Csaba Papp

Factors Influencing Parental Decision Making in Prenatal Diagnosis of Sex Chromosome Aneuploidy

OBJECTIVE: To evaluate factors influencing parental decisions toward continuing or terminating a pregnancy with prenatal diagnosis of sex chromosome aneuploidy. METHODS: We reviewed the records of patients with fetuses with sex chromosome aneuploidy between 1990 and 2001. A questionnaire survey of women who chose to terminate such pregnancies was designed to examine aspects of their decision-making process. RESULTS: Forty-nine of 89 pregnancies with sex chromosome aneuploidy were terminated (termination rate 0.55; 95% confidence interval 0.45–0.65). Pregnancies with abnormal ultrasound findings (14/16, 87%), with 45,X or 47,XXY karyotypes (26/36, 72%), and with nonmosaic karyotypes (30/48, 63%) were terminated significantly more often than pregnancies with normal ultrasound findings (35/73, 48%; P < .01), with 47,XXX or 47,XYY karyotypes (4/12, 33%; P < .05), and with mosaic karyotypes (5/25, 20%; P = .01). There was a trend (P = .136) toward a lower rate of termination from 67% to 36% across time, with a significant decrease from 67% to 7% in pregnancies with 47,XXX; 47,XYY; and mosaic karyotypes (P < .01), and no change in cases with 45,X and 47,XXY karyotypes (67% compared with 69%; P = 1.0). Abnormal sexual development and infertility were the greatest parental concerns related to termination. CONCLUSION: Fear of having a child with abnormal sexual development or infertility remains the major determinant of parental decision toward terminating pregnancy, resulting in consistently high termination rates across time in pregnancies with 45,X and 47,XXY karyotypes. In cases with 47,XXX; 47,XYY; and mosaic karyotypes, the declining termination rate across time is a consequence of recent studies reporting normal sexual development and fertility. LEVEL OF EVIDENCE: II-2

Prenatal diagnosis of Turner syndrome: report on 69 cases.

Objective. This study was conducted to evaluate the diagnostic value of different sonographic signs of fetuses with Turner syndrome in the first and second trimesters of pregnancy. Methods. Between 1990 and 2004, Turner syndrome was found in 69 of 22,150 fetal karyotypings. Congenital anomalies detected by sonography were analyzed. Results. Of the 514 (2.3%; 514/22,150) chromosome aberrations that were diagnosed, 69 Turner syndrome cases were found (13.4%; 69/514). Twenty‐four fetuses had a 45,X karyotype (34.8%), and 45 fetuses were mosaic (65.2%). Forty‐seven fetuses (68.1%; 47/69) showed symptoms on sonography. A substantial proportion of fetuses with Turner syndrome showed early‐onset signs that could be detected in the first trimester (29.8%;14/69). The most common findings with sonography were hygroma colli (26.1%; 18/69), fetal hydrops (11.6%; 8/69), cardiac defects (13%; 9/69), and increased nuchal translucency (13%; 9/69). Among heart defects, coarctation of the aorta was the most common (44.4% of all cardial defects). Soft markers were also detected with relatively high frequency (23.2%; 16/69). Conclusions. The diagnosis of severe Turner syndrome is possible in early pregnancy. A search for soft markers during second‐trimester sonography and extensive use of echocardiography may increase the detection rate of Turner syndrome.

Prenatal detection of trisomy 21 and 18 from amniotic fluid by quantitative fluorescent polymerase chain reaction.

Prenatal diagnosis of fetal trisomies is usually performed by cytogenetic analysis on amniotic fluid. This requires lengthy laboratory procedures and high costs, and is unsuitable for large scale screening of pregnant women. An alternative method, which is both rapid and inexpensive and suitable for diagnosing trisomies even from single fetal cells, is the fluorescent polymerase chain reaction using polymorphic small tandem repeats (STRs). In this paper we present the preliminary results of a larger study comparing parallel prenatal diagnoses of trisomies 21 and 18 using cytogenetics with quantitative fluorescent polymerase chain reaction using STR markers. The results obtained by the two techniques were concordant in all cases. This is the first study reporting significant numbers of prenatal diagnoses using the quantitative fluorescent polymerase chain reaction. We believe that further studies on greater numbers of samples will determine the absolute reliability of this technique. These results also provide a model for diagnosis of trisomy from single fetal cells isolated from maternal blood.

