The YY Syndrome

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583 selves for study by the technique of differential blood- sampling devised by BUTTERFIELD and his colleagues extend well beyond the boundaries of endocrinology. The YY Syndrome THIS title seems the most suitable (though so far as we know it has not been used before) for the new and very interesting syndrome of sex-chromosome abnormality described from Edinburgh on p. 565. The sex chromo- somes have been very extensively studied, and once XO, XXY, and XXX had been described in 1959, it seemed the main ground had been covered, for the innumerable variants involving mosaics and structural variations, especially in Turner’s syndrome,! seemed all to be related to these basic patterns. But by last year it had become clear that XX/XY mosaics, with their extra- ordinary origin in double fertilisation, made a fourth entity, even if rather a rare one.2 Now it seems there is a fifth. It is new only in being recognised as a syndrome, for at least 14 examples of XYY and 1 of XYYY cases have been reported and at least 8 XXYY 4 and 1 XXXYY.5 To those who described these patients, they seemed to present no very consistent picture. The XXYY cases undoubtedly had all the features of XXY Klinefelter’s syndrome; the XYY cases mostly had mild mental defect, and a variety of other congenital defects; but, since chromosome examinations are generally done only on people with some such abnormality, this meant very little. It is not therefore surprising that it has been generally believed that the second Y has no specific effect-the more so that the first patient described6was of average intelligence and fertile. There had, however, been a suggestion of an effect on stature.4 4 The basic difficulty was that there was no easy way of collecting a series of cases, for the sex chromatin, which depends only on the number of X chromosomes present, was of no avail. COURT BROWN noted in 1962 that delinquency seemed to be high among his own patients with various sex- chromosome anomalies. 7 There has been no general confirmation of this, but a Sheffield group 8 acted on the hint and looked for sex-chromosome anomalies in special security institutions for mentally abnormal patients liable to criminal behaviour. There had already been some suggestion that chromatin-positive males were especially common among such patients.9 CASEY et a1. 8 confirmed this, finding among 942 males 21 who were chromatin-positive (2-2%, or twice the number among ordinary mental defectives, and ten times that in a normal population). But much more interesting are the chromosome findings in these 21 patients: 12 were XXY, 1. Lancet, 1965, ii, 529. 2. ibid. 1965, i, 1052. 3. Townes, P., Ziegler, N. A., Lenhard, L. W. ibid. p. 1041. 4. Barr, M. L., Carr, D. H., Soltan, H. C., Wiens, R. G., Plunkett, E. R. Can. med. Ass. J. 1964, 90, 575. 5. Bray, P., Josephine, A. J. Am. med. Ass. 1963, 184, 179. 6. Sandberg, A. A., Koepf, G. F., Ishihara, T., Hauschka, T. S. Lancet, 1961, ii, 488. 7. Court Brown, W. M. ibid. 1962, ii, 508. 8. Casey, M. D., Segall, L. J., Street, D. R. K., Blank, C. E. Nature, Lond. 1966, 209, 64. 9. Forssman, H., Hambert, G. Lancet, 1962, i, 1327. 2 XXX/XY, and no less than 7 were XXYY. By contrast, in most series, less than 1 in 10 of chromatin-positive cases are XXYY. Since the excess of chromatin-positive cases in these institutions could be almost wholly accounted for by the XXYY cases, it seemed likely that such patients had a special tendency to delinquent behaviour. They were also unusually tall. Since in other respects these patients had the features of ordinary XXY Klinefelter’s syndrome, it could be deduced that the delinquency and extra height were not a characteristic of the whole XXYY grouping, but of the extra Y alone. If that were so, delinquency and height without Klinefelter’s syndrome should also be character- istic of XYY cases. On this assumption, the Edinburgh group used their now considerable resources to make chromosome counts on all available male patients in a Scottish special-security institution. JACOBS et all had already reported finding 7 XYY cases and 1 XXYY in the first 197 examined. There were also 1 XXY/XY mosaic and 3 with various autosome anomalies, which is very much the usual run of things among mental defectives; but the YY cases are astonishingly frequent: the Edinburgh group have seen only 1 XYY case among 2000 male chromosome counts that could be regarded as controls. Like the Sheffield XXYY cases, they were often unusually tall, but they bore no evidence of Klinefelter’s syndrome. Dr. PRICE and his colleagues (p. 565) now bring the Carstairs tally to 9 cases out of 315 patients, and describe the clinical findings. No new diagnostic features emerge. 8 of the 9 are high-grade mental defectives. Their type of delinquency was not clearly different from that of other patients in the hospital, though most were aggressive and violent. Physically there seemed nothing at all remarkable about them except their height: 6 of the 9 were over 1-8 metres (6 ft.). The height is so striking a feature that it has been said that half of all men over 6 feet in special-security institutions are YY-probably an exaggeration, but unlikely to be a very gross one. The recognised mental disorders associated with chromosome anomalies have so far been confined to the largely non-specific mental defect present in varying degree with most of the major anomalies. Here we seem to have a fairly specific mental disorder associated with a highly specific lesion-a matter of considerable psychiatric importance. XYY must make its small but significant contribution to the country’s delinquent population. Chromosomologically, the condition is of immense interest. Until human XO and XXY were described, the mammalian Y was believed to be an inert marker. Thereafter it was believed to carry only its single major testis-evoking gene. But besides the Indian hairy-ears gene that is definitely locatable on the Y, evidence from some of the Turner’s syndrome variants tends increasingly to indicate that there is a paired segment common to X and Y that carries important genetic materia1.1 The somatic anomalies of Turner’s syndrome are believed to be due to monosomy 10. Jacobs, P. A., Brunton, M., Melville, M. M., Brittain, R. P., McClemont, W. F. Nature, Land. 1965, 208, 1350.

