THE LANCET, JANUARY 10, 1970

These mucosal units are most commonly circular orelliptical and occasionally rectangular or hexagonal(fig. 1). The vessels are single or multiple and tend torun a tortuous course. The width of the vessels areseldom more than quarter the width of the non-vascular area of the mucosal unit. (With obliquelighting a small, refractile circular or longitudinal" pit" is found in the centre of each unit, and webelieve that this is the opening of a crypt of Lieber-kuhn.) At higher magnifications, the central pit issometimes surrounded by a slight elevation producinga " volcano" effect and the remainder of the surfaceof the unit has a roughened appearance with largerelliptical bulges, possibly representing goblet cells.Ulcerative ColitisThe variations from the normal dissecting-micro-

scope appearance were confined largely to vasculatureand consisted of: (a) faintness and blurring of thevessels; (b) excessive tortuosity, increased size of indi-vidual vessels, and widening of the vascular area (fig. 2);(c) loss of honeycomb architecture and discontinuity ofvessels; and (d) complete disorganisation with appear-ance of larger (perhaps deeper) vessels (fig. 3) and foldformation (resembling large, leaf-shaped villi). No

Fig. 2-Widened. tortuous vascular channels and less of honey-comb appearance in patient with mild ulcerative colitis.Reduced slightly from x 40.

Fig. 3-C 1· • . h 1 vessels inPat' o~p ete loss of architecture Wit argelent with florid ulcerative colitis. (X 40.)

65

CORRELATION BETWEEN APPEARANCES ON SIGMOIDOSCOPY ANDDISSECTING MICROSCOPY

Sigmoidoscopy

I Abnormal vascular pattern~ 1 characterised by one or] c:: I more of:

N ~ ~ i ! ~ I •o. "; ~ \.., "'0:"2 -5 i 15 a I,":: ~ Co not

E 0. C "'C ::! iCC I til ~ I § ti.;:: seena I~ § ~ ~ ~ : ~.::: ~ 0 ~Z i :0 ~ -e i ...l -e I .~ .~ I

I : : I ~ i '" i14i-II---2-:-;--~--0-1--3-

I i

'210 2 0 0 0 0i i

'

164,1 1000128 0 I 5 (2) 6 (3) 0 6

1 1;21 g! 4~) 6~)!; : I;I 010

1

0: 0 2._L-_2_

Normal colonRectal erythema

due to diarrhoeaUlcerative colitis:NormalErythemaGranularBleedingUlceration

Pits

Italic type shows numbers with only one abnormality.

pits were seen, perhaps because they had been pluggedby mucus; but" pit" visualisation was not always easyand the changes were too variable to be of value.Correlation with SigmoidosopyThe dissecting-microscope findings in 14 patients

with normal appearance on sigmoidoscopy and con-sidered to be free of bowel disease, 30 patients withknown ulcerative proctocolitis (classified according to.the sigmoidoscopic appearance), and 2 patients withrectal "erythema" due to continued small-boweldiarrhcea are shown in the table.

COMMENT

Immediate examination of rectal-mucosa biopsyspecimens under the dissecting microscope has provedto be a useful additional guide in the diagnosis andgrading of ulcerative disease of the colon. Alterationsin the small mucosal vessels would seem to be a fairlyconsistent finding in ulcerative colitis. The study isbeing extended to include other types of ulcerativedisease of the colon and rectum.

We thank Mr. J. Atkinson for the excellent photography.Requests for reprints should be addressed to S. B.

SUPERIOR INTELLIGENCE INRECESSIVELY INHERITED

TORSION DYSTONIA «>

ROSWELL ELDRIDGE ANNE HARLAN

Section 011 Genetics ill Epidemiology,. Epidemi?logy Branch,Collaborativeand Field Research, National Institute of Neuro-logical Diseases and Stroke, Bethesda, Maryland, U.S.A.IRVING S. COOPER MANUEL RIKLAN

Department of Neurological Surgery, St. Barnabas Hospital,New York, N.Y., U.S.A.

