Choroid plexus cysts: Is biochemical testing a valuable adjunct to targeted ultrasonography?

OBJECTIVE: We sought to determine whether biochemical testing is a valuable adjunct to ultrasonography in selecting patients with fetal choroid plexus cysts for amniocentesis. STUDY DESIGN: The study population consists of 128 patients who had fetal choroid plexus cysts detected during ultrasonography performed between 18 and 22 weeks' gestation. The patients had genetic counseling, and amniocentesis and biochemical testing were offered to all patients. The data were analyzed by dividing the patients into 3 groups. Group 1 had targeted ultrasonography only, group 2 had ultrasonography and maternal serum alpha-fetoprotein testing, and group 3 had ultrasonography and triple-screen (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and estriol) testing. Outcome was determined by fetal karyotype or by neonatal examination by a pediatrician for patients who declined amniocentesis. RESULTS: There were 25 patients in group 1. Isolated choroid plexus cysts were detected in 20 fetuses, and all had normal outcomes. Additional anomalies were detected in 5 fetuses. Two had normal karyotypes, and 3 had trisomy 18. There were 52 patients in group 2. The maternal serum alpha-fetoprotein levels were normal in 44 patients, 41 of whom had isolated fetal choroid plexus cysts. Of these 44 patients, 40 had normal outcomes, and 1 patient had a fetus with trisomy 18. The remaining 3 patients with normal maternal serum alpha-fetoprotein levels had additional fetal anomalies on ultrasonography, but the karyotypes were normal. The maternal serum alpha-fetoprotein levels were abnormal in 8 patients, of whom 6 had fetuses with isolated choroid plexus cysts and normal karyotypes. Two patients had additional fetal anomalies detected on ultrasonography and had abnormal karyotypes, 1 with trisomy 21 and 1 with trisomy 18. There were 51 patients in group 3. Results of the triple screen were normal in 32 patients. The choroid plexus cysts were isolated in 29 of the 32 patients, and all 29 fetuses had normal karyotypes. The other 3 patients with normal triple-screen results had additional fetal anomalies on ultrasonography. One fetus had normal chromosomes, and 2 had trisomy 18. The remaining 19 patients had abnormal triple-screen results. Among them, 16 fetuses had isolated choroid plexus cysts, 13 of whom were normal, 2 had trisomy 18, and 2 had a de novo unbalanced translocation. The remaining 3 fetuses had additional anomalies, and all 3 fetuses had trisomy 18. There were 14 fetuses with significant chromosomal abnormalities. Nine mothers were <35 years old, and 5 were >/=35 years old. CONCLUSIONS: This study shows the following: (1) The triple screen is a useful adjunct to targeted ultrasonography in selecting patients with fetal choroid plexus cysts for amniocentesis. (2) A normal triple-screen result and the absence of additional fetal anomalies on ultrasonography reliably exclude an underlying chromosomal abnormality, and amniocentesis is not indicated. (3) If the triple-screen result is abnormal, additional anomalies are seen on ultrasonography, or the mother is aged >/=35 years, then fetal karyotyping is recommended. (4) Patients who decline fetal karyotyping should have follow-up ultrasonography in 34 weeks' time.     

A prospective study of the incidence and significance of fetal choroid plexus cysts

Cysts of the choroid plexus of the lateral ventricle can be detected in the fetus during routine scanning at 16-18 weeks' gestation with an approximate incident of one in every 120 pregnancies. It is likely that in a high percentage of cases cysts are bilateral and that their recent discovery is mainly due to improvements in imaging technology. Although the great majority of cases resolve and do not result in any morbidity, five cases of trisomy 18 and one case of trisomy 21 associated with fetal choroid plexus cysts have been reported. In this prospective study, choroid plexus cysts were detected in 42 fetuses, resulting in 40 normal infants and 2 cases of trisomy 18. It is concluded that there may be a relationship between fetal choroid plexus cysts and trisomy 18. In order to obtain a more precise and accurate result, a multi-centre prospective study is being organized.     

Are choroid plexus cysts an indication for second-trimester amniocentesis?

