Search

Purpose:  To determine the true- and false-positive rates of cf-DNA testing in a cohort of patients from tertiary care centers and assess the impact of ultrasound examinations in pregnancy management., Materials and Methods:  Clinical, cytogenetic and ultrasound data of 101 consecutive fetuses were collected retrospectively. Cases were classified into five groups according to the ultrasound findings. Karyotyping, interphase FISH and microarray techniques were used for follow-up studies., Results:  The overall false-positive rate was low for trisomy 21 (T21, 8.2 %), but significantly higher for trisomy 18 (T18, 40 %), monosomy X (MX, 50 %), X/Y trisomies (57.1 %), trisomy 13 (T13, 71.4 %). While single cases of trisomy 16, trisomy 22 and 8q duplication positive in cf-DNA were confirmed, 3 microdeletions (1p36 and two 22q11.2) were not. About 75 % of confirmed T21's and all confirmed T18 and T13 had major markers and/or malformations. While false-negative cases (two T21, one T18 and one T13) were identified due to abnormal ultrasound findings, all false-positive cases were normal sonographically. Ultrasound findings of confirmed trisomy 16, 22, dup8q, monosomy X and other X/Y aneuploidies were unspecific. Term placenta studies were helpful to assess the role of confined mosaicism in unconfirmed cf-DNA test results. A vanishing twin has been observed as the likely cause of one false-positive T18., Conclusion:  Our study contributes clinical data on discrepant cf-DNA testing results, corroborates the need for confirmational invasive testing and underscores the benefit of expert ultrasound in the prevention of fatal diagnostic errors., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Partial deletion of the long arm of the chromosome 13 is a rare chromosomal aberration and may present with microcephaly, colobomata, microphthalmia, distal limb and digital anomalies, cardiac defects, brain and urogenital malformations, anal atresia and growth restriction., Case: We report such a case in 25th week of gestation referred for sonographic examination which revealed growth restriction, microcephaly, Dandy-Walker malformation, right microphthalmia, micrognathia, marked nuchal edema, four fingers-oligodactyly in feet and in hands with thumb aplasia and ambiguous genitalia. Chromosome analysis identified chromosome 13q deletion [46 XY del (13) (13q31.2/q32.1 --> qter)]. Postmortem examination confirmed prenatal findings and showed aniridia, low-set ears, cryptorchidism, and anal atresia., Conclusion: Detection of Dandy-Walker malformation, microphthalmia, oligodactyly with thumb aplasia and growth restriction during prenatal ultrasonography should be a reminder of deletion of chromosome 13q and warrant cytogenetic analysis.

Childhood-onset spinal muscular atrophy (SMA) is one of the most common neurodegenerative genetic disorders. SMN1 is the SMA-determining gene deleted or mutated in the majority of SMA cases. There is no effective cure or treatment for this disease yet. Thus, the availability of prenatal testing is important. Here we report prenatal prediction for 68 fetuses in 63 Turkish SMA families using direct deletion analysis of the SMN1 gene by restriction digestion. The genotype of the index case was known in 40 families (Group A) but unknown in the remaining 23 families (Group B). A total of ten fetuses were predicted to be affected. Eight of these fetuses were derived from Group A and two of these fetuses were from Group B families. Two fetuses from the same family in Group A had the SMNhyb1 gene in addition to homozygous deletion of the NAIP gene. One fetus from Group A was homozygously deleted for only exon 8 of the SMN2 gene, and further analysis showed the presence of both the SMN1 and SMNhyb1 genes but not the SMN2 gene. In addition, one carrier with a homozygous deletion of only exon 8 of the SMN1 gene was detected to have a SMNhyb2 gene, which was also found in the fetus. To our knowledge, these are the first prenatal cases with SMNhyb genes. Follow-up studies demonstrated that the prenatal predictions and the phenotype of the fetuses correlated well in 33 type I pregnancies demonstrating that a careful molecular analysis of the SMN genes is very useful in predicting the phenotype of the fetus in families at risk for SMA., (Copyright 2002 John Wiley & Sons, Ltd.)

The parental origin of the additional chromosome complement in a total of 17 cases of triploidy was determined mainly using highly polymorphic microsatellites. Maternal origin of the triploidy was demonstrated in most cases. To the best of our knowledge, this is the first systematic evaluation of the parental origin of chromosome sets in fetuses who survived until a cytogenetic diagnosis was established. In contrast to previous investigations this study documented a predominance of maternal origin of the extra haploid set mainly due to longer survival time for digynic triploidies. The concept of 2 distinct fetal phenotypes in triploidy is clearly supported by this study.

We report on our experience with the first 46 diagnostic chorionic villi samplings in Münster. A new echogenic plastic catheter is used. The observed abortion rate is in accordance with international experience.

We summarize our experience with chorionic villi cultures. Cell growth and chromosome analysis were successful in all cases. A significant admixture of maternal cells in chorionic villi cultures can be excluded by comparison of fluorescence polymorphisms between maternal and embryonic chromosomes.

Direct chromosome preparations were performed on placental villi obtained by ultrasound-guided needle aspiration between 18 and 37 weeks of pregnancy in 53 patients. The sampling yielded a sufficient amount of tissue with a maximum of two, and in most cases one, insertions. Placental biopsy is easily performed in cases of severe oligohydrammnios, where fetal blood sampling is usually more difficult. Direct karyotyping of placental villi is faster than chromosome analysis from fetal blood or application of the pipette method on amniotic fluid cells, and currently represents the most rapid approach to prenatal diagnosis of chromosomal abnormalities from the first to the third trimester of pregnancy.

An abstract of the article "The 22q11 microdeletion syndrome: a review of prenatal ultrasonographic findings and the relation with diagnostic prenatal testing," by T. Sarac Sivrikoz and colleagues is presented.