Intellectual Functioning in Tu r n e r Sy n d ro m e Specific abnormalities of perceptual organization occur in individuals with Turner This association between chromosomal endowment and cognition provides a unique opportunity to study the inheritance of intellectual skills.

The chromosomal defect in Turner syndrome results in the functional absence of genetic information contained on the short arm of one of the x sex chromosomes. At least 50 per cent of individuals with Turner syndrome lack a second x chromosome7* *and theremainder have any one of a variety of abnormal chromosomal patterns (e .g . 46Xxp-, 46xringx, 4 5 ~ 0 / 4 6 x x , 45~0/46xY) . The phenotype may vary from minimal alteration of physical appearance to any combination of the classic Turner stigmata. These include webbing of the neck, short stature, skeletal abnormalities, pigmented moles, coarctation of the aorta, shield chest and facial hypoplasia.

Many reports of Turner syndrome have included mental retardation as a clinical

featureY-". Defective intellectual func- tioning has been associated with neck webbing", I * , the 45x0 karotype'' and mosaicism14~ 15.

In a selected uncontrolled study of 37 patients with Turner syndrome, MONEY16 demonstrated a normal distribution of Full-scale IQ scores. These patients had intact Verbal IQ scores and a normally distributed but decreased set of scores on the Performance IQ subtests. In another analysis of intelligence-test scores of vr z Turner individuals, GARRON and col- m leagues'' attributed the lowering of Full- scale IQ to the results of specific subtests

intellectual impairment. 2 GARRON4 provided evidence that mental B

retardation is not a feature of Turner 2 syndrome by investigating all identifiable cases in the Chicago area and comparing s 2

3 their performance on intelligence tests with paired control subjects, matched for over- all Wechsler intelligence scores, race, Qi

3 educational level, residence and social % class. He found no increased incidence of

either severe or moderate mental retar- dation among the group with Turner E

E syndrome. There was no correlation between intellectual level and either a

karyotype or somatic stigmata. 6

descriptive labels t o perceptual deficits,

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Investigators have attached many 539

but the terms often reflect the type of psychological test employed or theories concerning intellectual functioning in vogue at the time of the study. SHAFFER’ described the deficit occuring in Turner syndrome as a disorder of perceptual organization and spatial ability. These terms were refined by ALEXANDER and colleagues** who delineated three consistent cognitive defects. These were a spatial orientation deficit, a directional sense disorder limited to extracorporeal space, and a mild numerical disability. Poor memory recall and attention span were also noted’’.

SILBERT and colleagues5 used a complex five-hour battery of tests designed to subdivide perceptual disorders into more specific areas. They applied a new vocabulary to the perceptual deficits in Turner syndrome and implicated the existence of aberrant ‘mental operations’. They demonstrated a Turner syndrome- related deficiency in visualizing spatial configuration from memory and in appropriately combining component parts of an object. Difficulties with temporal and auditory sequencing, both tasks involving memory skills, were also noted. The Turner subjects performed as well as the controls on tasks requiring the breaking down of patterns into their component parts. N o numerical disability was observed.

WABER~’ administered neuropsycho- logical tests to individuals with Turner syndrome in an effort to clarify the nature of a ‘processing’ disorder and to establish whether there was a localized area of cerebral dysfunction. She did not demonstrate a specific deficit in spatial ability or perceptual organization. She postulated that these unexpected findings could be accounted for by dysfunction of underlying processes required for the completion of previously administered tests of spatial ability. At fault are co- ordination and memory, visual and possibly auditory. Tests such as the Benton Visual Retention, Bender Gestalt or the Draw-a-Person rely on these processes and yield abnormal results when used for subjects with Turner syndrome. Results of tests of ‘spatial’ ability that do not rely on these processes, such as the Block Design subtest of the Wechsler Intelligence Scale, 540

the California Test of Mental Rotations or the Raven Progressive Matrices are relatively unaffected.

