Prenatal diagnosis of inverted duplicated 8p.

The phenotype of inverted duplicated 8p, region 8p11.2-p23, reported in children and adults, includes: severe mental retardation, minor facial anomalies, agenesis of corpus callosum, and other malformations including those of heart and kidneys. We report on the prenatal diagnosis of 2 cases of inverted duplication 8p. Both cases were ascertained by abnormal level 2 ultrasound findings. Case 1 presented at 16.5 weeks of gestation with massive distention of the fetal bladder, bilateral hydronephrosis, abnormality of the lower lumbar spine, absence of the sacral spine and a Dandy-Walker variant (interhemispheric cyst and enlarged third ventricle). Case 2 presented at 30 weeks of gestation with agenesis of corpus callosum, slightly enlarged lateral ventricles, interhemispheric cyst and enlarged third ventricle, and possible coarctation of the aorta. The intracranial and cardiac anomalies were confirmed and further defined after delivery. Cytogenetic analysis in both cases showed additional material on 8p. In both cases, fluorescence in situ hybridization (FISH) defined the abnormal chromosome, as a pseudodicentric chromosome with duplication of the short arm from centromere to p23 and deletion from p23 to pter. Our findings support those of prior reports of the inverted duplicated 8p chromosome with multiple anomalies and add prenatal findings to our knowledge.

Ultrasound detection of fetal aneuploidy in patients with elevated maternal serum alpha-fetoprotein.

Increasing confidence in the ability of high-resolution ultrasound to detect neural tube and ventral wall defects has enabled us to offer a revised risk estimate to the patient with an elevated maternal serum alpha-fetoprotein (MSAFP) level, such that amniocentesis may not be necessary. Recent authors have suggested that a reduced emphasis on follow-up amniocentesis fails to consider an increased risk for chromosomal anomalies in pregnancies with an elevated MSAFP, and that amniocentesis should still be performed. We reviewed our ultrasound findings from patients who underwent amniocentesis for evaluation of an elevated MSAFP and who had a karyotype prepared from the amniotic fluid sample. Four abnormal karyotypes were detected among 313 amniocenteses, and three of these were correctly predicted based on an abnormal ultrasound. The risk of an unexpected fetal aneuploidy after a normal consultative ultrasound in our series was one in 310. This is comparable to the risk of detecting abnormal chromosomes in the fetus of a 32-year-old woman, an age at which amniocentesis is not routinely offered.

Prenatal diagnosis of cystic fibrosis by chorionic villus sampling using 12 polymorphic deoxyribonucleic acid markers.

This report describes the application of a genetic prenatal diagnostic test for cystic fibrosis to a family with a cystic fibrosis-affected child. The test uses 12 deoxyribonucleic acid (DNA) markers that bracket the cystic fibrosis gene on chromosome 7, and chorionic villus tissue as a source of DNA from the fetus at risk for cystic fibrosis. The fetus was predicted by DNA analysis to be unaffected (although a carrier of one cystic fibrosis gene); this diagnosis was confirmed postnatally by the standard sweat electrolyte test. The genetic linkage test is informative in more than 99% of families with cystic fibrosis-affected members and is also useful for determination of carrier status. The test is both more informative and more accurate than one based upon the markers Met and D7S8 (J3.11) alone. The analysis can be done directly from chorionic villus tissue, and therefore can provide a diagnosis as early as nine to 12 weeks after conception.