Genetic Amniocentesis in Multiple Pregnancy

Objectives: Second-trimester genetic amniocentesis is the most frequently used invasive prenatal diagnostic technique. Several reports have been published about the effect of genetic amniocentesis on fetal loss in multiple pregnancies over the past two decades. Here we analyze our experience with genetic amniocentesis in multiple pregnancies over the past 10 years. Methods: Details of 184 multiple pregnancies were processed in all cases in whom genetic amniocentesis was performed in women who presented at our department since 1990. The outcomes of 175 cases (95.1%) out of 184 genetic amniocenteses were available to us. As a control group, we followed up the outcome of 300 twin pregnancies in which no genetic amniocenteses were performed. Results: We found that the proportion of spontaneous losses in multiple pregnancies between the 18th and the 24th gestational weeks was 2.39%, whereas if genetic amniocentesis was performed the loss rate before the 24th week was 3.87%. The perinatal mortality rate was 10.03/1,000 in the group who underwent amniocentesis, while it was 10.52/1,000 in the group without amniocentesis. Conclusions: Our results suggest that the genetic amniocentesis performed in multiple pregnancies slightly increased (1.48%) the fetal loss rate until the 24th week. Beyond 5 weeks after the procedure, no consequent fetal loss should be expected. In our study the intervention did not have any undesired effect on perinatal mortality rates.

Prenatal Diagnosis of Trisomy 13 Analysis of 28 Cases

Objective. The purpose of this study was to investigate the role of second‐trimester sonographic examination in the prenatal diagnosis of trisomy 13. Methods. Of 22,150 fetal chromosome analyses, 28 fetuses with trisomy 13 were found between 1990 and 2004. Sonographic findings of this aneuploidy were analyzed in this study. Results. The average maternal age was 32.4 years; the average gestational age was 19.5 weeks. There was an 89.3% (n = 25) total prevalence of sonographic abnormalities in fetuses with trisomy 13 in this series. Major (structural) malformations were seen in 23 cases (82.1%), whereas minor anomalies were detected on sonography in 16 cases (57.1%). Although in 2 fetuses 1 minor anomaly was the only sonographic sign of trisomy 13, other cases with minor anomalies (87.5% [n = 14]) were multiplex malformations, in which combinations of major and minor anomalies were detected on sonography. The most frequently seen structural abnormalities were central nervous system and facial anomalies (64.3% [n = 18]). Among central nervous system anomalies, ventriculomegaly and holoprosencephaly were seen most frequently. Cardiovascular anomalies were detected in 53.6% (n = 15) of the fetuses with trisomy 13. This high frequency underlines the importance of echocardiography in diagnosing this aneuploidy. Among minor anomalies, increased nuchal translucency (21.4%) and echogenic bowel (17.9%) were the most common findings. Conclusions. Second‐trimester sonographic examination is capable of showing anomalies that are characteristic of trisomy 13; thus, the scan can indicate whether fetal karyotyping is advisable. Incorporation of careful assessment of the fetal cardiovascular system by sonography certainly increases the detection rate of trisomy 13.

Risk of Recurrence of Craniospinal Anomalies

The authors analyzed 1,655 situations from their Genetic Counseling Service over a 15 year period where the reason for counseling was craniospinal anomaly (neural tube defects and/or hydrocephalus) in the family. Excluding the obviously monogenically inherited cases, they investigated pregnancies undertaken after 1,285 isolated and 177 multiple forms of craniospinal abnormalities. The recurrence rate of craniospinal defects was found to be 3.66%, which is about ten times higher than the general population risk, supporting the theory of the multifactorial threshold model in the inheritance of these anomalies. The recurrence risks of neural tube defects and of hydrocephalus were 3.47% and 2.95%, respectively. The authors concluded that recurrence risk is mainly influenced by the pathoanatomic severity of the involved anomaly, the degree of relationship, and the number of affected relatives in the family. There is a positive correlation between the pathoanatomic severity of the anomaly in the proband and the offspring. At least in one-half of the cases the same type of anomaly was observed again in the offspring as in the proband. Attention is drawn to the fact that hydrocephalus (ventriculomegaly) is often manifested only in the second half of gestation. Therefore, performing ultrasound examination is strongly recommended not only at the 18th but at the 24th week of gestation, as well in pregnancies with a positive history of neural tube defects and/or hydrocephalus.

