The antenatal detection of genetic disorders. Current status and future prospects.

Abstract

With the onset of prenatal diagnosis genetic counseling has assumed new dimensions. A family can now have its own children without fearing the birth of a child with a specific serious genetic disease. Prenatal diagnosis of most genetic defects requires amniocentesis. Appropriate genetic counseling must precede the amniocentesis. Most prenatal detection programs will not determine fetal sex unless a specific indication exists. Chromosome disorders are responsible for many birth defects and reproductive stage. The incidence of chromosome aneuploidy has been estimated to be .59% of newborns with a total of 149 major chromosomal abnormalities. This incidence rises to 5.8% of the perinatal death population and to 32.2% of the children studied because of suspected cytogenetic abnormality. The most common indication for prenatal diagnosis is advanced maternal age. The frequency of Downs syndrome has been related to maternal age but not to paternal age. Women over age 35 should receive genetic counseling regarding the risks of having a child with Trisomy 21 and the risks of amniocentesis. The 2nd most common indication for prenatal diagnosis is for women who have previously borne a child with Trisomy 21. The recurrence risk appears to be 1-2% irrespective of maternal age. Fetal sex determination is achieved by demonstration of X-chromatin Y-chromatin and by fetal karyotyping. Amniotic fluid cells can be stained directly for the X- or Y-chromatin with an accuracy of 95% but a full karyotype is more accurate. Women who are carriers of X-linked disorders can have the fetal sex determined and have male fetuses aborted. In Fabrys disease Hunters syndrome and the Lesch-Nyhan syndrome all of which are enzymatically defined an affected male can be distinguished from an una ffected male. In all other conditions such as hempohilia or Duchenne m uscular dystrophy 50% of male abortuses would not have the disease. In herited biochemical disorders of metabolism occur in .8% of liveborns. Most congenital malformations occur without demonstrable chromosomal or biochemical abnormalities and are produced by a combination of environmental genetic factors. Ultrasound measurements of the biparietal diameter of the fetal head have been used to diagnose anencephaly. Other experimental diagnostic methods are mentioned. Complications of amniocentesis have been few but failure to obtain satisfactory results has been more common. Prenatal diagnosis is not infallible. The emotional trauma to the parents may be important. Artificial insemination using a sperm donor has been proposed to avoid inherited disease. Future advances in prenatal diagnosis are predicted.