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.

    87/100 (page 73)
    FAMILIES WHERE SIBLINGS HAVE SIMILAR BIOCHEMICAL DISORDERS 73 who has two normal children, a normal brother aged 55, with one normal child and non- identical twin sisters (index cases ii and 12), aged 47. The parents were normal and un¬ related. Their four siblings and parents are normal. I.Q.s are 30 and 39. Their behaviour is quiet and co-operative. Skull circumferences are 46 • 9 cm. ; the foreheads are prominent and accentuated by a high frontal hairline. Their noses, orbits and ears are asymmetrical, and the ears abnormally large and unrolled with fused lobes, showing greater malformation on the smaller (right) side. Both sisters show asymmetry of diameter and length of the arms and legs, the right being smaller than the left. No other physical abnormality has been found. E.E.G.s show spike and wave activity, though there is no known epilepsy. The only biochemical abnormality noted was a persistently high urinary excretion of j8-alanine, 1350-1280 /xmol/24 hours (normal; none or a trace). No j8-alanine was detected in the blood of the patients or controls. These data are compatible with the presence of a specific defect in the renal tubular reabsorption of j8-alanine, which is being investigated further. The biochemical disorder differs from that in the boy described by Scriver et al. (1966), since in the latter there was hyper-^-alaninaemia. Inheritance : compatible with autosomal recessive form. Family 7—i-methylhistidinuria The sibship consisted of non-identical twin brothers who died at two weeks of age, three sisters of normal intelligence and the two affected brothers (index cases 15 and 16) who are non-identical twins aged 30 years. The parents are apparently normal. Gestation was about 36 weeks but there was no other recorded abnormality in the perinatal period. The time of onset of mental retardation is not known but was probably in early childhood. Both have psy¬ chotic features. Their I.Q,.s are 50 and 59, but no other abnormalities were detected. The only biochemical abnormality was a persistently high urinary excretion of i-methyl- histidine (260-290 jU,mol/ 24 hours; normal, mean 77-2, S.D. 54*4 ju.mol/24 hours). Since there was no increase of plasma i-methylhisti- dine the data are compatible with a specific defect of renal tubular reabsorption of i-methyl- histidine. Investigation of these patients is still in progress. Inheritance: compatible with autosomal recessive or X-linked form. Family 25—Hyperkinesis, trembling attacks, myoclonic spasms, epilepsy and hydroxylysinuria The sibship consists of 3 affected boys, aged 18, 14 and 12 (index cases 52, 54 and 55), an affected sister aged 15 (index case 53) and a normal sister aged 6. The parents are unrelated, the father English and the mother Irish by birth. Apart from the son of a maternal great-aunt who has mental deficiency of undetermined cause, there is no other instance of subnormality in the family. Of the parents' four married siblings there has been only one offspring, a normal boy. Both parents were aged 21 when the eldest affected child was born in 1950. The eldest sibling (case 52) was born spon¬ taneously after a normal pregnancy of 39 weeks, weighing 3-2 kilo. Transient neonatal jaundice of unknown severity occurred, but progress was considered normal for the first few months, as he sat at six months, stood with support at 16 months and began to say single words at 15-16 months. After a febrile illness lasting two weeks, diagnosed first as poliomyelitis and later, on account of a rash, as measles, there appeared trembling, hyperkinesis, myoclonic jerks and major convulsions. Speech already attained was lost and no further progress was made. He became restless, uncontrollable and destructive. Investigations at this time (National Hospital, Queen Square) revealed no abnormality. Since the age of three he has become quieter and there has been no apparent further deteriora¬ tion since early childhood. His height, 152-4 cm. and weight, 40-3 kilo are both below the 3rd percentile ( - 3 S.D.) for normal children of his age. His skull circum¬ ference is 53 • 3 cm. He is cheerful and continent. Though he understands simple orders he has no speech. His I.Q_. is 40. He has brown hair and blue eyes and looks younger than his age. No abnormality was detected in his cardio-