Transcript of The YY Syndrome

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selves for study by the technique of differential blood-sampling devised by BUTTERFIELD and his colleaguesextend well beyond the boundaries of endocrinology.

The YY SyndromeTHIS title seems the most suitable (though so far as we

know it has not been used before) for the new and veryinteresting syndrome of sex-chromosome abnormalitydescribed from Edinburgh on p. 565. The sex chromo-somes have been very extensively studied, and once XO,XXY, and XXX had been described in 1959, it seemedthe main ground had been covered, for the innumerablevariants involving mosaics and structural variations,especially in Turner’s syndrome,! seemed all to berelated to these basic patterns. But by last year it hadbecome clear that XX/XY mosaics, with their extra-ordinary origin in double fertilisation, made a fourthentity, even if rather a rare one.2 Now it seems there is afifth. It is new only in being recognised as a syndrome,for at least 14 examples of XYY and 1 of XYYY caseshave been reported and at least 8 XXYY 4 and 1XXXYY.5 To those who described these patients, theyseemed to present no very consistent picture. TheXXYY cases undoubtedly had all the features of XXYKlinefelter’s syndrome; the XYY cases mostly had mildmental defect, and a variety of other congenital defects;but, since chromosome examinations are generally doneonly on people with some such abnormality, this meantvery little. It is not therefore surprising that it has beengenerally believed that the second Y has no specificeffect-the more so that the first patient described6wasof average intelligence and fertile. There had, however,been a suggestion of an effect on stature.4 4 The basic

difficulty was that there was no easy way of collecting aseries of cases, for the sex chromatin, which dependsonly on the number of X chromosomes present, was ofno avail.COURT BROWN noted in 1962 that delinquency seemed

to be high among his own patients with various sex-chromosome anomalies. 7 There has been no generalconfirmation of this, but a Sheffield group 8 acted on thehint and looked for sex-chromosome anomalies in specialsecurity institutions for mentally abnormal patientsliable to criminal behaviour. There had already beensome suggestion that chromatin-positive males wereespecially common among such patients.9 CASEY et a1. 8confirmed this, finding among 942 males 21 who werechromatin-positive (2-2%, or twice the number amongordinary mental defectives, and ten times that in anormal population). But much more interesting are thechromosome findings in these 21 patients: 12 were XXY,1. Lancet, 1965, ii, 529.2. ibid. 1965, i, 1052.3. Townes, P., Ziegler, N. A., Lenhard, L. W. ibid. p. 1041.4. Barr, M. L., Carr, D. H., Soltan, H. C., Wiens, R. G., Plunkett, E. R.

Can. med. Ass. J. 1964, 90, 575.5. Bray, P., Josephine, A. J. Am. med. Ass. 1963, 184, 179.6. Sandberg, A. A., Koepf, G. F., Ishihara, T., Hauschka, T. S. Lancet,

1961, ii, 488.7. Court Brown, W. M. ibid. 1962, ii, 508.8. Casey, M. D., Segall, L. J., Street, D. R. K., Blank, C. E. Nature, Lond.

