Chromosomal abnormalities in fetuses with open neural tube defects: prenatal identification with ultrasound.

OBJECTIVES: To determine the prevalence of chromosomal abnormalities in fetuses with open neural tube defects (NTD) undergoing prenatal chromosome analysis. The role of prenatal ultrasound in detecting those with an underlying chromosomal abnormality was also investigated. METHODS: Over a 6-year period, 144 fetuses with open NTD underwent prenatal chromosome analysis between 12 and 37 weeks of gestation, as part of a prospective, multicenter prenatal diagnosis and counseling program in Chile. This population included 66 fetuses with spina bifida, 46 with acrania/anencephaly, 21 with cephalocele and 11 with iniencephaly. A confident prenatal diagnosis was made in 143 fetuses (99%) and confirmed postnatally in all cases. RESULTS: An underlying chromosomal abnormality was diagnosed in 10 fetuses (7%), six with spina bifida, three with cephalocele and one with craniorachischisis. The prevalence of chromosomal abnormality varied according to the defect present in the fetus, with a 14% (3/21) prevalence among those with cephalocele, 9% (6/66) among those with spina bifida and 2% (1/57) among those with lethal defects such as acrania, anencephaly or iniencephaly. Karyotype results revealed trisomy 18 in seven cases, trisomy 13 in two and mosaicism for a marker chromosome in one. Prenatal ultrasound before the procedure showed that all chromosomally abnormal fetuses had additional findings. The prevalence of chromosomal abnormality in fetuses with spina bifida and cephalocele was higher when chromosome analysis was performed at or before 24 weeks of gestation in comparison to those performed after 24 weeks (5/31 (16%) vs. 4/56 (7%), respectively). However, this difference did not reach statistical significance, probably due to the small number of cases. CONCLUSIONS: A significant number of fetuses with open NTD are chromosomally abnormal. Although prenatal chromosome analysis should be considered in all cases, prenatal ultrasound seems effective in identifying those fetuses with an underlying chromosomal abnormality.

Prenatal ultrasound findings in complete trisomy 9.

OBJECTIVE: To report on the prenatal ultrasound findings associated with complete trisomy 9. METHODS: Cases of complete trisomy 9 diagnosed prenatally were identified by reviewing the reports from two large cytogenetics laboratories serving tertiary referral centers for prenatal diagnosis. Information on prenatal ultrasound findings and outcome was obtained in all cases. RESULTS: Nine cases of complete trisomy 9 were identified. The diagnosis was made in the first trimester in four cases, in the second trimester in three and in the third trimester in two. Two fetuses underwent first-trimester ultrasound screening for aneuploidy and the nuchal translucency thickness was increased in both. All five fetuses detected in the second and third trimesters had several fetal anomalies including Dandy-Walker malformation in four cases, facial dysmorphism in four, genitourinary anomalies in three, congenital heart defects in three, ventriculomegaly in three, abnormal hands in two and megacisterna magna in one. Four fetuses were growth-restricted at the time of ultrasound evaluation. However, the two cases diagnosed in the third trimester had routine second-trimester anomaly scans reported as normal. There were no survivors in this series. CONCLUSION: Fetuses with complete trisomy 9 have multiple anomalies that can be readily detected prenatally by ultrasound. These mainly include, but are not restricted to, craniofacial, cardiovascular, musculoskeletal and genitourinary malformations. However, findings can be subtle and therefore missed at the routine second-trimester scan.

Nuchal translucency thickness and outcome in chromosome translocation diagnosed in the first trimester.

In order to determine the significance of nuchal translucency thickness on the subsequent natural history of first-trimester fetuses with a chromosome translocation, seven consecutive cases diagnosed between 11 and 13 weeks of gestation were reviewed. Nuchal translucency measurements were successfully obtained before chorionic villus sampling (CVS) in all cases. Three fetuses had an unbalanced translocation and all were associated with increased nuchal translucency and multiple anomalies at the detailed second-trimester scan. There were no survivors in this group. The remaining four fetuses had a balanced translocation; all had normal nuchal translucency thickness and no structural anomalies were detected in the second trimester. Three of these fetuses were born at > or =35 weeks of gestation and were phenotypically normal. However, an unexpected single fetal demise occurred in a dichorionic twin pregnancy at 28 weeks of gestation. It is concluded that nuchal translucency measurements provide important prognostic information on pregnancy outcome in first-trimester fetuses with a chromosome translocation. In parents with a known balanced translocation, the detection of increased nuchal translucency at 11-14 weeks of gestation is associated with unbalanced translocations, structural anomalies and poor pregnancy outcome.

