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Biomedical subjects

C M Gosden

Publications and source records attributed to C M Gosden.

At least 19 recordsLinked to original sources
PubMed1992

Ultrasonographically detectable markers of fetal chromosomal abnormalities.

Screening for fetal chromosomal abnormalities on the basis of maternal age has not resulted in a substantial fall in the proportion of infants born with an abnormal karyotype. Most fetuses with major chromosomal abnormalities have defects that can be recognised on detailed ultrasonographic examination. Therefore, provided the cardinal signs of each chromosomal syndrome are recognised, it is possible that screening by ultrasound examination could have a greater impact. We karyotyped 2086 fetuses after ultrasonographic examination had revealed fetal malformations, growth retardation, or both. Chromosomal abnormalities were detected in 301 (14%) cases and were more common among fetuses with multisystem malformations (29%) than among those with isolated defects (2%). The commonest chromosomal abnormality was trisomy 18, followed by trisomy 21, triploidy, Turner's syndrome, unbalanced chromosomal rearrangements, and trisomy 13. Trisomy 18 was associated with strawberry-shaped head, choroid plexus cysts, facial cleft, micrognathia, heart defects, exomphalos, malformations of hands and feet, and growth retardation. In trisomy 21, the associated defects were subtle and included nuchal oedema, macroglossia, atrioventricular septal defects, mild hydronephrosis, clinodactyly, and sandal gap. The frequency of autosomal abnormalities increased with maternal age, but if fetal karyotyping had been restricted to mothers older than 35 years, large proportions of chromosomally abnormal fetuses would not have been diagnosed prenatally (64-97%). Our findings provide guidelines as to which defects to search for in screening studies for the detection of chromosomal abnormalities.

Adolescent↗
PubMed1992

Fetal nuchal oedema: associated malformations and chromosomal defects.

During an 8-year period, oedema in the dorsal cervical region that produces a characteristic tremor on ballotement of the fetal head (nuchal oedema) was observed in 145 (7%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. Nuchal oedema was distinguished from nuchal cystic hygromata and from hydrops foetalis. In 132 (91%) of the cases with nuchal oedema, there were other fetal malformations, and 53 (37%) fetuses had chromosomal abnormalities, mainly trisomy 21 but also other trisomies, deletions or translocations, triploidy and Turner syndrome. Furthermore, the chromosomally normal fetuses with nuchal oedema had a very poor prognosis because, in many cases, there was an underlying skeletal dysplasia, a genetic syndrome or cardiac defect.

Abnormalities, Multiple↗
PubMed1992

Strawberry-shaped skull in fetal trisomy 18.

During an 8-year period, a strawberry-shaped skull (flattening of the occiput with pointing of the frontal bones), was observed in 54 (3%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. In all 54 cases with a strawberry-shaped skull, there were other fetal malformations; in 43 (80%) fetuses, there was trisomy 18 and in 1 triploidy. Therefore, the ultrasonographic finding of a strawberry-shaped skull should initiate a diligent search for the presence of other markers of trisomy 18 and is a strong indication for fetal karyotyping. However, in the total series of 2,086 fetuses with malformations and/or growth retardation, there were another 40 fetuses with trisomy 18 and 41 with triploidy who did not have a strawberry-shaped skull.

Abnormalities, Multiple↗
PubMed1990

Choroid plexus cysts and chromosomal defects.

During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts.

Abnormalities, Multiple↗
PubMed1989

Sexing the human fetus and identification of polyploid nuclei by DNA-DNA in situ hybridisation in interphase nuclei.

Samples of human adult lymphocytes, fetal lymphocytes, amniotic fluid cells, and chorionic villus cells were sexed independently by cytogenetics and DNA-DNA in situ hybridisation to a tritiated Y probe. For the in situ hybridisation analysis, the presence of Y bodies (hybridisation bodies) in 100 interphase nuclei were scored after autoradiography. In all, 82/83 samples were sexed in this way (one technical failure) and 78/82 were sexed by both in situ hybridisation and cytogenetics. There was complete agreement between the two methods. There was a considerable variation (40-100%) in the percentage of interphase nuclei with a hybridisation body among the male samples, but very few nuclei from female samples showed significant hybridisation. In situ hybridisation could be used to sex the conceptus when males but not females are at risk for various X-linked genetic disorders and may also be useful for detecting 45,X/46,XY mosaicism or polyploid/diploid mosaicism. This would be particularly useful for direct preparations of chorionic villus samples, which often prove difficult to analyse cytogenetically but offer the best means of avoiding maternal contamination. Some interphase nuclei had more than one hybridisation body, and this was most commonly found among amniotic fluid cells. Comparison of sizes of nuclei with one or two hybridisation bodies strongly suggested that most of the amniotic fluid cell nuclei with two hybridisation bodies were tetraploid.

