 20% with chylothorax/chyloascites diagnosed postnatally, 12.9% with fetal structural anomalies, 12.9% with fetal anemia, 7% (6 cases) with fetal arrhythmia, and 2.3% (2 cases) with placenta chorioangioma. In cases with genetic disorders, 8 aneuploidies were detected by CMA, and 30 cases had single-gene disorders identified by ES (29/30) or targeted gene panel (1/30). There were still 41.4% cases (60/145) with unknown causes after this unified prenatal diagnostic work-up flow. (4) Conclusions: In the era of NGS, the causes of NIHF were identified in 58.6% of cases, with genetic disorders being the most common ones. NGS is helpful in determining the genetic etiology of NIHF when CMA results cannot explain NIHF, but 41.4% of cases were still with unknown causes under the unified prenatal diagnostic work-up flow in this single-center study.
... Studies including different regions of Turkey, declared this rate between 4,7-13%(9-12). The higher rate detected in this study might be a result of high percentage of non-immune hydrops fetalis that has 20% risk of fetal chromosomal anomaly (14,15). This study showed that 11.6% of patients had chromosomal anomaly. ...
... Ultrasonographic diagnosis of CH is usually obtained in the first trimester and the lesion can appear in septated or nonseptated forms. [13] More than 80% of pregnancies affected by CH will result in an abnormal outcome, including chromosomal abnormalities, genetic syndromes, structural anomalies, spontaneous abortion, fetal loss, or neonatal death. [8] Most cases of chromosome anomalies are aneuploidies such as Turner syndrome, Down syndrome, Klinefelter syndrome, and trisomy 18 and 13. [13] Similar to the literature data, this study shows a high rate of aneuploidy among fetuses with CH. ...
... [13] More than 80% of pregnancies affected by CH will result in an abnormal outcome, including chromosomal abnormalities, genetic syndromes, structural anomalies, spontaneous abortion, fetal loss, or neonatal death. [8] Most cases of chromosome anomalies are aneuploidies such as Turner syndrome, Down syndrome, Klinefelter syndrome, and trisomy 18 and 13. [13] Similar to the literature data, this study shows a high rate of aneuploidy among fetuses with CH. The incidence of abnormal karyotype in our series (58%) is relatively higher than many previous reports [8,9,14] but similar to some others. ...
Objective:
Genetic burden, fetal malformations, and fetal outcomes of 93 fetuses with cystic hygroma (CH) are
reported from a single center in Turkey.
Patients and Methods:
Pregnancies, having a diagnosis of fetal CH, detected between January 2010 and October 2016,
were included in the study except fetuses having increased nuchal translucency. Fetal age/gender, maternal age, the age of pregnancy, types of fetal malformations, karyotype, and outcomes were evaluated.
Results:
The average gestational age was 16.2weeks. Nearly 47% of
the pregnancies had multiple congenital anomalies, of which 58% had a chromosomal anomaly. Chromosomal anomaly rate was 68.2% in patients with hydrops fetalis. Aneuploidies were major chromosomal defects. All trisomies were of regular type except one with Robertsonian translocation
(46, XY, +13, rob[13;14][q10;q10]). Seventy four percentage pregnancies were terminated due to either fetal/karyotype anomaly.
Conclusion:
Characteristics of fetal CH were similar in different ethnical backgrounds. Aneuploidy is the dominant chromosomal constitution of fetal CH. Little information was known about the genes involved. Gene dosage effect implies that fetal CH is a complex genetic situation
involving multiple genes interactions. For proper genetic counseling, each fetus with CH should be karyotyped, and fetal ultrasound examination should be performed. In the case of normal chromosome set, application of aCGH should be considered.
Keywords:
Fetal cystic hygroma, genes, karyotype, outcome
... p97.5 th when FTCS risk is low and it suppose a small increase in cost because there are 21 pregnant women that meet these criteria (Group A, Table 5). An increased NT (p99 th or !3.5 mm) is associated with a high risk of chromosomal abnormalities [11], being monosomy X, T21 and T18 cases the more frequent unbalanced karyotypes found in these cases [14,17,18]. NT in p99 th is an indication for invasive test but we think that it is necessary to get the result of FTCS in these pregnancies because it provides information that can help women to make a decision about all their options, mainly when the NT is <3.5 mm. ...
Objective:
To assess the results of the first trimester combined test to design a prenatal protocol for the introduction of the cell-free fetal DNA test as a contingent screening model.
Method:
An observational retrospective study in 12,327 singleton pregnancies to analyze the results of the combined first trimester screening, the nuchal translucency ≥97.5 percentile, their cytogenetic results and birth outcomes.
Results:
A total of 533 (4.3%) pregnant women had a risk in combined first trimester screening above 1/300. In this group, sixty nine had an unbalanced karyotype. The abnormal/normal karyotype ratio was 1/28 in pregnant women with intermediate risk (1/51-1/300) for trisomy 21 and trisomy 18, 1/58 with intermediate risk just for trisomy 21 and 1/37 with intermediate risk just for trisomy 18. A 19.8% of the unbalanced karyotypes had chromosomal abnormalities other than trisomies 21, 18 and 13. Two false negatives cases at first trimester combined screening presented a nuchal translucency ≥ p97.5th.