Chorionic Villus Sampling: A 15-Year Experience

The authors describe experiences gained over the period of 1984–1999 at two medical centers with chorionic villus sampling (CVS). Altogether 1,149 CVSs had been performed between the 10th and 32nd gestational weeks. Prior to 1993 the transcervical approach (TC-CVS), after 1994 the transabdominal method (TA-CVS) was used. Analysis of data collected within the framework of this study was based on the following factors: indications for sampling, complications and incidence of pregnancy loss. 91.6% of the CVSs were carried out for the purposes of cytogenetic examination of the fetus. Over the past few years an increasing number of procedures had been carried out for molecular-genetic tests (7.6% of the total number of cases). Though the primary indication for cytogenetic tests was the advanced age of the mother, a remarkable increase in the number of samplings had taken place for the purpose of examining ‘suspicious ultrasound findings’, minor anomalies detected by ultrasound. In this group the proportion of pathological cases was significantly higher (14%) than in all the other samplings, carried out for other indications. This data in itself underlines the importance of ultrasound screening performed in the 18–20th weeks of gestation. Over the first half of the period being reviewed (1984–1993, TC-CVS), a fetal loss of 4.8% occurring within 3 weeks from the date of sampling, dropped to 1.7% in the period subsequent to year 1994 (TA-CVS). In cases of TA-CSV, both the complications and spontaneous abortions were fewer. In 74.1% of the cases studied, birth had taken place after the 37th week of gestation. Premature births (6.4%) and stillbirth rate (1.1%) did not exceed normal rates observed in the general population. On the basis of our results, it is safe to say that in prenatal diagnosis, TA-CVS is a real alternative method of mid-trimester amniocentesis and it is recommended for use at any stage of the pregnancy.

Ivemark syndrome with asplenia in siblings

We describe two siblings with Ivemark syndrome. In both cases, absent spleen, symmetric liver, and lungs with three lobes were associated with complex cardiac malformation. The syndrome was diagnosed prenatally in the second case by fetal echocardiography at the twentieth week of pregnancy. The autosomal recessive mode of inheritance of Ivemark syndrome is further supported by these cases.

Calcification of the fetal heart - Four case reports and a literature review

Calcification of the heart and vessels in fetuses is a rare condition. It may be dystrophic or metastatic. An extremely rare form of vascular calcification has been termed ‘idiopathic arterial calcification of infancy’, which is inherited in an autosomal recessive pattern. We report four cases of myocardial calcifications of different origin diagnosed in utero. The correct diagnosis is very important in regard to genetic counselling. Copyright

Ultrasonographic Findings of Fetal Aneuploidies in the Second Trimester – Our Experiences

Objectives: The aim of this study was to determine the incidence of ultrasound findings in common fetal chromosomal defects on a relatively large series coming out from one institution. We also tried to evaluate possible clusters of ultrasound signs of major chromosomal defects. Methods: Of the 22,150 fetal karyotypings, 514 abnormal karyotypes (2.3%) were diagnosed prenatally between 1990 and 2004. Of them, 374 were further evaluated for abnormal ultrasound signs in this study. These represented the major chromosomal defects of Down syndrome (n = 207), trisomy 18 (n = 70), trisomy 13 (n = 28) and Turner syndrome (n = 69). Results: The incidences of major structural defects and minor anomalies were evaluated then sonographic signs with the highest incidences were established in each of the major chromosomal defects. In fetuses with trisomy 13, besides cardiac defects, the most frequently seen structural abnormalities were central nervous system anomalies and facial anomalies. In fetuses with trisomy 18 and trisomy 21, cardiac anomalies were the most common structural sonographic features, whereas the most common findings were hygroma colli and fetal hydrops in fetuses with Turner syndrome. As far as minor anomalies are concerned, increased nuchal fold was the most predictive marker of each major aneuploidy. Choroid plexus cysts were more common in trisomy 18, whereas echogenic intracardiac foci were more frequently detected in fetuses with trisomy 13 and trisomy 21. Conclusion: This study may help to select the most predictive components of the genetic sonogram which may assist the counseling of women for the actual risk of the major chromosomal abnormalities.