ROVET and N U T L E Y ~ examined the manner in which Turner subjects solve spatial orientation problems by giving a test of mental rotation to 31 Turner subjects and controls, matched for age and verbal IQ scores. They found that although those with Turner syndrome did not perform as well as the controls, they used a similar rotation strategy in solving the tasks.

The search for an anatomical locus of cerebral pathology in perceptual disorders, and the assignment of a specific function to a cortical area, has generated much interest and many theories, but no answers. ALEXANDER and implicated the parietal lobe as the seat of problems with spatial ability in those with Turner syndrome. KOLB and H E A T O ~ I ~ ~ and SILBERT and colleagues5 favored the right cerebral hemisphere. In 1979, WABER” presented data that supported the occurrence of a non-localized disorder in Turner syndrome involving the parietal and frontal lobes of both hemispheres. This position is consistent with the theory that early alteration in brain development, presumably due to the genetic influence of an abnormal chromosomal pattern, produces a generalized effect on brain function later in lifez3.

Such an alteration of brain function was postulated by NETLEY24, who suggested that sex hormones are necessary for lateralization of language functions to the left hemisphere. The presence of left-ear dominance, and hence theoretical right- hemisphere localization of verbal func- tions, in subjects with Turner syndrome in dichotic listening tasks, in which different digit triads are presented to the right and left ears simultaneously,sug estsabnormal hemispheric speciali~ation’~* 2 5 . Further- more, it has been suggested that language function abnormally processed in the right hemisphere somehow interferes with non- verbal tasks which are normally analyzed in this area2’.

It is interestingthat reading skills are not adversely affected in Turner syndrome26. This suggests that the perception of the shape and directional orientation of letters is related to a separate cognitive process

from the one found t o be defective in this syndrome. A child with a specific reading disability belongs to a distinctly different group of perceptual disorders that deal with the broad area of spatial orientation.

The test performance profile observed in Turner subjects is not typical of either males o r females. These individuals have depressed performance in areas in which males excel, such as spatial and numerical

as well as in skills in which females usually excel, such as word fluency and rapid automatizednaming2’. Although individuals with Turner syndrome are phenotypically and emotionally female32* 33 ,

they perform intellectually in a manner consistent with their indeterminate sex- chromosome status. Those with Turner syndrome mosaicism who have the Y chromosome, such as 4 5 X o / 4 6 x u , have been noted to exhibit a female attern on tests of spatial orientation , which suggests that the presence of the Y chromosome at an early gestational stage does not exert an important influence on the eventual development of perceptual skills.

Experimental studies on laboratory animals indicate that gonadal hormones play a critical r61e in the normal maturation of brain function in many mammalian species3’. Individuals with

P4

References I . Shaffer, J. W. (1962) ‘A specific cognitive deficit

observed in gonadal aplasia (Turner’s syn- drome).’ Journal of Clinical Psychology, 18,

2. Alexander, D., Walker, H. T., Money, J . (1964) ‘Studies in direction sense. I: Turner’s syndrome.’ Archives of General Psychiatry, 10, 337-339.

3. Bekker, F. J. (1969) Dwerggroei en Sexueel Infanrilisme. (Aspects of Psychic Development in Children with Retarded Somatic Devel- opment.) Leiden: €1. E. Stenfert Kroese.

4. Garron, D. C. (1977) ‘Intelligence among persons with Turner’s syndrome.’ Behavior Genetics, 7 , 105-127.

5 . Silbert, A. R., Wolff, P. H., Lilienthal, J. (1977) ‘Spatial and temporal processing in patients with Turner syndrome.’ Behavior Genetics, 7 , 11-21,

6. Rovet, J . , Nutley, C. (1980) ‘The mental rotation task performance ofTurner syndrome su bjects.’ Behavior Genetics. 10, 437-443.

7. Federman, D. D. (1967) Abnormal Sexual Development. Philadelphia: W. B. Saunders.

8. Polani, P. E. (1969) ‘Chromosome phenotypes- sex chromosomes.’ I n Fraser, F. C., McKusick, V. A. (Eds.) Proceedings of the 3rdInternational Congress on Congenital Malformations. Excerpta Medica International Congress Series no. 204. Amsterdam: Excerpta Medica.