Adult↗
PubMed1989

Mean red cell volume in normal, anemic, small, trisomic and triploid fetuses.

A reference range for fetal mean red cell volume (MCV) with gestation was established from the study of samples obtained by cordocentesis from 466 pregnancies undergoing prenatal diagnosis for non-erythrocyte abnormalities. The mean MCV decreased from 145 fl at 16 weeks to 113 fl at 36 weeks of gestation. Alterations in MCV were investigated in 154 red cell isoimmunized and 231 small for gestational age (SGA) fetuses. In red cell isoimmunization, significant macrocytosis was observed when the fetal hemoglobin concentration deficit was greater than or equal to 6 g/dl. In the chromosomally normal SGA fetuses (n = 178), the MCV was increased and the magnitude of macrocytosis was significantly associated with gestation and the degrees of fetal 'smallness' and fetal hypoxemia. However, the most severely macrocytotic SGA fetuses were those with triploidy (n = 22). In the SGA fetuses with other chromosomal defects (n = 31), the MCV was higher than the controls but lower than that of the chromosomally normal hypoxemic fetuses. It is suggested that in severe growth retardation there is developmental delay in the normal evolution from hepatic to medullary hemopoiesis and this is most marked in triploid fetuses. In contrast, in red cell isoimmunization the switch to medullary erythropoiesis is normal, but in severe anemia there is secondary recruitment of hepatic erythropoiesis.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

Prenatal diagnosis of congenital diaphragmatic hernia: associated malformations and chromosomal defects.

In 36 fetuses with congenital diaphragmatic hernia (CDH) diagnosed at 18-36 weeks' gestation, detailed ultrasound examination was performed for the detection of associated malformations and assessment of the likelihood of pulmonary hypoplasia. In all cases karyotyping was undertaken in blood samples obtained by cordocentesis. In 11 (31%) fetuses there were lethal chromosomal abnormalities and in 6 (17%) of the chromosomally normal fetuses there were additional lethal malformations. Of the 17 fetuses with isolated CDH and where the pregnancy was not electively terminated. 9 (60%) survived and 6 (40%) died in the neonatal period due to pulmonary hypoplasia. The presence or absence of polyhydramnios, fetal breathing movements, mediastinal shift and thoracic position of the stomach were not useful in predicting postnatal outcome.

Abnormalities, Multiple↗
PubMed1988

Linkage heterogeneity and fragile X.

A multipoint test of heterogeneity on published data from 57 families with the fragile X syndrome has been undertaken. The hypothesis being tested was that there are two loci coding for fragile X expression, mutations at either of which can produce the phenotype. No predivision of the families was undertaken, as the test used an admixture parameter. Maximum likelihoods of the hypothesis have been calculated and compared with those produced on assuming a single locus for fragile X. The data do not suggest that there are two such loci within the interval between probes 52a and St14. In particular, the large kindred published by Camerino et al. (1983) does not supply convincing evidence of heterogeneity under this test. It is argued that the observed heterogeneity between factor IX and fragile X must have another explanation. There is some evidence for a second locus for fragile X outside the interval noted above; this locus being most probably proximal to these probes. The majority of the data suggesting this result comes from a family published by Davies et al. (1985).

Fragile X Syndrome↗
PubMed1987

Prenatal diagnosis of the fragile X syndrome using fetal blood and amniotic fluid.