Previous series that described fetuses with choroid plexus cysts have been too small to determine whether there is an association with trisomy 18 sufficiently high to warrant amniocentesis. To address this issue, we studied the incidence of choroid plexus cysts and other ultrasonographic abnormalities in 26 consecutive fetuses (13.5 to 36 weeks' gestation) with trisomy 18. Twenty of these 26 fetuses had major sonographic anomalies suggestive of aneuploidy. Seventeen of these 26 fetuses were 15 to 20 weeks and 5 of 17 (30%) had choroid plexus cysts. Six of our total 26 affected fetuses had no sonographic anomalies and therefore, on the basis of our data, 30% of these (1.8 fetuses) with trisomy 18 would have choroid plexus cysts without other findings. The incidence of choroid plexus cysts in all second-trimester fetuses (including normal fetuses and those with trisomy 18) is reportedly 1%. Given the known incidence of trisomy 18 (3/10,000), we calculated a total presumptive sample of 86,667 patients to yield our 26 fetuses with trisomy 18. Our hypothetical sample has 86,641 (86,667 - 26) fetuses without trisomy 18,858 of which would have choroid plexus cysts. Thus there would be one fetus with trisomy 18 for every 477 normal fetuses with choroid plexus cysts with no other defect seen. If amniocentesis were done to seek trisomy 18 in all second-trimester fetuses with choroid plexus cysts, two normal fetuses would be lost for every one with trisomy 18 identified.     

Choroid plexus cysts in the fetus: a benign anatomic variant or pathologic entity? Report of 41 cases and review of the literature

During a 22-month period, 6288 women undergoing prenatal sonographic studies in the second and third trimesters were evaluated prospectively to determine the incidence of choroid plexus cysts in the fetus, to follow the natural course of these cysts in intrauterine life, and to determine the association of chromosomal and anatomic anomalies in these fetuses. We diagnosed choroid plexus cysts in 41 fetuses, an incidence of 0.65%. Unilateral and bilateral cysts were equally frequent, and in most cases diagnosed by 21 weeks' gestation. On follow-up scans, the cysts had completely disappeared by 23-24 weeks in 80% of the cases, and by 28 weeks in another 10%. Once resolved, the cysts did not recur, and a normal sonogram in the late second trimester predicted normal scans in late pregnancy and in the neonate. One fetus had a chromosomal abnormality (trisomy 18). Associated anatomic anomalies were detected in three fetuses, including the one with trisomy 18. We believe that in the great majority of cases, fetal choroid plexus cysts are benign transient variants of normal intracranial anatomy. It is, however, important to conduct a careful sonographic search for associated anomalies. Chromosomal studies are strongly recommended whenever associated anatomic abnormalities are detected and when the choroid plexus cysts are large, bilateral, and persistent beyond 20-22 weeks' gestation.     

Choroid Plexus Cysts in the Fetal Brain

Summary: Choroid plexus cysts may be detected in the fetal choroid plexus on routine second trimester ultrasound scanning. The presence of these cysts is associated with trisomy 18 (Edward syndrome) in 3.47% of cases and with trisomy 21 (Down syndrome) in 0.46% of cases. The cysts themselves almost always disappear by 23 weeks and are thought to be a normal developmental variant. The world literature experience would indicate that the size of the choroid plexus cyst and the presence of bilateral cysts has no bearing on the magnitude of risk of chromosomal abnormality; 76% of babies with trisomy 18 also have other dysmorphic features which may be detectable by ultrasound. It is strongly advised that genetic counselling be undertaken and amniocentesis be considered when choroid plexus cysts are identified in the fetus .     

Quistes de plexos coroideos y riesgo de cromosomopatía

IntroductionSince they were first described in 1984, the presence of choroid plexus cysts during pregnancy have stimulated considerable debate concerning their possible relationship with chromosomal anomalies, mainly trisomy 18. Even today, the controversy persistsObjectiveTo identify which associated factors (cyst characteristics, associated anomalies and maternal age at diagnosis) should be considered to justify invasive karyotyping, bearing in mind that these techniques carry a risk of fetal lossMaterial and methodsWe analyzed data from one decade (January 1991-December 2000) corresponding to 26,500 fetuses who underwent ultrasound examination between weeks 14 and 22 of gestation. Choroid plexus cysts were considered as an ultrasound-negative formation of at least 3 mm in diameter located within the choroid plexusResultsChoroid plexus cysts were found in 366 fetuses (1.38%). Of these, eight fetuses presented chromosomal anomalies: six presented trisomy 18, one presented trisomy 21 and one showed chromosomal deletion at 6p. In all eight patients, choroid plexus cysts were bilateral and associated anomalies were detected. Mean maternal age was 36.5 yearsConclusionsWhen choroid plexus cysts are detected in the second trimester, detailed fetal investigation must be performed to find other possible markers of chromosomal anomalies even though some are difficult to detect ultrasonographically. Because the risk of fetal loss after amniocentesis is estimated at 1%, when other markers are absent, our results suggest that invasive karyotyping does not seem justified in pregnant women without additional risk factors     