The association between intelligenceSummary and the recessive form of torsion

dystonia has been evaluate~ in a retrospective study.psychometric data were available fro~ a period b:foreh ppearance of symptoms for tourteen patients~i~hathis disease. Similar data were availa~le for acontrol group matched for age, sex, ethnic back-

d paper Presented at the Second Conference on the.. Base on a . d h J hClinical Delineation of BIrth Defects, he! at teo ns

Hopkins Hospital, Baltimore, Maryland, on May 26-30,1969.

66

ground (jewish), and, so far as possible, socioeconomicbackground. The mean I.Q. of the patients was 121(range 104-170) and that of their controls was 111(range 76-147).' This difference is significant (p<O·03).These data suggest that the gene for torsion dystoniaenhances I.Q.

INTRODUCTION

THERE arc probably at least two hereditary formsof torsion dystonia 1: neither has been characterisedpathologically or biochemically but there are generalclinical differences between the two. The autosomalrecessive form generally' presents between ages 4and 16 as inability to control fine movements in oneof the limbs, usually on the dominant side. Symptomsmay progress rapidly over several years and lead todeath. The gene is especially common in those ofAshkenazi Jewish background from eastern andcentral Europe. Improvement after L-dopa suggeststhat there may be a basic abnormality in biogenic-amine metabolism in this trait," In the less commonautosomal dominant form the age of onset and clinicalcourse are more variable. Neck and trunk are ofteninvolved first and torticollis may be the initial diag-nosis. Often, in the early stages of sporadic cases, theorganic basis of the abnormal movements is notappreciated, and patients undergo a period of unre-warding psychiatric treatment,"

One of us (I. S. C.) has been impressed with theintelligence and social maturity of many childrenwith this disorder.' This impression is supportedby the numerous published reports of Jewish patients,whose family history is compatible with recessiveinheritance, which invariably describe such patientsas " alert", " bright", or " of at least average intel-ligence ". To evaluate the association betweenintelligence and recessive torsion dystonia we havecompared group intelligence tests for patients, sibs,and matched controls.

METHODS

Com~encing i~ late 1966, a clinical and genetic studyof torsion dystonia was undertaken in the United Stateswith cases ascertained through neurosurgery and neurologydepartments with teaching services. We asked the parentsof all Jewish patients whose illness was suggestive ofrecessive inheritance (i.e., dystonia presenting spon-~ane.ously between 4 and 16 years of age and not presentIn either parent) for permission to use school psychometricdata of patients and their sibs. A control for each patientand each sib was obtained by selecting the next studentin alphabetical order who was the same age, sex, religion(Iewish), and, whenever possible, who attended the samep.rt~ary school. Scores were used only if the patient (orsibling) and control had had the same intelligence test inthe ~ame year. For the patient group, we analysed resultsobtained from tests given before the onset of symptoms.When more than one test result was available, the meanof the scores was used.

RESULTS

One. hundred and one patients with a diagnosis ofdystonia were. evalu~ted, and of this group thirty-nm~ we~e Jewish patients whose clinical features andfamily history are suggestive of the autosomal recessiveform of tor.sion dystonia. Useful psychometric dataare now available for fourteen of these patients and forten of their sibs plus controls for each. Of the remain-

THE LANCET, JANUARY 10, 1970

Patient group Sibling groupe-,

'§ Age at Mean I.Q. (range) Mean I.Q. (range)os Sex onset Sext1.

(yr.) Patient Control Sib Control

1 F 10·5 151 123 .. ..(131-170) (118-127) .. ..

2 F 7 ISO 121 F 125 110(120-129) (98-121)

3 M 6·5 121 92 .. ..F 16 134 114 .. ..

4 F 10 III 127 M 113 115

5 M 8 ll6 101 F 130 101(112-146) (94-109)

6 F 10 III III M 108 105(104-ll7) (106-ll4) (107-110) (101-111)

7 M 9'5 III 93 .. ..(105-117) (86-99) .. ..

F 8·5 125 139 .. ..(123-127) (131-147) .. ..