403-406.

Turner syndrome are unable to produce gonadal hormones throughout postnatal development, and consequently are physically immature. By analogy, im- mature cognitive functioning may also result from a lack of neurohormonal influence on the brain. This hypothesis is supported by WABER’S observation that prepubertal girls and subjects with Turner syndrome score similarly on psychological tests2’. Electrophysiological data were reported by Buchsbaum et al. 3 6 , who noted that averaged visual evoked responses in adults with Turner syndrome most closely resembled patterns seen in female children between six and nine years of age.

The existence of Turner syndrome provides an opportunity to study genetic determinants of cognitive skills. Further studies using new electrophysiological methods, including computer-aided analysis of cortical electrical activity37, may provide the next step in the investigation of human intelligence.

FRANK S. PIDCOCK

Department of Pediatrics, Jeflerson Medical College, Thomas Jefferson University, Philadelphia, Pa. 19107.

9. Haddad, H. M., Wilkins, L. (1959) ‘Congenital anomalies associated with gonadal aplasia: review of 5 5 cases.’ Pediatrics. 23, 885-902.

10. Polani, P. E. (1960) ‘Chromosomal factors in certain types of educational subnormality.’ In Bowman, P. W., Mautner, H. B. (Eds.) Mental Retardation. New York: Grune & Stratton.

11. Van Gemund, J. J., Van Geldern, H. H. (1961) ‘Gonadal dysgenesie bij kinderen.’ Nederlands Tijdschrift voor Geneeskunde. 105, 1678-1683.

12. Bishop, P. M. F., Lessof, M. H., Polani, P. E. (1960) ‘Turner’s syndrome and allied con- ditions.’ I n Austin, C. R. (Ed.) Sex Differentiation and Development. Cambridge: Cambridge University Press.

13. Lindsten, J. (1963) The Nature and Origin of X Chromosome Aberrations in Turner’s syndrome. Stockholm: Almquist and Wiksell.

14. Leao, J. C., Voorhess, M. L., Schlegel, R. J., Gardner, L. I. (1966) ‘XX/XO mosaicism in nine preadolescent girls: short stature as a presenting complaint.’ Pediatrics. 38, 972-98 I .

1 5 . Goldberg, M. B., Scully, A. L., Soloman, I . L., Steinbach, H. L. (1968) ‘Gonada! dysgenesis in phenotypic female subjects. American Journal of Medicine, 45, 529-543.

16. Money, J . (1963) ‘Cytogenetic and psychosexual incongruities, with a note on space-form blindness.’ American Journal of Psychiatry,

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Lindsten, J. (1973) ‘An explanation of the apparently increased incidence of moderate mental retardation in Turner’s syndrome.’ Behavior Genetics, 3, 37-43.

18. Alexander, D., Money. J. (1966) ‘Turner’s syndrome a n d Gerstman’s syndrome: neur- ophysiologic comparisons.’ Neuropsychologia, 4, 265-273.

19. Money, J . , Alexander, D. (1966) ‘Turner’s syndrome: further demonstrations of thy presence of specific cognitional deficiencies. Journal of Medical Genetics. 3, 4 7 4 8 .

20. Waber, D . P. (1979) ‘Neurophysiological aspects of Turner’s syndrome.’ Developmental Medicine and Child Neurology. 21, 58-70.

21. Money, J . (1973)‘Turner’s syndrome and parietal lobe functions.’ Cortex, 9, 385-393.

22. Kolb, J . E.. Heaton, R . K . (1975) ‘Lateralized neurologic deficits and psychopathology in a Turner syndrome patient.’ Archives of General Psychiatry, 32, I 198- 1200.

