Prenatal diagnosis and genetic screening : community and service implications / a report of the Royal College of Physicians.

  • Royal College of Physicians of London.
Date:
1989
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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Prenatal diagnosis and genetic screening : community and service implications / a report of the Royal College of Physicians. Source: Wellcome Collection.

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    ‘ Retrospective’ carrier diagnosis ‘Prospective ’ carrier diagnosis fear of handing on the undesirable gene. However, carrier detection in dominant disorders amounts to preclinical diagnosis for the person at risk, and in the absence of effective treatment the major psychological implications of such a diagnosis mean that it must always be undertaken by experts. So far, there has been a very cautious uptake of carrier detection for Huntington’s chorea. Prenatal diagnosis, seemingly impossible if the parents’ carrier status is unknown, can be done in many cases by ‘exclusion testing’ using DNA analysis methods to confirm that a fetus is unaffected [ 12 ]. 2.27 The diagnosis of a male with an X-linked disorder, for example haemophilia, places several female relatives at recognised risk of being carriers. Since healthy (ie symptomless) female carriers are not themselves at risk for the disorder, such women are often interested in carrier testing. DNA analysis methods, especially useful for detection of Duchenne muscular dystrophy and haemophilia, provide more reliable prediction than the classical biochemical methods. One of the main advantages of the DNA method has proved to be the restoration of reproductive confidence to women with a family history of an X-linked disorder who are shown not to be carriers. 2.28 The potential of carrier detection and prenatal diagnosis for reducing the incidence of dominant and X-linked diseases is restricted by the limitations of the family history and by the relatively high incidence of new mutations in some groups of disorders. For example, only about two-thirds of cases of Duchenne muscular dystrophy could be prevented in this way. However, taking the above factors into account, and assuming steady progress in developing genetic services, prenatal diagnosis might reduce the incidence of all severe dominant and X-linked disorders by up to 50%. 2.29 Cystic fibrosis is the most common recessively-inherited disease in the UK. Prenatal diagnosis for this condition is now possible by assay of amniotic fluid alkaline phosphatase at about 19 weeks’ gestation [13], or by DNA analysis in the first trimester [14]. Although there is an increasing demand for this service, it can have only a small effect on the birth-rate of affected children. This is because no carrier testing yet exists and prenatal diagnosis can be offered to couples only after the birth of their first affected child, ie ‘retrospectively’. However, because final family size is small, most families will contain only one affected child. Prenatal diagnosis can make a major numerical impact on cystic fibrosis only when reliable direct carrier detection is possible. 2.30 When a carrier test exists for a common recessively-inherited disease, as it does at present for the haemoglobin disorders and Tay-Sachs disease, couples at risk can be identified by screening the whole population before they have children, ie ‘prospectively’. When most prospectively-detected couples at risk request prenatal diagnosis, as is the case for thalassaemia, there can be a drastic fall in the birth-rate of affected infants (see Fig 7). This is why the development of carrier testing for cystic fibrosis is so urgently required. 2.31 Techniques for screening for inherited disease are evolving rapidly. When questions arise of whether carrier testing or prenatal diagnosis is possible for a particular condition, it is essential to seek up-to-date information from the local clinical genetics centre. 2.32 The birth-rate ofinfants with inherited disorders wifi fall steadily over several generations if adequate resources are provided for population-screening, meticulous establishment of genetic registers, conscientious pursuit of family studies, and for genetic counselling including the offer of prenatal diagnosis.