More on management of choroid plexus cysts in the mid-trimester fetus

EDITORIAL COMMENT: We have published this pair of letters as a feature rather than in the correspondence column so it will not be lost to reference in the literature. Readers are also referred to a recently published review of the world literature concerning the risks of trisomies 18 and 21 in the second-trimester fetus with an isolated choroid plexus cyst (A). This study concluded that 'the likelihood of trisomy 18 was 13.8 times greater than the a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the second trimester. However, the likelihood of trisomy 21 was not significantly greater than the a priori risk with isolated choroid plexus cysts.' N.B.
(A) Yoder PR, Sabbagha RE, Gross SJ, Zelop CM. The second-trimester fetus with isolated choroid plexus cysts: A meta-analysis of risk of trisomies 18 and 21. Obstet Gynecol 1999; 93: 869–872
1. Choong S, Meagher S, Management of choroid plexus cysts in the mid-trimester fetus Aust NZ J Obstet Gynecol 1999; 39: 7–11
2. Goldstein H, Philip J. A cost-benefit analysis of prenatal diagnosis by amniocentesis in Denmark. Clinical Genetics 1990; 37: 24–263
3. Gupta J, Thornton J, Lilford R. Management of fetal choroid plexus cyst. Br J Obstet Gynaecol 1997; 104: 881–886.
4. Gratton R, Hogge W, Ashton C. Choroid plexus cysts and Trisomy 18: Risk modification based on maternal age and multiple-marker screening. Am J Obstet Gynecol 1996; 175: 1493–1497
Associate Professor Lachlan de Crespigny, Head of Ultrasound, Royal Women's Hospital, Carlton, Melbourne and Associate Professor Julian Savulescu Director, Ethics Unit, The Murdoch Institute, Royal Children's Hospital, Parkville, Melbourne and Dr Leslie J Sheffield, Director of Education and Training, Victorian Clinical Genetic Services, Royal Children's Hospital, Parkville, Melbourne.     

Disappearance of fetal choroid plexus cysts during the second trimester in cases of chromosomal abnormality

We report two cases in which isolated choroid plexus cysts (CPC) disappeared in the second trimester of pregnancy and were associated with chromosomal abnormahty (trisomy 21 and trisomy 18). In the trisomy 21 fetus the CPC was small (2.3 mm) and unilateral.     

The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of risk of trisomies 18 and 21

Objective: To assess the risk of trisomy 18 and trisomy 21 associated with isolated choroid plexus cysts diagnosed by ultrasound in the second trimester.Methods of Study Selection: We reviewed the unabridged PREMEDLINE and MEDLINE databases for articles written in the English language regarding second-trimester fetal isolated choroid plexus cysts and trisomies 18 and 21, published in the period 1987–1997. Selection criteria included only second-trimester, prospective studies in which the rate of fetal isolated choroid plexus cysts could be calculated, the number of fetuses with trisomy 18 and 21 was reported clearly, and pregnant women of all ages were included, rather than only those at high risk for aneuploidy due to advanced maternal age.Tabulation and Results: Thirteen prospective studies, comprising 246,545 second-trimester scans, were selected. Among 1346 fetuses with isolated choroid plexus cysts, seven had trisomy 18, and five had trisomy 21. For each study, a 2 × 2 table was constructed and the likelihood ratio of a positive test was computed. The likelihood ratios for trisomies 18 and 21 were found to be homogeneous (P = .08 for trisomy 18, and P = .16 for trisomy 21). The summary likelihood ratio and 95% confidence interval (CI) for each chromosomal abnormality were calculated using the Mantel-Haenszel fixed effects model of meta-analysis. The summary likelihood ratio for trisomy 18 was 13.8 (CI 7.72, 25.14, P < .001) and for trisomy 21 was 1.87 (CI 0.78, 4.46, P = .16).Conclusion: The likelihood of trisomy 18 was 13.8 times greater than the a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the second trimester. However, the likelihood of trisomy 21 was not significantly greater than the a priori risk with isolated choroid plexus cysts. The data supported offering pregnant women karyotyping to rule out trisomy 18 when maternal age at delivery is 36 years or older, or when the risk for trisomy 18 detected by serum multiple-marker screen is more than one in 3000.     

