Figure 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Source publication
It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes o...
Context in source publication
Context 1
... former description by Malone et al. (8) --an enlarged hypoechoic space at the back of the fetal neck, extending along the length of the fetal back, in which septations are clearly visible --was used as the definition of septated CH (Figure 1). Within the diagnosis, all patients were informed of an association between CH and fetal aneuploidy and were offered fetal karyotyping. ...
Similar publications
Background: Increased nuchal translucency (NT) is an important biomarker associated with increased risk of fetal structural anomalies. It is known to be contributed by a wide range of genetic etiologies from single-nucleotide variants to those affecting millions of base pairs. Currently, prenatal diagnosis is routinely performed by karyotyping and...
Background
Increased Nuchal Translucency (NT) is an important biomarker associated with increased risk of fetal structural anomalies. It is known to be contributed by a wide range of genetic etiologies from single nucleotide variants to those affecting millions of base-pairs. Currently, prenatal diagnosis is routinely performed by karyotyping and c...
Background:
The observed rate of termination of pregnancy (TOP) for Turner syndrome varies worldwide and even within countries. In this vignette study we quantified agreement among ten multidisciplinary prenatal diagnosis centers in Paris.
Methods:
We submitted online three cases of Turner syndrome (increased nuchal translucency, normal ultrasou...
Citations
... 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. ...
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.
... The first diagnostic suspicion of CH usually arises in the first trimester ultrasound, where a thickening of the nuchal fold ≥3mm (4) is observed; however, it has been considered that visualization in the cervico-occipital region of a cystic, bilateral and generally symmetrical area (septated or nonseptated) can also be considered to establish an ultrasound diagnosis (10). ...
... however, other studies have found no differences in terms of prognosis when evaluating these variables (10,12). ...
Introduction: Cystic hygroma (CH) is a rare congenital anomaly of the lymphatic system. It is characterized by cystic lesions predominantly in the fetal neck and its prenatal diagnosis has been associated with increased perinatal mortality, aneuploidy, and congenital malformations. Case presentation: Two cases of cervical cystic hygroma diagnosed during the second trimester of gestation are presented, one of them associated with bilateral clubfoot. Both fetuses underwent karyotyping by amniocentesis, which established that both were euploid (46 XY and 46 XX), as well as fetal nuclear magnetic resonance imaging that showed no associated major malformations. In the interdisciplinary follow-up performed 1 year after birth, no findings consistent with genetic syndromes or neurodevelopmental alterations were observed in either of the 2 cases. Conclusions: CH is a marker of poor fetal prognosis; however, euploid fetuses with this condition have a better prognosis if their lesion resolves, do not progress to hydrops fetalis, and do not present other associated malformations. Euploid fetuses with CH require specific genetic studies for RASopathies, such as Noonan syndrome, which were not available in the clinical approach of the 2 cases presented; however, typical postnatal characteristics of the disease were not evident in the clinical genetic evaluation.
... However, the prognosis of CH, which is affected by chromosomal abnormality and fetal malformation, [7][8][9][10][11] remains poor. [12][13][14][15][16] The identification of fetal CH increases the likelihood of termination of pregnancy by the patient. Many clinicians have recognized the MC importance of ultrasonic screening for genomic abnormalities in guiding healthcare for fetuses with CH during pregnancy. ...
... In terms of pregnancy outcome, the rate of full-term delivery of a fetus with CH fluctuates between 7.5% and 18.8%. [13,15,32] In this study, the full-term delivery rate of fetuses with CH was 30.8%, which was higher than that reported in the literature. The prognosis of isolated CH with a normal genome is generally good under normal birth conditions. ...
Background:
Cystic hygroma (CH) is a relatively common observation in prenatal ultrasounds; however, there are few studies about copy number variations (CNVs) of fetuses with CH.
Methods:
We performed a retrospective analysis on 40 pregnant patients (out of 8000 pregnant patients) whose fetuses had CH from November 2016 to June 2021. Villus, amniotic fluid, or umbilical cord blood samples were collected, based on the corresponding gestational age, for karyotype analysis and single-nucleotide polymorphism array (SNP-array).
Results:
Among the 40 fetuses with CH, 16 (40.0%, 16/40) exhibited isolated CH and 24 (60.0%, 24/40) exhibited CH combined with other ultrasound abnormalities. The most common CH-comorbid ultrasound abnormalities observed in this study were congenital heart disease (25.0%, 6/24), thickened nuchal translucency (20.8%, 5/24), and fetal edema (12.5%, 3/24). Karyotype and SNP-array analysis resulted in an overall detection rate of 30.0% (12/40). Karyotype analysis led to the detection of eight cases of pathogenic CNVs, among which 45, X was the most common. In addition to the above pathogenic CNV, four additional cases were detected by SNP-array. There was no significant difference in the observed pathogenic CNVs between isolated CH and CH combined with other ultrasound (31.3% vs 29.2%, P > .99). Karyotype analysis and SNP-array results influence whether parents terminate the pregnancy. When genetic abnormalities are detected in the fetus, the parents often choose to terminate the pregnancy.