Accuracy of the haemoglobin alkaline denaturation test for detecting maternal blood contamination of fetal blood samples for prenatal karyotyping.

The haemoglobin alkaline denaturation test was routinely performed in 183 fetal blood samples obtained by cordocentesis for prenatal karyotyping by adding 0.1 ml of the blood into a glass test tube containing 5 ml of water and 0.3 ml of 10 per cent KOH as the alkali reagent. The mixture was agitated gently and read at 2 minutes, at which time it was interpreted as a pure fetal blood sample or contaminated with maternal blood according to the change in colour. In order to determine the accuracy of this test to detect maternal blood contamination, the results were compared with the number of fetal and maternal cells detected by standard cytogenetic techniques in those blood samples obtained from male fetuses (n=97). Among these samples, the haemoglobin alkaline denaturation test gave an adult haemoglobin reaction in two cases (2.1 per cent); both samples showed different degrees of maternal 46,XX cells in the metaphases examined (29 of 30 cells in one case and 2 of 31 cells in the other). Conversely, of the 95 samples which gave a fetal haemoglobin reaction, the cytogenetic analysis did not reveal any maternal cells in the metaphases analysed (median 30 cells, range 20-65). We concluded that the haemoglobin alkaline denaturation test is an accurate method for excluding clinically significant maternal blood contamination of fetal blood samples obtained for prenatal karyotyping. This simple, inexpensive technique provides immediate information and, therefore, can be safely incorporated as a bedside test for analysis during fetal blood sampling procedures.

Prenatal diagnosis of nonmosaic trisomy 9 in a fetus with severe renal disease.

We report a case of nonmosaic trisomy 9 presenting at 21 weeks of gestation with polycystic, echogenic horseshoe kidney, collapsed bladder, absent amniotic fluid, and intrauterine growth restriction. Color Doppler imaging demonstrated no blood flow signals from renal vessels. Fetal blood sampling confirmed a 47,XX,+9 karyotype, with no evidence of mosaicism, and increased serum beta2-microglobulin levels of 10.7 mg/l, consistent with severe renal failure. A repeat scan at 23 weeks also revealed a dysmorphic face, bilateral microphthalmia, and a cerebellar vermian defect. Follow-up examinations showed progressive growth restriction leading to fetal death at 33 weeks of gestation. This report demonstrates that fetuses with nonmosaic trisomy 9 may present with severe renal abnormalities and confirms that cases seen in the second and third trimesters usually have a dismal outcome.

Sex chromosome pentasomy (49,XXXXY) presenting as cystic hygroma at 16 weeks' gestation.

The pentasomy 49,XXXXY is one of the rarest sex chromosome defects, occurring with an estimated incidence of 1 in 85 000 male births. This condition is associated with pre- and postnatal growth deficiency, severe mental retardation, hypogenitalism, and other skeletal, facial and cardio-vascular anomalies. In this report we present such a case diagnosed prenatally by chorionic villus sampling after the ultrasound detection of cystic hygroma at 16 weeks' gestation. Although the prenatal diagnosis of cystic hygroma and its association with aneuploidy has been documented in numerous reports, sex chromosome aneuploidy, other than the 45,X karyotype, accounts for only 0.3 per cent of cases.

Pseudocyst of the umbilical cord: prenatal sonographic appearance and clinical significance.

OBJECTIVE: To assess the clinical significance of umbilical cord pseudocysts detected prenatally by sonography. METHODS: The prenatal sonographic findings, karyotype, and perinatal outcome in 13 fetuses with umbilical cord pseudocysts were reviewed retrospectively. RESULTS: Umbilical cord pseudocysts were diagnosed at a median gestation of 27 weeks (range 15-37). Pseudocysts were single in eight cases with cyst diameters ranging from 20 to 50 mm, and double in one case. In the remaining four cases, multiple small cystic masses measuring less than 8 mm were identified. Additional sonographic findings were noted in 11 cases; ten of these fetuses had prenatal karyotyping, which showed trisomy 18 in five cases, trisomy 13 in one case, and a 46,XX, inv ins(18;21) complement in one case. Among the seven chromosomally abnormal fetuses, umbilical cord pseudocysts were multiple in four fetuses and single in three. All chromosomally abnormal fetuses and two euploid fetuses with associated structural defects died in utero or in the neonatal period. There were no perinatal complications in either of the fetuses with isolated pseudocysts. CONCLUSION: The prenatal sonographic appearance of umbilical cord pseudocysts varied widely. These umbilical cord cystic masses were associated strongly with chromosomal disorders and structural defects, regardless of their sonographic appearance in utero.

Twin pregnancy discordant for trisomy 14 mosaicism: prenatal sonographic findings.