Choroid plexus cysts and trisomy 18: Risk modification based on maternal age and multiple-marker screening

Choroid plexus cysts are more common in fetuses with chromosomal aneuploidies, particularly trisomy 18. Although it is accepted that the risk of karyotypic abnormality justifies amniocentesis when associated abnormalities are present, disagreement continues as to the risk of trisomy 18 in a fetus with an isolated choroid plexus cyst. We propose consideration of maternal age and multiple-marker screening for chromosomal aneuploidy in the assessment of risk. Bayesian statistical modeling was used to calculate the risk of trisomy 18 from age-related risk figures for trisomy 18 and the incidence of isolated choroid plexus cysts in fetuses with trisomy 18. The risk was further modified on the basis of the ability of multiple-marker screening to detect fetuses with trisomy 18. From risk estimates calculated across maternal ages 20 to 45 years, the risk of trisomy 18 does not approach that of amniocentesis until a maternal age of ≥37 years. Therefore in the presence of an isolated choroid plexus cyst and normal multiple-marker screen results amniocentesis is justified only in the patient with advanced maternal age. (Am J Obstet Gynecol 1996;175:1493-7.)     

Second trimester choroid plexus cysts and trisomy 18

Objectives: In this study, the aims were to reveal the incidence of isolated choroid plexus cyst in our population, and to discuss the accuracy of distinguishing either an isolated or non-isolated choroid plexus cyst. Methods: The study population was consisted of 10 594 pregnant women. The patients with choroid plexus cysts were classified into two groups: isolated and non-isolated. Detailed ultrasonographic examination and genetic counseling were performed and triple screening test was ordered. The incidence, sensitivity, specificity, false-positive rate and likelihood ratio of cases with isolated choroid plexus cyst for trisomy 18 were determined. Results: Choroid plexus cysts were identified in 109 patients (109/10 594; 1.02%). In 102 patients isolated choroid plexus cysts, and in seven patients additional fetal anomalies supporting trisomy 18 were detected. Trisomy 18 was detected in four patients, and one of them had isolated choroid plexus cyst. The likelihood ratio in cases of isolated choroid plexus cysts for trisomy 18 was 9.51 (95% confidence interval, 0.2-41). Conclusions: According to the study the individual risk for trisomy 18 in isolated choroid plexus cyst should be calculated by using the likelihood ratio. These data allows the physician to express the individual risk of trisomy 18 and permits more accurate genetic counseling.     

Choroid plexus cysts-Association with trisomy: Prospective review of 16,059 patients

OBJECTIVE: The purpose of the study was to determine the incidence of isolated choroid plexus cysts in association with trisomy 18 and other abnormalities.STUDY DESIGN: All patients from June 1992 through December 1995 were followed up after a screening ultrasonography. Any patient with a choroid plexus cyst was offered genetic counseling and an amniocentesis. Screening ultrasonographic examinations were performed on 16,059 patients, and 301 patients had a fetus with a choroid plexus cyst. One hundred thirty patients elected to have an amniocentesis. Patients were followed up to delivery.RESULTS: Two hundred sixty-three patients had an isolated choroid plexus cyst. Thirty-eight patients had a choroid plexus cyst associated with additional risk factors. Risk factors included advanced maternal age, additional ultrasonographic abnormalities, past obstetric history, or family history. No abnormalities were noted in the group with an isolated choroid plexus cyst. Four patients had an abnormality when the choroid plexus cyst was associated with an additional risk factor, including two patients with trisomy 18 and one with trisomy 21.CONCLUSION: An isolated choroid plexus cyst was not associated with a trisomy or other abnormalities in this study. When a choroid plexus cyst was associated with an additional risk factor, 10.5% of the patients had an abnormality. Amniocentesis is recommended when a choroid plexus cyst is found in association with additional risk factors. (Am J Obstet Gynecol 1997;176:1381-3.)     

18-三体综合征胎儿超声声像特征分析

目的分析18-三体综合征胎儿超声声像特征,以期早期诊断与处理。方法回顾分析经染色体核型分析确诊的18-三体儿12例超声检查的资料。结果全部18-三体儿存在二个或以上异常超声声像表现。其中,胎儿生长受限、羊水过多表现率最高,各为58.3%;其次是心脏畸形,50.0%;再其次是脉络丛囊肿、单脐动脉、脑发育不全、上肢发育异常。在〈28周的胎儿中,超声异常的表现率最高的是心脏畸形、脉络丛囊肿,各为66.7%,其次是胎儿生长受限、羊水过多,各为50.0%。胎儿生长受限主要表现为股骨长度发育落后于正常。结论超声检查是产前筛查18-三体儿的有效手段。     

Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of the risk of trisomy 18

OBJECTIVE: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. STUDY DESIGN: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. RESULTS: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). CONCLUSION: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.     

