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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    8 GENETIC STUDIES IN MENTAL SUBNORMALITY Table III Groupings of 141 families with idiopathic severe subnormality according to whether ordy males, only females or members of both sexes were known to have been affected Only males Both males and Only females Pedigree type of family affected females affected affected Total All affected in one sibship .... 28 26 12 66 All affected in one generation but in more than one sibship . . . . i 2 i 4 Affected in more than one generation.. 9 19 i 29 Information incomplete or not reliable 12 23 7 42 Total ...... 50 70 21 141 evidence suggestive of an X-linked explanation. Then, the families where males and females or females only were affected will be examined for indications on the pedigrees on the modes of inheritance. The evidence pointing to autosomal recessive inheritance from consanguinity and the clinical similarities between affected members in the same family will also be considered. Subsequently, the sibship data will be con¬ sidered to test two hypotheses. The association of males in sibships might be a simple conse¬ quence of the excess of male cases; and the reason for the male excess might be that much of the severe defect is determined by multi¬ factorial and threshold mechanisms, with males having a lower threshold than females. Pedigree evidence for X-linked recessive or sex-limited autosomal inheritance in those families with only males affected Severe subnormality in males is effectively a genetic lethal and so it is not possible to distin¬ guish between X-linked recessive and sex- limited autosomal dominant inheritance. For convenience in this paper, when X-linked recessive inheritance is mentioned it will always be with the proviso that sex-limited inheritance cannot be excluded. As will be seen from Table III, there were ten families where the information appeared to be as reliable as could be expected in investiga¬ tions of this kind, and where males only were affected in more than one sibship in the same or in different generations. These were families Nos. 41, 42, 59, 96, 103, 108, 161, 205, 228 and 248 (Fig. i). As will be seen from the pedigrees, all these families except No. 205 are compatible with X-linked inheritance. In family No. 161, however, V i also had con¬ sanguineous parents—the coefficient of in¬ breeding being о-0156. In addition to these families, in two others the pattern of distribution of males raised a suspicion of X-linked inheritance. In No. 216 all the males were sfeverely affected but one male had sisters who, although not severely subnormal, were certainly educationally subnormal. In family No. 40 the males were all severely subnormal, and were unable to speak and had limb spasticity, whereas the only affected female, II 2, though severely subnormal could speak and had no neurological signs. It is impossible to be more than speculative in formulating a genetic hypothesis for these families. Although they were not encountered in the survey it seems worth while to reproduce two pedigrees compatible with X-linked inheritance from two families referred for advice in 1970 as they lend support to an X-linked hypo¬ thesis (AS/655 CD/427). In the former family all affected members except II i, who is dead, have been seen. Only the propositus lived in the Oxford Regional Hospital Board area and he was only resident there after the end of the survey so that this family could not have been ascertained. Family CD/427, where