1966, 209, 64.9. Forssman, H., Hambert, G. Lancet, 1962, i, 1327.

2 XXX/XY, and no less than 7 were XXYY. By contrast,in most series, less than 1 in 10 of chromatin-positivecases are XXYY. Since the excess of chromatin-positivecases in these institutions could be almost whollyaccounted for by the XXYY cases, it seemed likely thatsuch patients had a special tendency to delinquentbehaviour. They were also unusually tall.

Since in other respects these patients had the featuresof ordinary XXY Klinefelter’s syndrome, it could bededuced that the delinquency and extra height were nota characteristic of the whole XXYY grouping, but of theextra Y alone. If that were so, delinquency and heightwithout Klinefelter’s syndrome should also be character-istic of XYY cases. On this assumption, the Edinburghgroup used their now considerable resources to makechromosome counts on all available male patients in aScottish special-security institution. JACOBS et all hadalready reported finding 7 XYY cases and 1 XXYY inthe first 197 examined. There were also 1 XXY/XYmosaic and 3 with various autosome anomalies,which is very much the usual run of things amongmental defectives; but the YY cases are astonishinglyfrequent: the Edinburgh group have seen only 1 XYYcase among 2000 male chromosome counts thatcould be regarded as controls. Like the SheffieldXXYY cases, they were often unusually tall, but

they bore no evidence of Klinefelter’s syndrome.Dr. PRICE and his colleagues (p. 565) now bring theCarstairs tally to 9 cases out of 315 patients, and describethe clinical findings. No new diagnostic features emerge.8 of the 9 are high-grade mental defectives. Their typeof delinquency was not clearly different from that ofother patients in the hospital, though most were

aggressive and violent. Physically there seemed nothingat all remarkable about them except their height: 6 of the9 were over 1-8 metres (6 ft.). The height is so strikinga feature that it has been said that half of all men over6 feet in special-security institutions are YY-probablyan exaggeration, but unlikely to be a very gross one.The recognised mental disorders associated with

chromosome anomalies have so far been confined to the

largely non-specific mental defect present in varyingdegree with most of the major anomalies. Here we seemto have a fairly specific mental disorder associated witha highly specific lesion-a matter of considerable

psychiatric importance. XYY must make its small butsignificant contribution to the country’s delinquentpopulation. Chromosomologically, the condition is ofimmense interest. Until human XO and XXY were

described, the mammalian Y was believed to be aninert marker. Thereafter it was believed to carry onlyits single major testis-evoking gene. But besides theIndian hairy-ears gene that is definitely locatable on theY, evidence from some of the Turner’s syndromevariants tends increasingly to indicate that there is a

paired segment common to X and Y that carries

important genetic materia1.1 The somatic anomalies ofTurner’s syndrome are believed to be due to monosomy10. Jacobs, P. A., Brunton, M., Melville, M. M., Brittain, R. P., McClemont,

W. F. Nature, Land. 1965, 208, 1350.

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of this segment: one can perhaps regard the YY syn-drome as the effect of trisomy of the same segment, andthus a kind of counterpart of Turner’s syndrome.One must assume, since there is no suggestion yet ofabnormal height or delinquency in XXX females (andCASEY et al. give some figures relevant to this), thatX-inactivation prevents manifestation of the syndromein X-trisomy.

If we cared to refer to the YY syndrome as " anti-

Turner’s " (not that we think there is much profit indoing so), we could bring it into line with another

possible new syndrome-so-called "

anti-mongolism "

due to deletion of part of chromosome 21."" With

LEJEUNE and PENROSE both supporting it, anti-mongolismhas formidable claims to recognition as a distinct entity.Cri-du-chat also has its counterpart, with trisomy of thatsegment of chromosome 5 which is deleted in cri-du-chat proper.14 All such monosomy-trisomy pairs are ofinterest, but not too much should be made of thesuggestion of oppositeness implicit in the " anti- "nomenclature: it is slight enough in anti-mongolismitself and non-existent with the cri-du-chat pair. Yet itis worth noting that a height under 5 feet is the mostconstant somatic feature of Turner’s syndrome, and oneover 6 feet equally characteristic of the YY syndrome.