Conclusions:
Our study emphasizes that genomic examination should be performed on fetuses with CH to confirm the etiology as soon as possible. During genetic counseling, all fetal characteristics should be carefully and comprehensively evaluated.
... In terms of pregnancy outcome, it has been reported that the rate of full-term delivery of fetus with CH uctuates from 7.5-18.8% [10,32,33]. In this paper, the full-term delivery rate of fetuses with CH was 30.8%, which was higher than that reported in literature. ...
Cystic hygroma (CH) is a somewhat common observation in prenatal ultrasounds; however, there is no consensus regarding the clinical management of fetuses with CH. A retrospective analysis was performed on 40 pregnant patients whose fetuses had CH from November 2016 to June 2021. Villus, amniotic fluid, or umbilical cord blood samples were collected according to the corresponding gestational age for karyotype analysis and single-nucleotide polymorphism array (SNP-array). Among the 40 fetuses with CH, 16 (40.0%, 16/40) exhibited isolated CH and 24 (60.0%, 24/40) exhibited CH combined with other ultrasound abnormalities. The most common CH-comorbid ultrasound abnormalities in this study were congenital heart disease (25.0%, 6/24), followed by thickened nuchal translucency (20.8%, 5/24), and fetal edema (12.5%, 3/24). After karyotype and SNP-array analysis, an overall detection rate of 30.0% (12/40) was achieved. Using karyotype analysis, eight cases of pathogenic copy number variations (CNVs) were detected, among which 45, X was the most common. In addition to the above pathogenic CNV, four additional cases of pathogenic CNVs were detected by SNP-array. There was no significant difference in pathogenic CNVs of isolated CH and CH combined with other ultrasound (31.3% vs. 29.2%, P = 1). Karyotype analysis and SNP-array results influence whether fetal parents terminate pregnancy. When genetic abnormalities are detected in the fetus, the parents often choose to terminate the pregnancy. Genomic examination should be performed on fetuses with CH to confirm the etiology as soon as possible. During genetic counseling, all fetal characteristics should be carefully and comprehensively evaluated.
... If they accept karyotype analyses, chorion villus sampling (CVS) or amniocentesis should be performed by a perinatologist. Previous studies have reported poorer perinatal outcomes in pregnancies with fetal cystic hygroma and associated aneuploidy (5,6). We carried out this retrospective study to evaluate the pregnancy outcomes of fetuses with cystic hygroma either with normal karyotype or with no karyotype analysis in the prenatal period. ...
... We think, our findings may be helpful to clinicians providing parental counseling for women who refuse karyotype analysis. Fetuses with cystic hygroma with normal karyotype and in whom no structural malformations are present pregnancy outcomes may be favorable as reported in the literature (5). The small number of cases with cystic hygroma and unknown karyotype in 21 cases are the main limitations of this study. ...
Objective:
To evaluate the obstetric outcomes of fetuses with cystic hygroma other than karyotype abnormalities and structural malformations.
Material and methods:
We conducted a retrospective study based on the review of medical records of pregnant women in whom ultrasonographic diagnosis of fetal cystic hygroma was established in the first trimester from January 2014 to October 2018. All patients were offered genetic counselling and prenatal invasive diagnostic procedures to obtain fetal karyotype. For ongoing pregnancies fetal echocardiography and detailed second trimester sonographic anomaly screening was performed by a perinatologist/pediatric cardiologist. Demographic characteristics of the women and results of the karyotype analysis were obtained from the database of our hospital and correlated with the obstetric outcome.
Results:
Within five-year period, there were 106 cases of fetal cystic hygroma. Of those, fetal cardiac malformations were detected in 4 and migrognathia in one. 85 women underwent fetal invasive procedures and in 52 of the cases, karyotype abnormalities were detected. Fetal outcomes of 33 cases with normal karyotype and 21 cases in whom karyotyping analysis were not performed due to patient refusal were enrolled into the study. Obstetric outcomes of 21 women who refused karyotyping consisted of 13 livebirths, 7 missed abortions and one fetal death, whereas those of 33 women with normal karyotype were; 12 livebirths, 12 missed abortions, 2 hydrops fetalis and 5 fetal deaths. 19 of 33 fetuses with normal karyotype and 8 of 21 fetuses in whom karyotyping were not performed were terminated.
