CASE REPORTSCONGENITAL HEMI-ATROPHY

BY

LILLY H. ZONDEK, M.D.

Not much detailed information is available as tothe causes and origin of structural asymmetries.Congenital hemi-atrophy is a rare developmentalabnormality in which parts or all of one side of bodyare of diminished size. As a rule all tissues areaffected to a similar extent. The condition shouldnot be confounded with the unilateral atrophyassociated with motor disorders such as unilateralparalysis and unilateral athetosis.

In 1927, in a survey of world literature, startingfrom 1859, Kraus and Perkins found only eightcases of congenital hemi-atrophy in five of whichthe whole side of the body was affected. The otherthree were confined to the leg in two cases, and tothe face and leg in one case. More cases have beenreported since, and in 1939, in another survey ofworld literature, Landauer found twenty-two casesof congenital hemi-atrophy, eight of which onlyshowed an affection of the whole side of the body.

Congenital hemi-hypertrophy is, in many ways,the counterpart to congenital hemi-atrophy.Although also a rare condition, more cases of hemi-hypertrophy have been reported than of hemi-atrophy. Both conditions are sometimes associatedwith retardation in mental development and withvasculo-cutaneous disturbances, but these are metwith much less frequently in unilateral atrophy thanin unilateral hypertrophy. Perhaps these two latteraffections are not caused by two different agents, butby either hypo- or hyperfunction of the same agentrespectively.The mechanism which brings about preferential

asymmetry seems to act during a comparativelyearly stage of embryonic life. Probably the agencyresponsible for developmental asymmetry must belooked for within the developing embryo, and notin conditions of the uterine environment, as somany different structures are affected.. Variousauthors assume that the central nervous system hasa trophic function in development and that thusunequal differentiation of cerebral centres maymodify growth asymmetrically. Kraus and Perkinshold the view that cerebral portions of the visceralnervous system exert a trophic control not only onglands and smooth muscle but also on striatedmuscle, tendons, bone, skin, hair, in short, on alltissues of the body. They assume that these centresare located in the hypothalamic region in or aboutthe floor of the third ventricle, as well as in the cell

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groups lying about the tuber cinereum. Further-more, it is now also generally believed that from cellgroups in the posterior part of the hypothalamus adirecting influence is exerted over the function andtrophic activities of the sympathetic system. Onthe other hand, evidence has been obtained thatdysfunction of the sympathetic can be the cause ofunilateral atrophy. Cases of facial hemi-atrophyhave been reported associated with changes in thesympathetic on the affected side.From this point of view it may be of interest to

discuss some conditions which are frequentlyassociated with unilateral atrophy. There are, tobegin with, two clinical conditions in which hemi-atrophy is frequently met with, chondrodysplasia(Ollier's disease) and scleroderma. With regard toboth these affections theories have been broughtforward which assume that dysfunction of thesympathetic plays an important part in their patho-genesis. Furthermore, various instances of pro-gressive (non-congenital) facial hemi-atrophy havebeen reported which show a definite relation tochanges in the sympathetic system on the affectedside. There are, lastly, various instances of totalor partial hemi-hypertrophy associated with vasculo-cutaneous abnormalities, and which have beenattributed to unbalanced action of the sympathetic.Of these conditions Ollier's disease will be more

fully described here as the case reported belowshowed some bone changes similar to those seen inchondrodysplasia.

Chobdrodysplasia (Oiier's disease)Chondrodysplasia is an osseous dystrophy affect-

ing the long bones and the metacarpophalangealskeleton. In some cases the vertebral bodies havealso been found to be affected. (The osseous changescan be demonstrated by skiagram.) It is an affectionof growth with arrest of growing parts of theskeleton. Ollier (1899) emphasized as an outstand-ing clinical character of the disease an asymmetricalinvolvement of the body, a ' one-sidedness.' Oneof the essential features of the disease is the retarda-tion of growth of one or both limbs on the affectedside, sometimes associated with compensatoryscoliosis. The term ' Ollier's disease ' has now beenconfined by a number of authors to those cases ofosseous dystrophy which show an asymmetricalinvolvement of the body as an outstanding clinicalfeature.

