Prenatal diagnosis and screening

Abstract

We have limited the scope of this article to those disorders that have already been successfully diagnosed or excluded in utero. We currently have the potential to diagnose a number of others for which the opportunity has not yet arisen. If a biochemical, morphologic, chromosomal, or DNA alteration is known for a specific condition and is likely to be expressed in one of the fetal tissues or secretions, attempt at prenatal diagnosis is reasonable. Our ability to detect the inherited disorders of the skin in utero will continue to improve both in the number of specific disorders successfully diagnosed or excluded and in the increasingly earlier stages of pregnancy at which the disorder can be detected. Advances in instrumentation will, it is hoped, decrease the risk of the invasive methods of prenatal diagnosis, and improvement in noninvasive methods, such as maternal serum screening, may eliminate the need for invasive procedures altogether. Detection of useful DNA polymorphisms linked to genes for specific genodermatoses and development of specific gene probes will improve the accuracy of diagnosis and reduce the need for specific fetal tissues. The entire genome of an individual is present in each cell, even though a specific gene product may not be expressed in that cell. Thus, DNA restriction endonuclease studies can be performed on amniotic fluid cells, chorionic villi, fetal cells in maternal circulation, and fetal tissues with equal facility. The usefulness of prenatal diagnosis will always be limited by the ability to detect pregnancies at risk. If carrier detection is unavailable, the only way to identify couples at risk for offspring with an autosomal recessive condition is by the birth of an affected child. For autosomal dominant and X-linked recessive and dominant conditions, new mutations will continue to occur. As mentioned previously, screening of all pregnancies for all defects is not possible now and is unlikely ever to be feasible, either economically or technically. The reliability of prenatal diagnosis will continue to depend upon accurate diagnosis in the index case and upon the availability of a specific and sensitive test (or tests), with no overlap in values between heterozygotes and homozygotes for autosomal recessive conditions or between normal and affected fetuses with autosomal dominant and X-linked recessive disorders. Correct interpretation of test results is subject to experience, recognition of artifact, and variation in the expression of a given disorder in utero.(ABSTRACT TRUNCATED AT 400 WORDS)