Amniotic fluid cells obtained by transabdominal amniocentesis at various stages of pregnancy were cultivated successfully. The intrauterine detection of Down syndrome, galactosemia, and mucopolysaccharidosis was established using the cultivated amniotic fluid cells. The use of this procedure increases the precision of genetic counseling and should stimulate the development of new approaches for the intrauterine management of genetic defects. However, until considerably more experience is gained with these techniques, the procedures should be considered experimental.
This article by Nadler marks one of the milestones in the development of the field of modern medical genetics.1Compared with many of the subspecialties of pediatrics, genetics became applicable to clinical medicine relatively late, with the discovery of the etiology of the Down syndrome2 and the other common autosomal trisomies, trisomy 183-5 and trisomy 13.4 Although recognition of the causes of these common genetic disorders was reassuring to families of the children affected and their caregivers, that knowledge neither resulted in improved medical care for the children affected nor prevented recurrences of these conditions within families at risk. It was with the development of antenatal diagnostic techniques that more options became available to families with known or suspected genetic disorders, and the field of medical genetics came into existence. Thus, it was thatPediatrics already was a respected, well established journal of 20 years when this report by Nadler was published in 1968.
The accurate prenatal diagnosis and treatment of literally hundreds of genetic disorders6 have followed Nadler's early observations. The availability of prenatal diagnosis gave rise to the field of prenatal genetics and genetic counseling. In this short report, Nadler describes the application of analysis of cultured amniocytes7 for the prenatal diagnosis of chromosome anomalies and a variety of inborn errors of metabolism. With the availability of cultured amniocytes, Nadler was able to perform direct chromosome analysis, quantitative examination of the activity of enzymes, and qualitative analysis of cellular size and structure. Along with high-resolution fetal ultrasound scanning, these techniques remain the standards for most prenatal diagnostic studies performed today.
Prenatal diagnosis of genetic disorders has vastly changed the reproductive options of families with known or suspected genetic disorders. Before the development of prenatal diagnosis, many at-risk couples opted not to have children. Prenatal diagnosis has allowed such parents to have healthy children by providing the option of pregnancy termination of affected fetuses. Prenatal diagnosis also has allowed for improved treatment of children with some genetic conditions, both prenatally and postnatally. Antenatal diagnosis of genetic disorders has paved the way for prenatal surgical repair of some congenital anomalies,8 and has increasingly allowed for prenatal biochemical treatment or gene replacement for some children with genetic disorders.9 Prenatal diagnosis also has allowed for immediate postnatal treatment of children with some genetic disorders, thereby eliminating the morbidity or mortality accompanying late diagnosis.
Dr Nadler's article presages accurately the rapid development of the field of prenatal clinical genetics: “It is extremely likely that numerous genetic disorders will be capable of being diagnosed during pregnancy, using either amniotic fluid, desquamated cells, or cultivation of amniotic fluid cells. The precise status of the fetus will allow for better obstetrical management of a specific pregnancy … In addition, if the modification of genetic defects is to become feasible, intra-uterine diagnosis becomes essential.”
He also correctly underscored the moral, legal, and ethical pitfalls that these techniques involve, specifically the abortion of children with genetic disorders. If anything, the ethical, legal, and social impact of prenatal diagnostic genetic techniques has increased in the nearly 30 years since Nadler published his observations. Understanding of this aspect of prenatal genetic diagnosis continues to lag behind the technical ability to perform the procedures involved.
The landmark observations of Dr Nadler and others led to the field of prenatal genetics, genetic counseling, and fetal therapy. In the future, additional less invasive prenatal diagnostic techniques will be perfected, including genetic analysis of fetal cells recovered from the maternal bloodstream. More accurate diagnosis of human genetic diseases by molecular genetic analysis will follow the mapping of the human genome. Finally, gene replacement therapy and other prenatal treatment modalities will be investigated further and developed for many genetic conditions currently untreatable.
- Nadler HL
- Lejeune J,
- Gautier M,
- Turpin R
- ↵Weaver DD. Catalog of Prenatally Diagnosed Conditions. Baltimore, MD: The Johns Hopkins University Press; 1989
- ↵Tanswell AK, O'Brodovich HM. The present and future role of gene therapy in the newborn. Curr Opin Pediatr. 1997;9:141–145
- Copyright © 1998 American Academy of Pediatrics