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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    general discussion 75 abdominal or nervous systems. He has normal pre-pubertal genitalia. He had a normal chromosome complement. His E.E.G. showed atypical spike and wave activity. The fourth sibling (case 55) was born spon¬ taneously but prematurely after an otherwise normal pregnancy, weighing 2-25 kilo. Apart from a tendency to vomit in early infancy he made normal progress, sitting at 10 months, crawling at II and pulling up to stand at 12 months. Trembling similar to that of the other siblings was noticed in the 13th month. Examina¬ tion at that time showed no abnormality except for a coarse intention tremor. The I.Q,. (Griffiths Developmental Scale) was 85. Major epileptic attacks occurred from this time and continued with diminishing frequency until the age of 8 years. Progress ceased after the 12th month and his I.Q. at the ages of 2 and 12 was assessed as 56 and 25 respectively. His behaviour deteriorated, and he became hyperactive and destructive, but there has been no recent intellectual deterioration. Like his affected brothers and sister, he subsequently became cheerful and he now has a social maturity score that is high for his intelligence. He is continent, but has no speech. Apart from osteomyelitis (L. femur), which responded completely to treatment at the age of 4, he has had no serious illness. His height is 130-8 cm., which is at the 3rd percentile for normal children of his age. His weight is 28 • 5 kilo and his skull circumference is 53 ■ 3 cm. His hair and eye colouring are similar to those of his siblings, but his prog¬ nathism is more marked. No abnormality was detected in his cardiovascular, respiratory, gastrointestinal and nervous systems. His external genitalia are normal for his age. He has a normal chromosome complement. The E.E.G. showed frequent high voltage 3 cycles/ sec. delta rhythm, especially from posterior electrodes. Comments on family 2^ The clinical features of the four siblings have been so similar that there can be little doubt that they have the same condition. Thus, they made normal progress until 12 to 19 months after birth when signs of neurological involve¬ ment were noted. These were trembling, hyperkinesis and myoclonic spasms. In the second sibling (case 53) there was an episode of unexplained loss of use of one leg at the age of 7 months which preceded the onset of develop¬ mental arrest and other signs of neurological involvement by 5 and 12 months respectively. The third sibling (case 54) had severe gastro¬ enteritis followed by convulsions and a mild regression which may have been due to factors such as electrolyte imbalance unrelated to the ultimate disorder. Records of laboratory and other findings at this time are not available. However, since there is reliable evidence that subsequent progress was apparently normal, it seems unlikely that progressive deterioration commenced at this time. In all siblings, there¬ fore, it appears that the course of the disorder was rapidly progressive after the onset of first symptoms. Characteristically, developmental progress ceased abruptly and recently acquired skills were lost. After a short interval or at the same time neurological signs became manifest and they developed epilepsy (major, minor or myoclonic) and behaviour deterioration (especi¬ ally restlessness, uncontrollability and destruc- tiveness). These symptoms gradually subsided, there being no noticeable further intellectual deterioration. Fits ceased during childhood. Since there was no excess of hydroxyly.sine in the blood in any of the patients and no excessive rise in blood levels after oral loading in case 53, the biochemical findings may best be explained as a specific block in renal tubular reabsorption of free hydroxylysine in cases 52 and 53 and possibly of citrulline in case 52 (Benson et al., 1969). The urinary excretion of total hydroxylysine and hydroxyproline (i.e. including that present in the form of peptides) in all the affected siblings were within normal limits. Inheritance: compatible with autosomal recessive forms. (Case histories of patients in Groups A, В and С are given in the Appendix.) VI General Discussion In half of our families the affected siblings had similar physical or biochemical abnor¬ malities. The physical abnormalities were