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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    1.9 Dominant genetic disorders which become manifest relatively late in life usually have a strong family history, unless affected ancestors died from another cause before the onset of the disorder. Early-onset dominant disorders such as achondroplasia are frequently due to a new genetic mutation and thus have no family history. The diagnosis of a dominant disorder in one individual implies a risk for all first-degree relatives of carrying the same pathological gene and of developing the same disease and transmitting it to their offspring (Fig 2a). 1.10 Classically, X-linked (or sex-linked) disorders show a typical family history of symptomless (healthy) female carriers giving birth to affected males. However, there may be no family history if the disorder is transmitted only in the female line for several generations or has arisen as a new mutation; this is relatively common in severe X-linked disorders (Fig 2b). The commonest of the severe X-linked disorders is fragile-X mental retardation. This is a severe disability often, but not always, associated with a visible ‘fragile site’ on part of the X-chromosome. It affects 1 in 1,000-2,000 of the population, and therefore is almost as common a cause of mental deficiency as Down’s syndrome. In this disorder a proportion of female carriers may be severely affected. Healthy female relatives of males with X-linked disorders have a high reproductive risk, and when a reliable carrier test is available many can be identihed by screening the extended family of known affected individuals. 1.11 Genes for autosomal recessively-inherited disorders are very common but the birth incidence of affected individuals depends on the frequency with which carriers of the same disorder select each other as partners (Fig 2c). Although this is a relatively uncommon event, even a low birth-rate of affected individuals (homo zygotes) indicates a sizeable reservoir of carriers of the gene (heterozygotes) (Fig 3), o o o aj CX o bD N o E o X 24 22 20 18 h 16 - 14 12 - 10 - _MSUD ,_Homocystinuria ,—Galactosaemia _PKU Congenital adrenal hyperplasia op-Antitrypsin deficiency ^Cystic fibrosis ^Haemochromatosis .Thalassaemia in Pakistanis ,_SCD in West Indians -Thalassaemia in Cypriots _SCD among West Africans 12 16 20 Carriers (% of the population) Fig 3. Relationship between the birth-rate of homozygotes with recessively-inherited conditions, and carrier frequency. The examples show that even relatively few births indicate a large number of carriers in the population. MSUD—maple syrup urine disease; PKU— phenylketonuria; SCD—sickle-cell disease.