The survival of infants with trisomy 14 mosaicism has been scarcely reported in the literature, with only 15 cases being documented up to 1992. We present a case of a dichorionic twin pregnancy in which prenatal sonography at 24 weeks' gestation showed that one of the twins had several anomalies including intrauterine growth restriction, alobar holoprosencephaly, a cleft lip and palate, a recessive chin, a small stomach, overlapping fingers, a ventricular septal defect, and polyhydramnios. Twin 2 was structurally normal. In view of the lethal condition and associated polyhydramnios affecting one of the twins, prenatal surveillance for signs of tense polyhydramnios and premature labour was undertaken. The pregnancy proceeded uneventfully until 37 weeks, at which time a Caesarean section was performed. At birth, neonatal blood from the abnormal twin confirmed trisomy 14 mosaicism in 12 per cent of lymphocytes. The infant died on day 36 of life.

[Spontaneous abortion: cytogenetic study of 609 cases]. / Aborto espontáneo: estudio citogenético en 609 casos.

Chromosomal abnormalities are the most frequent cause of first trimester spontaneous abortions (SA). During the period September 1989 through May 1996 we have cytogenetically studied 640 embryonic tissue samples obtained from cases of SA. Of these, 609 samples (95.1%) were successfully karyotyped. An abnormal karyotype was observed in 388 cases (63.7%). The sex ratio (XY/XX) was 1.03. There was no difference of this ratio between cytogenetically normal and abnormal embryos. The most frequent abnormalities detected were autosomal trisomies (239/388 [61.6%]) followed by triploidy (62 cases, 16%), monosomies (41 cases, 10.6%) and tetraploidy (17 cases, 4.4%). The single most common anomaly observed was trisomy 16 (73 cases, 18.8%). The frequency of trisomies, with the exception trisomy 16, was related with advanced maternal age.

[Clinical and cytogenetic analysis of 257 cases of Down's syndrome]. / Análisis clínico y citogenético en 257 casos de síndrome de Down.

Among 257 patients with clinical diagnosis of Down's syndrome, 56.4% of male gender, in whom cytogenetic studies were performed, 14 (5.4%) had normal karyotypes and 243 (94.6%) had 21 trisomy. Of these last, 225 (92.6%) had free 21 trisomy, 10 (4.1%) showed mosaics, 8 (3.3%) had translocations. Average maternal age of this sample was significantly higher than that of patients attending the same maternity wards (32.14 vs. 24.85 years) and 41% of Down syndrome's patients came from mothers aged 36 years or more, even though only 9.7% of this country's deliveries proceed from women of that age group. As to seasonal occurrence, the proportions of births which happened in summer almost doubled that of winter (33.1% vs. 16.9%). The frequency of characteristic clinical signs of Down's syndrome was somewhat different than that described for patients from some other countries, for instance: epicanthus, short neck and widening of the space between 1st. and 2nd. toe were more frequent, while Brushfield's spots, depressed occiput, dental anomalies, heart malformations and fissured tongue seemed less frequent. The importance of cytogenetic studies for diagnosis and genetic counseling is stressed.

[Cytogenetic study of acute and chronic leukemias]. / Estudio citogenético en leucemias agudas y crónicas.

From 1983 to 1987 we studied 30 patients with leukemia searching for chromosomal alterations. Cytogenetic studies of bone marrow showed an abnormal karyotype in 19 (67%). Seven out of 14 cases of acute leukemia presented different chromosomic alterations. The Philadelphia chromosome was found in 11 patients with chronic myeloid leukemia and 3 patients with chronic lymphatic leukemia; a Pseudo-Philadelphia chromosome was present in one patient, this being the first such finding in Chile. Thus, the karyotype is a valuable complementary study not only in chronic myeloid leukemia but also in chronic lymphatic leukemia and the acute lymphoblastic and non-lymphoblastic varieties.

Contribuición del laboratorio de citogenética al estudio de enfermedades hematológicas / Cytogenetic laboratory contribution to the study of hematologic disease

Se realizó estudio citogenético de médula ósea en 25 pacientes con alteraciones hematológicas malignas o premalignas. En 22 pacientes se obtuvo células en mitosis para análisis cromosómico (88%). En 10 pacientes (40%) se observó un cariotipo alterado en algún momento de su evolución. La alteración cromosómica más frecuente fue la presencia de un cromosoma Philadelphia (Ph') en seis pacientes, cinco de los cuales tenían un diagnóstico de leucemia mieloide crónica (LMC). El resto de los pacientes con cariotipo alterado tenía un diagnóstico de preleucemia. Dos de ellos tenían células poliploides, en uno se encontró cromosomas marcadores y en otro, un cromosoma 22q+