Prenatal diagnosis

All three forms of spinal muscular atrophy are inherited as autosomal recessive disorders, linked to chromosome 5q. Prenatal diagnosis using closely linked markers is now available. A rare, autosomal dominant form of juvenile SMA is similar in expression to the recessive forms, but 5q is not involved. 

In general, the porphyrias described are inherited in an autosomal dominant manner, with the exception of congenital erythropoietic porphyria, which is inherited in a recessive mode. The precise abnormalities in the genes directing synthesis of the enzymes involved in heme biosynthesis have been determined in some instances. Thus, the use of appropriate gene probes has made possible the prenatal diagnosis of some of the porphyrias. 

If the genetic lesion is understood and a specific probe is available, prenatal diagnosis is possible. DNA from cells collected from as little as 10 mL of amniotic fluid (or by chorionic villus biopsy) can be analyzed by Southern blot transfer. A fetus with the restriction pattern AA in Figure 40-10 does not have sickle cell disease, nor is it a carrier. A fetus with the SS pattern will develop the disease. Probes are now available for this type of analysis of many genetic diseases. 

Possibility of prenatal diagnosis by appropriate enzyme assays... 

The first will constitute a general backgroimd and theoretical introduction to the subject, while the second will describe the experience which we and others have had in the application of the various techniques of prenatal diagnosis. For further background and detail, the reader is referred to several other recent reviews of the subject (2-6). 

Two types of Information can be obtained from cultured amnlotlc fluid cells. The first, which constitutes the major proportion of the work done In the area of prenatal diagnosis of genetic disorders. Is the chromosome constitution of the fetus. The second Is the biochemical status of the fetus, at least In so far as certain defined enzyme pathways are concerned. 

Is to determine the sex of the fetus the other Is to determine whether the fetus has a chromosome abnormality Fetal sex determination Is not, at present, performed so that couples can chose the sex of their baby While there may not be any significant ethical or sociological (43) reasons to oppose sex determination for this reason, the lack of sufficient facilities has made this an Indication of extremely low priority The reason for ascertaining the sex of a fetus. In so far as the prenatal diagnosis of genetic disease Is concerned. Is to determine Aether the fetus Is a male or female In situations In which the parents are at risk of having a child with an X-llnked disorder which affects only males If the fetus Is a male. It will have a 50% risk of being affected This risk. In such... 

While all chromosomal abnormalities can In principle be detected by prenatal diagnosis, fetal karyotyping Is not at present being done as a general screening procedure Rather,... 

The monitoring of pregnancies for neural tube defects Is the most recent of the Indications for prenatal diagnosis In families In which one child has been affected, the risk of recurrence Is approximately 4% Of the 16 pregnancies In which amniocentesis was done to determine the level of a-fetoprotein, no affected fetuses were found ... 

Since the Introduction of the prenatal diagnosis In San Francisco In 1970, there has been virtually an exponential Increase In the demand for this service This demand has been... 

Mllunsky, A. "The Prenatal Diagnosis of Hereditary Disorders", Charles C. Thomas, Springfield, 1973. 

Hahnemann, N. "Early Prenatal Diagnosis A Study of Biopsy Techniques and Cell Culturing from Extraembryonlc Membranes". Clin. Genet., (1974), 6, 294-306. 

H sll, P. "Microtechniques for Rapid Prenatal Diagnosis In Early Pregnancy", In Birth Defects, Proc. 4th Int. Conf., ed. A. G. Motulsky and W. Lenz, Excerpta Medlca, Amsterdam, 1974, 234-239. 

Wald, N. J. Brock, D. J. H. and Bonnar, J. "Prenatal Diagnosis of Spina Bifida and Anencephaly by Maternal Serum - Alpha-Fetoprotein Measurement. A Controlled Study". 

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