Zoltán Bán

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.

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.

Dystrophin gene analysis in Hungarian Duchenne/Becker muscular dystrophy families - Detection of carrier status in symptomatic and asymptomatic female relatives

A comprehensive study of the Hungarian Duchenne/Becker muscular dystrophy (DMD/BMD) families is presented. Deletions in the hot spots regions were identified by multiplex PCR, whereas rare mutations were detected by Southern blot and multiplex ligation-dependent probe amplification (MLPA) techniques. DMD/BMD disease was confirmed and exact deletion borders were determined in 19 out of 135 affected males using multiplex PCR. Additional exons involved as well as rare exon deletions were identified by MLPA in 71 male patients, whereas duplications were observed in seven patients. In two DMD patients, the entire dystrophin gene and adjacent genes were deleted. Out of the 95 female relatives, 41 proved to be carriers, including three manifesting carrier females. Using MLPA method, a large portion of the Hungarian DMD/BMD patients and their female relatives were exactly genotyped. For the first time, the incidence and prevalence of asymptomatic and symptomatic female carriers in Hungary was estimated.

Incidence of chromosomal abnormalities in the presence of fetal subcutaneous oedema, such as nuchal oedema, cystic hygroma and non-immune hydrops

Introduction: The authors investigated the incidence of chromosomal abnormalities in subcutaneous oedema detected in the fetus by intrauterine ultrasonography. Material and Method: 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. Results: Intrauterine karyotyping in fetal subcutaneous oedema was carried out in 434 cases. The chromosomal investigation was made in nuchal oedema in 374 cases, in 120 patients the chromosomal examination was made in the first trimester because of nuchal translucency, and in 254 cases in the second trimester because of nuchal thickening. Cystic hygroma cases (27 patients), non-immune hydrops cases (20 patients), and combined cases of non-immune hydrops and cystic hygroma (13 patients) were investigated separately. In nuchal oedema, pathological karyotypes were detected in 8.33% in the first trimester and in 5.51% in the second trimester. Chromosomal abnormality was found in 48.15, 20, and 53.8% in cystic hygroma, non-immune hydrops, and combined occurrence of non-immune hydrops and cystic hygroma, respectively. Considering all of the changes accompanied by subcutaneous oedema, 50, 25 and 18.75% of the pathological karyotypes was X-monosomy, trisomy 18 and trisomy 21, respectively. Discussion: It was important to distinguish nuchal oedema and cystic hygroma, and in the case of non-immune hydrops, it was also important to discuss cases with or without cystic hygroma separately. During the investigations, cases of non-immune hydrops with or without cystic hygroma were evaluated as separate categories. Conclusions: The authors emphasize the differentiation of the various types of subcutaneous oedema and the importance of precise information about the risks, provided during genetic counselling.

Rare Case of Exomphalos Complicated with Umbilical Cord Teratoma in a Fetus with Trisomy 13

An exomphalos containing unusual solid and cystic mass was diagnosed during a routine ultrasound examination in the 17th week of gestation. Further investigations were planned but the pregnancy was terminated. The fetopathological examination revealed an umbilical cord teratoma. Although this entity is very rare it should be emphasized as a possible differential diagnosis when cystic lesion of the cord is detected. Large teratomas associated with abdominal wall defect may have poor fetal outcome and can be associated with structural and chromosomal abnormalities. In our case trisomy 13 was diagnosed.

Apolipoprotein E Allele Distribution in Trisomy 13, 18, and 21 Conceptuses in a Hungarian Population

Reports documented a higher frequency of apolipoprotein E (apoE) allele epsilon 4 among mothers of children diagnosed with Down syndrome. We studied the prevalence of apoE alleles among 56 conceptuses with trisomy 13, trisomy 18, or trisomy 21. The presence of the 3 most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism, and trisomy status was detected by fluorescent polymerase chain reaction followed by DNA fragment analysis and by conventional cytologic methods. We found no significant difference in the distribution of apoE alleles in the group of trisomy 21 fetuses compared with samples from healthy blood donors. The odds of having trisomy 18 for the apoE epsilon 4 group was 3-fold as high as for apoE epsilon 3 allele compared with the healthy control group. Furthermore, a statistically significant association was found for those with trisomy 18 and apoE epsilon 4, while for those with trisomy 13 and apoE epsilon 4, the test showed no significant association. The observed apoE allele epsilon 3 frequencies among patients with Down syndrome and healthy control subjects may help explain and support previous work that did not find high rates of atherosclerosis among these persons. The role of apoE alleles in the development of trisomies needs further study.

Prenatal Diagnosis, Phenotypic and Obstetric Characteristics of Holoprosencephaly

The diagnosis of fetal malformations, especially those of the central nervous system, is strikingly important in the practice of genetic counseling. Early diagnosis is very significant, not only because of the prognosis, but also because of the emotional effects caused by the accompanying craniofacial malformations. The summary of the obstetrical and diagnostical characteristics should be useful in the management of holoprosencephaly. The analysis of the 50 cases we encountered between 1981 and 2000, including the anatomical, diagnostic and clinical aspects, as well as the associated craniofacial malformations, forms the essence of our publication. In one of the examined cases a familiar recurrence was verified.

Recurrent trisomy 21 and uniparental disomy 21 in a family

Objective: A 32-year-old pregnant woman was referred to our genetic counselling because of recurrent trisomy 21 in the family. Analysis of amniotic fluid cell culture revealed karyotype 47,XY+21 of the fetus. Methods: Karyotyping and molecular analysis were undertaken in the fetal and parental samples to determine the origin of the extra chromosome 21. Results: Both parents had a normal blood karyotype. Microsatellite marker analysis showed maternal origin of the fetal extra chromosome 21. As the mother showed homozygosity for all investigated markers on chromosome 21, we also tested her family. We detected the same homozygosity in some family members which was consistent with isodisomy of the chromosome 21 caused by uniparental disomy (UPD). Conclusions: Here we report on a family in which multiple aneuploid conceptions occurred with trisomy 21, and molecular analysis showed that the euploidy of the investigated healthy family members is due to UPD21. This observation stresses the importance of prenatal cytogenetic and molecular analysis in case of parental UPD.

Noninvazív magzati Rh-meghatározás real-time PCR-módszerrel

INTRODUCTION In the last ten years the detection of fetal origin cells and cell free fetal DNA in maternal circulation opened new horizons in non-invasive prenatal diagnosis. The diagnostic possibilities are based on the differences between the maternal and fetal origin DNA. One of the differences could be the Rh blood group and the genetical background. The Rh incompatibility is the most frequent blood group incompatibilities in the clinical practice, which can cause fetal anemia, hydrops and even fetal death. AIMS The aim of this study was to detect the fetal DNA in maternal circulation, to determine the Rh status of the fetus, and to compare the reliability of the method with the data found in other studies. METHODS Blood samples and amnionic fluid samples were collected from 30 pregnant women, with Rh negative status, between 11-22 week of gestation presented for genetic amniocentesis at the 1st. Department of Obstetrics and Gynecology, Semmelweis University. After DNA isolation real-time PCR was performed in order to detect the exon 7 of the RhD gene located on the first chromosome (1p36.11.). RESULTS In 24 cases the PCR reaction gave same result in case of the DNA isolated from plasma and amniotic fluid, but in six cases there was no PCR product of plasma samples and the product was detectable in amniotic fluid samples. The exon 7 was detectable in 25 cases, and there was no product in 5 cases. CONCLUSIONS The real-time PCR method seems to be an easy and reliable method to determine the fetal Rh blood group. The sensitivity and specificity of the method in this study is in concordance with international data. The use of more than one probe could increase the sensitivity of the method.