Conclusion:
The presence of cystic hygroma carries a high risk for fetal karyotype abnormalities and cardiac malformations. Postnatal outcomes of the fetuses with cystic hygroma appeared to be correlated with the absence of structural malformations and karyotype abnormalities.
... A study by Sanhal et al. similarly found that fetuses with septated CH had poor perinatal outcomes. [11] In this study, 74% of all pregnancies were terminated due to either fetal abnormality or karyotype anomaly or both. Most of the fetuses (68%) presenting an aberrated chromosome were electively terminated by family consent. ...
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
... In many countries, including Romania, hypothyroidism is screened by TSH or T4 dosing by the dry spot on filter paper. For prophylaxis, the authorities have the obligation to supplement the iodine intake of the endemic inhabitants, by the iodization of the kitchen salt, of the marketed food [11][12][13][14][15]. ...
... In antenatal diagnosis, associated malformations should be screened for, to guide treatment options (Grade C). There are many reports of associations of LM with various other malformations or genetic abnormalities: notably, Noonan's syndrome [22,28] (level of evidence, 4), and trisomy 13, 18 and especially 21 [28,29] (level of evidence, 4). Organ abnormalities (essentially cardiac or urogenital), without necessarily being syndromic, are also frequently associated [22] (level of evidence, 4). ...
Objectives:
The authors present the guidelines of the French Society of Otorhinolaryngology (SFORL) for the diagnosis of cervical lymphatic malformation in adults and children.
Methods:
A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group, and finalized in a coordination meeting. Guidelines were graded A, B, C or expert opinion, by decreasing level of evidence.
Results:
The SFORL recommends that complete ENT examination should be performed to identify lesions at high risk of complication or associated with poor prognosis. In case of diagnostic doubt, especially in latero-cervical or oral floor lesions, fine-needle aspiration cytology should be performed before therapeutic decision-making. One or more validated classifications should be used to assess treatment efficacy and monitor progression. The reliability of antenatal diagnosis should be ensured by associating MRI to ultrasound. In antenatal diagnosis, the locoregional extension of the cervical lymphatic malformation should be evaluated accurately for prognosis, and associated malformations should be screened for, to guide treatment options.
... Malone et al. [14] suggested that compared with increased NT, first-trimester cystic hygroma has 5fold increased risk of aneuploidy [Odds ratio (95% confidence interval) ¼ 5.2 (2.9e9.6)]. In a study of 69 fetuses with septated cystic hygroma, Sanhal et al. [15] found that 40.6% (28/69) had aneuploidy including 14 cases (20.3%) of Turner syndrome. In a study of 2030 fetuses with first-trimester increased NT, Eckmann-Scholz et al. [16] found that 3.44% (70/2030) had aneuploidy including 25 cases of trisomy 21, 16 cases of trisomy 18, 6 cases of trisomy 13, 4 cases of Turner syndrome and 5 cases of others. ...
... In such cases, it is disputed whether the presence of septae alone can differentiate between increased NT and cystic hygroma (36). Other studies found that cystic hygroma is more likely to be associated with genetic anomalies than increased NT, although both conditions require genetic tests for diagnosis (37). ...
Background
The importance of fetal nuchal translucency was highlighted in the early 1990s as a useful first-trimester marker to identify fetal chromosomal abnormalities. Here, we report the prenatal diagnosis of a fetus with Niemann–Pick disease type C initially identified by first-trimester ultrasonographic markers and eventually confirmed by extensive genetic evaluation.
Case presentation
The fetus of a 30-year-old woman exhibited a cystic hygroma in the first trimester of pregnancy. The woman underwent chorionic villus sampling with extensive genetic investigations to identify the genetic cause of the ultrasonographic findings. Owing to normal karyotype results, further evaluation of 1,024 genes underlying structural abnormalities was performed. This test identified a homozygous mutation of the NPC2 gene (OMIM 601015), which has been reported to be pathogenic and responsible for Niemann–Pick disease type C2 (NPD-C2). Genetic evaluation of the parents found them to be carriers. Considering the poor prognosis, the parents decided to terminate the pregnancy. Ultrasonographic screening during the subsequent pregnancy showed normal findings; however, molecular testing for the previous familial mutation c.441 + 1G>A identified the fetus as homozygous for this mutation. Therefore, the parent chose to terminate the subsequent pregnancy as well.
Conclusion
We report the first prenatal diagnosis of NPD-C2 based on a cystic hygroma found during the first trimester of pregnancy as the sole indicator.