Conclusion:
We propose the introduction of the cell-free fetal DNA test when the risk of first trimester combined screening is intermediate (1/51-1/300) and when nuchal translucency is ≥ p97.5th with a low risk in the combined screening. This policy would allow us to continue to detect uncommon chromosomal abnormalities.
... [11] Studies in CH patients have found karyotype anomalies to be approximately 50%-55%. [12,13] Turner syndrome and Down syndrome have been found to be the most common karyotype abnormalities in different case series in CH cases. [13,14] In this large-scale case study, aneuploidy was detected in 54% of 729 cases and major congenital anomaly was observed in 28% of patients with normal karyotypes. ...
... [19] In the studies performed, intrauterine karyotype analysis is recommended in the presence of subcutaneous edema in USG such as nuchal edema, CH, or non-immune hydrops. [4,12] Because of the CH patients at risk for bad obstetric history invasive prenatal diagnostic tests for use in these patients is recommended. There are studies advocating that karyotype analysis should be performed with methods such as amniocentesis and CVS in cases where CH is detected. ...
... In studies showing an increase in aneuploidy with an increase in NT thickness, aneuploidy risk was found to be 48% inthose with NT thickness between 3 and 5 mm and 60% in the fetuses with NT thickness >5 mm. [12,21] In another study conducted in this regard, it was determined that every 1-mm increase in NT thickness increased the abnormal karyotype ratio by 44% and the major congenital anomaly rate by 26%. [15] In our study, the aneuploidy risk was 36.1% in patients with NT thickness between 3 and 5 mm, and the aneuploidy risk was 56% in patients with NT thickness >5 mm. ...
... CH may be a part of generalized lymphatic dysplasia, or it may cause cardiac dysfunction due to decreased preload, leading to an end result of nonimmune hydrops fetalis (9). When there is no fetal structural anomaly, genetic syndrome, or abnormal karyotype, the CH is not complicated by hydrops and generally regresses with a better prognosis (10). ...
p>We herein describe a woman with two consecutive pregnancies affected by fetal nuchal cystic hygroma (CH) with a normal karyotype.
A 33-year-old woman (gravidity 2, parity 1) was referred to us because of fetal hydrops. No consanguinity or Rh isoimmunization was involved in her current or previous pregnancy. First-trimester ultrasonography revealed nuchal CH, and chorion villus sampling was performed to exclude aneuploidy.
In the first pregnancy, the CH had regressed and aortic coarctation was detected by second-trimester fetal echocardiography. In the current pregnancy, the CH had progressed and was complicated by the development of nonimmune hydrops. Termination of the pregnancy was performed at 21 weeks’ gestation.
Recurrence of fetal CH in subsequent pregnancies is extremely rare. CH with a normal karyotype can be inherited as an autosomal recessive trait. This report describes a woman with recurrent CH with normal karyotypes and different prognoses</p
... There are numerous studies of the incidence of chromosomal abnormalities in the presence of major fetal anomalies or various ultrasonographic soft markers in the literature. Over the limit value of nuchal translucency (NT), pathological chromosomal sets have been reported in more than 20% of cases [5][6][7][8][9]. According to previous studies, the chromosome abnormality rate varies from 3.4% to 39% when nuchal fold thickness is present [10,11]. ...
... Considering that the chromosomal abnormality rate was 36.8% in the CH group, the authors conclude that association with NIH results in a twofold increase in the rate of abnormal karyotype. Supporting the present findings, Beke et al. discovered chromosomal abnormalities in 20% of CH cases, while the chromosomal abnormality rate was 53.8% in cases of CH with NIH [7]. In a similar study by Nadel et al., chromosomal abnormalities were identified in 46.5% of CH cases, while CH and NIH occurring together was associated with pathological karyotypes in 83.78% [13]. ...
... Many researchers agree that monosomy X is the most common type and trisomy 21 is the second most common in this group; however, Beke et al. reported higher rates of trisomy 18 (38.46%) than monosomy X (15.38%) in their study [7]. ...
Purpose:
Subcutaneous edema detected sonographically in the forms of nuchal edema, cystic hygroma (CH), or non-immune hydrops (NIH) may be a sign of chromosomal abnormalities. The aim of this study was to investigate the chromosome abnormality incidence in fetuses with nuchal edema, CH, or NIH.
Materials and methods:
The authors performed cytogenetic analysis of 218 singleton fetuses with ultrasound diagnosis of subcutaneous edema in the forms of nuchal edema in the first and second trimesters.
Results:
Chromosomal abnormality rates were 30.4, 10.4, 36.8, 34.1, and 60% in the nuchal translucency (NT), nuchal fold thickness (NF), CH, NIH, and CH with NIH groups, respectively. In 71 cases with detected chromosomal abnormalities, 37%, 44%, 15%, and 4% of the pathologic karyotypes were identified as monosomy X, trisomy 21, trisomy 18, and trisomy 13, respectively.
Conclusions:
This study confirms that subcutaneous edema detected sonographically, in the forms of nuchal edema, CH, or NIH, is a significant indicator of abnormal karyotype and deserves further investigation.
