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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    бз genetic studies in mental subnormality inheritance polygenic (Fraser Roberts, 1952). In the second group are the severely subnormal patients, and it is here that inheritance is more likely to depend on single gene defects. The group comprises numerous and diverse disorders ; some of them have a genetic origin, and of those that do many are the expression of homozygous abnormal autosomal recessive genes (Fraser Roberts, 1950). Among this group of low grade patients the forms of mental subnormality caused by meta¬ bolic disorders may be expected to occur with greatest frequency and we have, therefore, used low intelligence as a major criterion for selection. Clear separation of the two groups on the basis of I.Q., however, is not possible. Fraser Roberts has shown that there is considerable overlap in the range of I.Q,.s between 40 and 60, and it has been established that in certain types of inborn errors of metabolism, intelligence may be within the normal range in a high proportion of cases. It is possible, therefore, that some subjects with these types of disorders may be excluded when low I.Q,. is employed as a selection criterion. Thus, in one study of homocystinuria (which is probably the second most common inherited metabolic error asso¬ ciated with mental subnormality) intelligence was assessed as normal in 16 out of 38 subjects (Schimke et al., 1965). Parents and unaffected siblings were not studied at this stage because data from the hospital case records were incomplete. Procedure for selection and investigation All the subjects were in-patients at Leybourne Grange Hospital, a 1,400 bed hospital for sub¬ normal and severely subnormal children and adults. The criteria for selection based on hospital records were that the patients should have: (i) an I.Q.. of 50 or less, and (2) a full sibling with an I.Q. of 60 or less. Sixty-six patients from 30 famihes met these requirements and have been investigated as described below. II The Procedure of the Investigation Family and Personal History Data have been obtained from hospital records, from the local health authority's medical and welfare records; and in the majority of families, a further history has been obtained by interview with the relatives. Clinical examination and psychological assess¬ ment of unaffected relatives were not under¬ taken. Physical assessment All patients were examined clinically (by P.N.S.). When this examination revealed anomalies or the existence of anomalies common to other members of a sibship, the significance of the findings was assessed in conference. Radiological and cytogenetic investigations and audiometry were performed as necessary when indicated on clinical grounds. Height and weight measurements of all patients were compared with the normal figures for the general population (Tanner et al., 1966), and allowance was made for the fact that the mean figures for subnormal patients are below those of the general population. As the sub¬ normal populations for which figures have been published are not strictly comparable to those for the present survey, we considered comparison with normal means to be less open to criticism. Accordingly, patients have been considered to be abnormally retarded in growth when their height was less than the normal mean by 3-5 standard deviations (S.D.) or more. Genetic classification The occurrence of mental subnormality of unknown cause in siblings is in itself sufficient reason to justify a suspicion of genetic disorder. In a number of our families data were insufficient for any more definite conclusion. When one of the parents was mentally retarded, a dominant form of inheritance was considered but could not be confirmed, since relatives were not available for investigation. Autosomal recessive form of inheritance was consistent with the genetic data of the majority of our families, but was asserted with greater confidence in families (a) when there was parental consanguinity and (b) in families in which the afifected siblings had an identical metabolic abnormality which was not present in their parents and in which X-linked inheri-