23. Luria, A. R. (1973) The Working Brain (Trans. B. Haigh). New York: Basic Books.

24. Netley, C. (1976) ‘Dichrotic listening of callosal agenesis and Turner’s syndrome patients.’ In Segalowicz, S. J., Gruber , F. A. (Eds.)Languuge Development and Neurological Theory. New York: Academic Press.

25. Netley, C., Rovet, J. (1982)‘Atypical hemispheric Iateraliiation in Turner syndrome su6jects., Cortex. 18, 377-3x4.

26. Alexander, D., Money, J. (1965) ‘Reading ability, object constancy and Turner’s syn- drome.’ Perceptual and Motor Skills. 20, 981-984.

27. Anastasi, A. ( 1958) Differential Psychology: Individual and Group Differences in Behavior. New York: Macmillan.

28. Maccoby, E. E. (1966) ‘Sex differences in intellectual functioning.’ In Maccoby, E. E . (Ed.) The Development of Sex Differences. Palo Alto: Stanford University Press.

To What Extent Does Food Sensitivity Contribute to Headache Recurrence? The hypothesis that foods can influence headache propensity has been discussed for thousands of years’. In the past decade, The Lancet, with its provocative papers, cogent leaders (unsigned editorials) and relatively large ‘Letters to the Editor’ section, has served as a forum for a discussion of migraine and allergy, as well

29. MacFarlane-Smith. I . (1964) Spatial Abilify: Its Educational and Social Signijicance. London: University of London Press.

30. Tyler. L. E. (1965) The Ps.vcho1og.v of Human DiJferences. 3rd Edn. New York: Appleton- Century-Crofts.

31. Werdelin, I . (1961) Geometrical Ability and the Space Factors in Boy> and Girls. h n d , Sweden: University of Lund Press.

32. Hampson, J. L., Hampson, J. G.. Money, J. (1955) ‘The syndrome of gonadal agenesis (ovarian agenesis) and male chromosomal Dattern in eirls a n d women: Dsvcholoeical studies.‘ Buli t in of the Johns Ifopkitk I l o s ~ t a l ,

33. Shaffer, J . W . (1963) ‘Masculinity-femininity 97. 207-226.

a n d other personality traits in gonadal aplasia.’ In Beigel, H . (Ed.) Advances in Sex Research. New York: Hoeber.

34. Ebbin, A. J . , Howell, V. V., Wilson, M. G. (1980) ‘Deficits in space-form perception in patients with sex chromosome mosaicism (45,X/46,XY).’ Developmental Medicine and Child Neurology, 22, 352-361.

35. McEwan, B., Denef. C. J . , Gerlach, J . I.., Plapinger, L. (1974) ‘Chemical studies of the brain as a steroid hormone target tissue.’ I n Schmitt , F. 0.. Worden, F. G. (Eds.) The Neurosciences. Third Studv Program. Cambridge, Mass.: M I T Press.

36. Buchsbaum, M., Henkin, R. I . , Christiansen, R. I . (1974) ‘Age and sex differences in averaged evoked responses in a normal population, with observations o n patients with gonadal dys- genesis.’ Electroencephalography and Clinical Neurophysiology. 31, 137- 144.

37. John , E. R., Karmel, B. Z.. Corning, W. C., Easton, P. , Brown, D., Ahn. H . , J o h n , M., Harmony, T., Prichep. A, , Toro, A,, Gerson, I . , Bartlett, F.. Thatcher, R.. Kaye, H.. Valdes. P.. Schwartz. E . (1977) ‘Neurometrics.’ Science. 196, 1393-1410.

as migraine and food or beverage Three of the more recent

discussions have been prompted by a report linking migraine to allergy-some of the letters and articles that followed raised doubts about definitions and

. This emphasis on methodological issues appears to reflect readers’ concern about the lack of reproducibility that characterizes this area of study. Other letters raised doubts about the generalizability of the reported findings20325, and again the concern appears to be with inconsistencies.

Recent reports suggest that allergy contributes minimally to headache recur- rence26*27. Other recent studies indicate that non-allergic food sensitivities do increase the probability of a headache in

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