Occurrence of fetal choroid plexus cysts in siblings: concerns regarding recurrence and chromosomal abnormality

Choroid plexus cysts (CPC) are a well-known ultrasound aneuploidy marker easily detectable at second-trimester ultrasound examination. However, their genetic etiology is totally unknown. We report two cases of Japanese mothers who carried two and three siblings respectively; all the fetuses that had CPC were noticed at second trimester. Genetic amniocentesis revealed that each fetus had different karyotypes, that is, trisomy 18 and 46,XX in the case of one mother, and trisomy 18, 46,XY and trisomy 21 in the case of the other. These observations indicate that the genetic basis of the cysts is not linked to abnormal chromosomes. We propose that careful ultrasound observation and genetic counseling of the siblings should be offered to patients who have previously had a baby with CPC, despite that baby having a normal karyotype.     

Cyst of the fetal choroid plexus: a normal variant?

Cysts of the choroid plexus have been identified ultrasonographically in second-trimester fetuses and usually have regressed by 24 weeks' gestation. Choroid plexus cysts have been linked with trisomy 18, and this possible association has prompted a review of our experience. Choroid plexus cysts were seen ultrasonographically in 38 consecutive fetuses between 15 and 28 weeks' gestation. Of these, 30 underwent repeat ultrasonograms after 24 weeks' gestation and showed complete resolution of the cysts. In 10 of the 38 fetuses, amniocentesis yielded normal karyotypes. A total of 36 patients were delivered of normal neonates at term. One patient was delivered of a normal neonate prematurely, at 34 weeks' gestation with a good outcome. Another fetus was delivered at 36 weeks' gestation because of late onset of nonimmune hydrops, which resolved without sequelae. No association between trisomy 18 and choroid plexus cysts was identified in this series.     

Choroid plexus cysts in fetuses with trisomy 18

An association between fetal choroid plexus cysts and trisomy 18 has been suggested. However, the prevalence of such cysts in aneuploid fetuses is unknown. To determine this frequency, we studied 14 fetuses with trisomy 18 examined at the Central Laboratory for Human Embryology. Five fetuses were found to have choroid plexus cysts on postmortem ultrasound examination. All those with cysts were earlier than 26 weeks in gestation, and the prevalence among second-trimester fetuses was 71.4%. In contrast, such cysts are reported in less than 1% of the general population of second-trimester fetuses. Thus, choroid plexus cysts are common in trisomy 18, and the finding of such cysts on a second-trimester ultrasound examination should suggest further evaluation, including chromosome analysis.     

Choroid plexus cysts in the 2d trimester--an indication for trisomy 18]

The application of high resolution ultrasound in the prenatal diagnosis enables a detailed differentation of the intracerebral structures in the fetus. In a period of 16 months (Jan. 1990-June 1991) we diagnosed at the "Center for prenatal diagnosis and therapy" at the Charité's Hospital in 14 fetuses among 1800 investigated plexus chorioideus cysts. A rapid karyotyping after cordocentesis was performed in 11 cases. In 3 of them a trisomy 18 could be detected. In one fetus having a normal karyotype we could find besides the cysts multiple structural anomalies. In these 4 cases the termination of pregnancy was performed. In the other 10 pregnancies we could observe a spontaneous regression of the plexus cysts. These results suggest that the prenatal diagnosis of plexus chorioideus cysts is a indication for cytogenetic evaluation in order to detect a trisomy 18.     

Cysts of the choroid plexus: personal experience]

Twenty-six cases of fetal choroid plexus cysts were diagnosed using ultrasonography at the Ultrasound Out-patients clinic of the University of Turin during the period 1989-1991. In 21 of these cases fetal karyotype was ascertained since, as has been reported in the literature, cysts of the choroid plexus may be associated with an anomalous karyotype (trisome 18 or 21). One of the 21 cases had an altered karyotype (trisome 21) (4.2%). The Authors stress the importance of a detailed ultrasound study of fetal morphology since, in the presence of structural anomalies, the incidence of trisome 18 is much higher. On the basis of these data, prenatal diagnosis in the event of the echographic presence of choroid plexus cysts appears to be valid since the risk of chromosome anomalies is much higher than in 35-year-old women.