8 F 10 113 101 M 103 124(93-114) (112-13~)

F 10 123 III F 121 112(ll9-127) (104-ll7) (ll3-Bl) (104-119)

9 M 9 III 92 M llO 101(109-112) (76-107) (l03-ll6) (95-103)

F 134 11210 F 12 108 113 F 107 11211 M 9 115 116 F 135 nO

(130-139)-Total 9·7 121" 111'· 119 112(104-170) (76-147) (93-146) (94-136)-

" Differences significant at level P <0'03.

d . eder, results for five patients could not be use smcsymptoms were present when the first tests wereadministered; no data were available for four; datafor seven were not recorded in usable form; noresponse to the request was received from th~ schoo!~of five patients; and the parents of four patients elinot wish to participate. . . eli.

The I.Q. of each patient, sib, and control IS Incated in the table. Using a z-test for paired samples,the probability that' the differences in I.Q. betw~enpatients and their controls is due to chance is e~than 3%. The difference in I.Q. of clinically normsibs and their controls is not significant.

DISCUSSIONThese data suggest that recessively inherited torsion

dystonia is associated with superior intelligence. Tl;esibling group did not show a significant increas~ IIII.Q.; but, on the basis of simple mendelian segrega~o:;only two out of every three in this group woul heexpected to have the gene, and this would reduce tperformance of the group as a whole. be

Traits which may have a genetic basis reported t? Iassociated with superior intelligence include r~t1nf iblastoma ',6 and hyperuricsemia."-" Also, the sIbs Of .patients with phenylketonuria 9,10 and the parents ~epatients with childhood autism 11 are reported totheunusually bright. However, in these reports, .positive association noted may be a function of ~avoidable bias in selection of patients and/or cont;o~Also, attaching significance to I.Q. data obtained rOa group with significant handicap may be hazardous'd

By choosing controls of the same ethnic backgrohun'ed. aVan , whenever possible, the same school, we. CO"

tried to avoid a bias based on cultural and/or socloe. 11nomic background. We think any bias in th~ ~ele~~ir .of controls has been in the direction of minirOlsmg t ":d·ff . h . chose.I erences WIt patients. Also, controls were

THE LANCET, JANUARY 10, 1970

from regular schools, thereby excluding any whowould have been in special education, a factor whichmight also raise the mean I.Q. of the control group.These results are based on a small sample and

there is a 3% probability they may be explained bychance alone. However, the implications for under-standing both the chemistry of intellectual growth andthe high frequency of the gene in the Ashkenazimprompts communication at this time.Dr. Morris B. Gross, Department of Education, Hunter

Collegein the Bronx, Bronx, New York; Dr. John W. Money,JohnsHopkinsHospital, Baltimore, Maryland; and Dr. JacobA. Brody,EpidemiologyBranch, C. & F.R., National Instituteof NeurologicalDiseases and Stroke, National Institutes ofHealth,Bethesda,Maryland, assisted in the designof the study.Dr.HelenAbbey, Department of Biostatistics, Johns HopkinsHospital,Baltimore, Maryland, provided useful advice inanalysisof the data. This work was supported in part by theJohnA. Hartford Foundation and the Allan P. and JosephineGreenFoundation.Requestsfor reprints should be addressed to R. E.

REFERENCES1. Eldridge, R, Ryan, E., Brody, J. A., Cooper, I. S. in Progress in

Neurogenetics (edited by A. Barbeau and J. R. Brunett); p, 772.Amsterdam, 1969.

2. Coleman,M. P., Barnet, A. Trans. Am. Neurol. Ass. (in the press).3. Eldridge, R, Riklan, M., Cooper, I. S. J. Am. med, Ass. 1969,

210, 705.4. Cooper, I. S. Involuntary Movement Disorders, chap. 4. New

York, 1969.5. ~u~rell, R J., Josephson, T. S. Psychosomatics, 1966, 7, 368.6. Williams,M. Archs Dis. Childh. 1968, 43, 204.7. Stetton, D., Jr., Hearon, J. Z. Science, 1959, 129, 1737.8. J. Am. med. Ass. 1969,208, 1180.9. Munto, T. A. Ann. Eugen. 1947, 14,60.10.Fuller, R. in Phenylketonuria and Allied Metabolic Diseases

(edited by J. A. Anderson and K. F. Swaimson); p. 133. U.S.~ovemment Printing Office, 1967.