Nineteen pregnancies at risk for the Martin-Bell syndrome have been monitored during the second trimester for the presence of the fragile Xq27. Of the 19 potential carrier mothers, 14 showed the presence of the fragile X in their lymphocytes at a level of 4 per cent or above. As one was a twin pregnancy, fetal blood was obtained at fetoscopy from 20 fetuses and amniotic fluid obtained simultaneously from 19 of them. Of the 20 fetuses, 18 were males (including both of the twins) and two were females. Of these 18 males, seven were found to carry the fragile Xq27 in lymphocytes and subsequently six of the seven were terminated. The diagnosis was confirmed in five of the six terminated fetuses (the sixth case was a patient whose pregnancy was terminated abroad) and also in a full-term male baby. Five of the seven males without the marker X who came to term had their karyotypes confirmed post natally. Of the two female fetuses one was found to be a carrier of the fragile X and the other was not. Both babies had full-term deliveries and both had their karyotypes confirmed post natally. In some cases the diagnosis made in fetal lymphocytes was confirmed later in amniocytes.

Adult↗
PubMed1987

Ten families with fragile X syndrome: linkage relationships with four DNA probes from distal Xq.

We present clinical, cytogenetic, and linkage data of four DNA probes from the terminal long arm of the X chromosome in ten new families with fragile X syndrome. A prior/posterior method of multipoint linkage analysis is employed to combine these results with published data to refine the linkage map of terminal Xq. Ten possible probe/disease orderings were tested. The order with the greatest posterior probability (0.78) of the five loci is 52a-F9-fragile X gene-DX13-St14, although the order with reversal of the positions of 52a and F9 has a posterior probability 0.15. The mean estimates of the distances between the probes and the fragile X gene are 38 cM and 33 cM for the proximal probes 52a and F9, and 8 cM and 12 cM for the distal probes DX13 and St14. Although the current method of choice in the prenatal diagnosis and carrier detection of the fragile X syndrome remains detailed cytogenetic analysis, consideration is given to the potential role of these DNA probes, both singly and in pairs.

Chromosome Banding↗
PubMed1986

Rapid karyotyping in non-lethal fetal malformations.

Pure fetal blood samples were obtained fetoscopically, at 16-36 weeks' gestation, from 118 pregnancies complicated by ultrasonographically demonstrable fetal anomalies. Cytogenetic analysis of fetal lymphocytes yielded results within two to four days. Chromosomal abnormalities were found in 12 of 37 fetuses with non-haemolytic hydrops fetalis, 8 of 12 with exomphalos, 1 of 3 with duodenal atresia, 9 of 39 with obstructive uropathy, 1 of 3 with unilateral pleural effusion, 2 of 10 with severe growth retardation and oligohydramnios, 2 of 9 with isolated hydrocephalus, and 3 of 4 with choroid plexus cysts (of the last 4, 1 also had obstructive uropathy and 1 exomphalos). 3 fetuses with gastroschisis were cytogenetically normal. The results suggest that rapid fetal karyotyping is advisable in all cases of non-lethal or potentially correctable fetal malformations detected sonographically during the second or third trimester of pregnancy.

Chromosome Aberrations↗
PubMed1986

Prenatal diagnosis of bullous ichthyosiform erythroderma: detection of tonofilament clumps in fetal epidermal and amniotic fluid cells.

The prenatal diagnosis of bullous ichthyosiform erythroderma (BIE) has been achieved at 20 weeks' gestation by electron microscopic identification of a pathognomonic cytoskeletal abnormality within fetal epidermal cells obtained by fetoscopic skin biopsy. The same abnormality was also observed in skin derived amniotic fluid cells. The question whether amniocentesis might be used instead of fetoscopy for future prenatal detection of BIE is discussed.

Actin Cytoskeleton↗
PubMed1985

Fetoscopy in the assessment of unexplained fetal hydrops.

Pure fetal blood samples, obtained fetoscopically from 30 patients with unexplained fetal hydrops at 16 to 32 weeks gestation were investigated for cytogenetic, haematological, biochemical and virological properties. In two patients with oligohydramnios, the fetoscope was introduced transabdominally into the fetal peritoneal cavity and sampling was undertaken from the intra-abdominal portion of the umbilical vein; in all the other patients an umbilical cord vessel was sampled. Ten (33%) of the fetuses had chromosomal abnormalities, one an erythroblastic process, possibly erythroleukaemia, one alpha-thalassaemia and one cytomegalovirus infection. Blood-film abnormalities were seen in 23 (88%) of 26 fetuses that had this examination. Biochemical analysis of fetal plasma was undertaken in 18 fetuses and hypoproteinaemia was found in all cases. One fetus was subsequently found to have a paroxysmal tachyarrhythmia that responded to digitilization. Three (10%) of the fetuses survived.

Adolescent↗