Annotations

SONNE IN SCHOOLS

THE latrines in some of our schools are lamentable.Earth-closets are not extinct, and water-closets may beroofless, cold, damp, and spider-ridden. They were oftenbuilt at the distal end of the playground-maybe foreasier connection to the drains or for fear of the smell inthe days before the drains were there (the miasmatictheory of disease is not yet dead). Our forebears put firstthings first. A school was to be a waterproof and reason-ably warm building where the three Rs were to be taught.Children’s bowels and bladders had to be emptied, andplaces for doing so were provided in accordance with thepractice of the age (and they were probably far betterthan those the children had at home). For many yearseducation authorities have been doing their best to

modernise these places to the standards of today, but it isnot easy. The Victorians built well, but seldom with anythought of extension or improvement, and renovationhas become a costly business. If the choice lies between anew lavatory and a new library the vote goes to thelibrary. The council of the British Ceramic SanitarywareManufacturers takes a contrary view. In a new pamphlet 15it makes much ado about the dangers to health inherentin these old latrines. One of the arguments is based on theincrease in Sonne dysentery in the past twenty years; butthis would be more impressive if the increase did notcoincide with the building of many new schools fitted withevery modern sanitary convenience and with strenuous11. Lejeune, J., et al. C.r. Acad. Sci., Paris, 1964, 259, 4187.12. Reisman, L. E., Kasahara, S., Chung, C.-Y., Darnell, A., Hall, B.

Lancet, Feb. 19, 1966, p. 394.13. Penrose, L. S. ibid. p. 497.14. ibid. 1965, i, 35. 15. Survey on Sanitation in Primary Schools. Council of British Ceramic

Sanitaryware Manufacturers.

efforts everywhere to replace the old latrines by some-thing better.

Sonne dysentery today is a disease of dukes and dust-men-or rather of their children. In a school it is not somuch a medical disaster as a social nuisance. No childwill die and few will be seriously ill, but a school with two-thirds of its pupils missing is hardly a school. Some ofthose absent will have Sonne dysentery, and some willhave been kept at home-in case. It is reasonable tobelieve that the organism gets into circulation on fingerscontaminated at the anus and perhaps by aerosols createdby the flush of the water-closet (is this a good mark for theearth closet ?). Hutchinson 16 showed that during an

epidemic the organism could be recovered from the

lavatory seats, the handles on the chains, and most otherparts of the school water-closets. The children are told towash their hands after they have emptied their bowels; butsome schools are poorly supplied with wash-basins, andit may be that nothing short of a " surgical scrub " isenough. The addition of a disinfectant to the wash waterhas been tried, but without very obvious success. Chemo-prophylaxis has been no more effective so far.

In a school epidemic of Sonne in Worcester the problemwas attacked more deliberately and thoroughly than is

usual, and a full account 17 of the methods used shouldencourage others to repeat them. There were 192 pupilsin the school. On the first day of the outbreak 7 wereabsent; on the ninth 67; and thereafter the epidemicdeclined. A regimen to control infection was begun on thesixth day. Bowls containing benzalkonium chloride

(1000 p.p.m.) were put in every classroom. Each childhad to submerge his hands in this solution while he countedten when he arrived in the morning, before the mid-morning milk and before dinner, and when he left forhome. The drill was repeated each time the child returnedfrom the lavatory. In addition to this personal hygiene,the caretaker made a round every two hours wiping doorhandles, lavatory seats, and taps with " white fluid".It all took a long time, but the lesson in personal hygienewas thought to justify some interference with thecurriculum.

The number of absent pupils began to decline on thetenth day of the outbreak (i.e., four days after the pre-ventive measures were instituted). Ten days later theywere all back at school. We wish we could be satisfiedthat the action taken had any effect on the epidemic. Fewepidemiologists will be convinced by any action taken inthe middle of an outbreak unless there are untreatedcontrols for comparison. Controls in this instance were

obviously impossible, but future investigators must hopefor simultaneous outbreaks of dysentery in two similarschools. The figures suggest a daily incidence of infectionvery similar to that seen in most school epidemics whichare allowed to run their course. Sonne dysentery is not adisease which lingers, and once an epidemic is in full floodall susceptibles are infected within a few days and there-after the epidemic subsides just as this one did. It is oneof the major curiosities of epidemiology that 100%infection with any disease in any community is almostunknown. 70 children in this school were proved to havedysentery. Allowing for those not examined, a reasonableguess is that about two-thirds of the children were

infected, which is about the proportion to be expectedwhether any measure of control is applied or not.

16. Hutchinson, R. I. Mon. Bull. Minist. Hlth, 1956, 15, 110.17. Beer, B., O’Donnell, G. M., Henderson, R. J. ibid. 1966, 25, 36.