11.Rimland,B. Infantile Autism: the Syndrome and Its Implicationsfor a Neural Theory Behaviour; p. 23. New York, 1964.

REDUCED MUSCLE ex-GLUCOSIDASE(ACID-MALTASE) ACTIVITY INHYPOTHYROID MYOPATHY

L. J. HURWITZ D. MCCORMICKINGRID V. ALLEN

gepartmentof Neurology, Royal Victoria Hospital, andepartmentof Pathology, Queen's University, Belfast

Summary A detailed biochemical study of musclecr from a patient complaining of disabling( ~ps revealed a lowered activity of ex-glucosidaseda~ -maltase), which was the only abnormalityr~.~cted. A ye~r after the onset of symptoms hypothy-relI. sm

dwas diagnosed. Treatment with L~thyroxine

leve all sy id Iact' . mptorns, and the muscle aCI -rna taseini:~It.ywas found to be normal six months after the

latton of treatment.

I INTRODUCTIONN the folIo . .gested wing case the presentmg symptoms sug-

of 111McArdle's disease (type-v glycogenosis: lackdetail~c: phos~horylase), and for this reason a

e tochemlcal investigation was undertaken.

1\ fir CASE-REPORTStiffnes: ~ffi~er,aged 28 years, noticed painful cramps andtrampsa~ t e muscle with exercise in January, 1968. ThelareXe • ected only those muscles involved in any particu-

rcise and w h H'tlterciset I ere not affected by cold weat er. ISo erance progressively decreased, and some six

67

months after the onset he would have severe cramp onwalking 100 yards or after gripping objects for a few min-utes. During this period he became aware of considerablemuscle development with an increase in weight of 2-3 stone(12-18 kg.). From being a man of slender frame he de-veloped the physique of a professional weight-lifter thoughhe never engaged in any body-building activities. During1967 and 1968 he had nine brief episodes of central chestpain accompanied by breathlessness. On examination themost notable finding was the massive enlargement of allmuscle-groups: there was no obesity and the muscles werenormal on palpation. The initial muscle action was alwaysstrong, but weakness with the onset of severe cramp fol-lowed sustained activity. During the cramp the appropriatemuscles became tender and were shortened, and electro-myography revealed motor-unit potentials so that the short-ening was due to muscle contraction and not contracture.The thyroid was palpable but not enlarged; There were noother abnormal signs either in the nervous system or ongeneral examination. Electrocardiograms (E.C.G.) takenover intervals showed low-voltage or inverted T waves in allleads and QRS complexes of low-normal amplitude. InApril, 1969, the patient began to complain of some intoler-ance to cold, and it was noted clinically that the skin wasexcessively dry with keratosis of the hands and there wassome coarseness of the voice. The ankle-jerk reflex-timewas normal. Primary myxa:dema was diagnosed clinically,and this was confirmed by tests of thyroid function. OnMay 3 daily r.-thyroxine therapy was started; the initial dosewas 0'05 mg. and this was increased over 18 days to amaintenance dose of 0'2 mg. Within 4 weeks of first takingthe L-thyroxine the patient could exercise lightly withoutcramps. The E.C.G. 31/2 months after the start of treatmentwas entirely normal. On examination in October, 1969,21months after the onset of symptoms, he had no complaintsand was back at work. Muscle bulk had decreased, andforearm girth was 3 ern. less than in September, 1968.Investigations

The following were normal: full blood -count; Wassermanreaction; glucose-tolerance test; glucose-assimilation test;lactate increase on ischremic exercise; serum electrolytes,urea B12, folic acid, alkaline phosphatase and carotene;blood-pH before and after exercise; urinary creatine/creatinine ratio; n-xylose excretion; urinary aminoacids;

20~----------------------~--1

16

N

'~ 12l(

~:::~ 8

4

L2 Tt tLI

toL---_J~~b--~"~--~A~P~~~~M~a:y_'~J:un:e~Jan. Fe. ...ar.Fig. I-Work tolerance on handgrip ergometer.

LI L2=start and withdrawal of low-carbohydrate diet.T=s~art of L-thyroxine therapy.