Genetic studies in mental subnormality.

Date:
1973
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Genetic studies in mental subnormality. Source: Wellcome Collection.

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    Part II The Application of Genetic Principles to Screening for Metabolic Disorders The Leybourne Grange Survey of Mentally Subnormal Siblings By PETER N. SWIFT, PHILIP F. BENSON and JOHN D. STUDDY I Introduction The advances that have led in recent years to a better understanding of the causes of mental subnormality have been made possible to a large extent by progress and refinements in the biochemical field. Some conditions previously recognized as clinical syndromes have now been explained, but many more await solution. The initial step towards this end is the identification and separation of disorders arising from specific genetically determined metabolic defects from the heterogeneous mass of conditions resulting in mental subnormality. From the rarity with which known metabolic disorders of recessive inheritance are encoun¬ tered it is likely that those which have not yet been recognized will also occur with extreme rarity. However, frequency of inherited meta¬ bolic defects will depend on selection criteria of the population which is studied. For example, the prevalence of phenylketonuria has been assessed as о • о i per cent in newborn infants in the United States (Guthrie and Susi, 1963), and as о -64 per cent (Jervis, 1954) and 2 -4 per cent (Carson, 1965) in mentally retarded children, but where there is more than one retarded sibling in the family, as might be expected, the incidence has been found to be higher (e.g. 5-5 per cent; Wright et al., 1961). Two main procedures for screening are available, the clinical and the biochemical. The clinical approach has long been and is still a most important diagnostic procedure. However, it has its limitations by reason of its dependence on the skill of one or a small number of observers whose combined experience over several years may be insufficient to enable them to recognize that a certain association of features represents a syndrome and is not a chance occurrence. Furthermore, some cases of mental subnormality due to metabolic disorders may show no other constant physical or mental abnormality upon which a clinical diagnosis can be established. Biochemical tests chosen on grounds of suita¬ bility for screening large numbers of cases are not all-embracing and may fail to detect certain types of metabolic disturbance. Although the use of both clinical and biochemical screening will allow recognition of some clinical syndromes, it is likely that others cannot be characterized by current biochemical techniques. Our criterion for inclusion of patients in our study, namely the occurrence of mental sub- normality in siblings, was chosen with a view to selecting a population with a high risk of inherited metabolic defect. By requiring that patients shall satisfy this two-tier screening test, we hoped to obtain the maximal concentration of defects due to mutant genes. Since Pearson and Jaederholm (1914) drew attention to the probable existence of disorders of differing aetiology amongst persons of low intelligence, it has been shown that the latter fall into two broad groups. The first is the group of feeble-minded and educationally subnormal which represents the tail of the normal curve of the distribution of intelligence and in which the mode of origin is often multi-factorial and