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6ARCHIVES OF DISEASE IV CHILDHOODChondrodysplasia usually starts in early life.

Cleveland (1928) describes a case i w-hich the firstsigns of asymmetry were noticed at the age of sixmonths, so perhaps the determining agent beginsto act during embrvonic life. The affection isprogressi- e for several years but later on tendsto heal spontaneously, and in the later years ofchildhood the limbs on the affected side grow at thesame rate as the limbs on the sound side.Nothing definite is yet known as to the patho-

genesis of chondrodysplasia. Bentzon (1924) holdsthe view that Olfier's disease represents the typicalreaction of the bone to certain disorders in theinnervation of their blood-xvessels. He also stressesthe fact that the affection is often confined to onehalf of the body. From an experimental stand-point, A-orking with rabbits, he was able, by inter-rupting the sympathetic nerves to produce in severalinstances structural changes similar to those seen inOilier's disease. Murk Jansen (1928) believes thatchondrodysplasia is the result of a retardation ofthe differentiation of cartilage cells consequent upona deficient blood-supply which may be due to v-aso-constriction from faulty action of the sympatheticnerves. It may thus be concluded that, perhaps,sympathetic dysfunction plays an important part onthe pathogenesis of Ollier's disease.

SclerodermaScleroderma is now considered by many authors

to be an angiotrophoneurosis in which unilateralatrophy frequently develops as a secondary symptom.If the disease starts during youth, the growth oflimbs on the affected side may suffer.

Cockayne (1916) found several instances of com-plete hemi-atrophy (non-congenital) with sclero-derma of the atrophic parts of the body. Meyer(;1936) assumes that the common cause for hemi-atrophy and scleroderma may be looked for in anabnormal function of the sympathetic system, whichreacts in some instances by causing scleroderma, inothers by causing a hemi-atrophy or a combinationof both abnormalities according to the part of thesympathetic which is particularly affected.

Facial hemiatrophyIn 1846 Romberg described a case with wasting

of one side of the face. He called this affectionfacial hemi-atrophy' as a proof for the existence

of trophic nerves.

Jendrassik (1884) assumes that the cause of facialhemi-atrophy is a lesion of the sympathetic cervicalganglia or of the fibres of Remak connected there-with, whereas Archambault and Fromm (1932) areof the opinion that sympathetic implication is itsonly underlying cause. This view has been con-firmed by clinical observations. Bruining and Kroll(Meyer, 1936) found alterations in the ganglion cervi-cale superiorin some instances offacial hemi-atrophy.Manthey (1928) reported a case of facial hemi-atrophy developing after cut-injury of the cervicalsympathetic and in a case reported by Bost (1927)the cervical sympathetic had been injured byfracture of the clavicle.

Although in all these instances the hemi-atrophyis affecting the face only, and is mostly of a non-

congenital type, they may fumish a proof for theessential part w-hich the sympathetic system plays inthe pathogenesis of unilateral atrophy. The con-dition is strictlv unilateral. It extends gradually,involving skin, fat and subcutaneous tissues untilthe entire side of face is affected. The bones showretarded growth or atrophy.

Hemi-hypertrophy and vasculo-cutaneousdisturbances

Congenital hemi-hypertrophy is frequently associ-ated with X asculo-cutaneous disturbances, e.g.pigmentation or haemangioma. Furthermore,diffuse angioma are often accompanied by localgigantism or partial hemi-hypertrophy. It has beenassumed that this unilateral overgrowth might bethe result of an unbalanced action of the sympa-thetic system, giving rise to an inequality in bloodflow or distribution.

Report of caseJ.E. a boy, aged 11 vears, was admitted to the

Queen Elizabeth Hospital for Children, Bayford,Herts., in January 1944.

Family history: The patient's mother is healthy,but ' highly strung.' The patient's father, whodeserted the mother soon after the child's birth, issaid to have been healthy and nothing abnormal hasbeen reported in his family. No physical or mentalabnormality can be determined in the mother'sfamily.

Patient's history: The patient, an only child, wasa full-term infant. His was an instrumentaldelivery. Birth-weight was 5 lb. 6 oz. He wasbottle-fed. No definite date is available as to thestarting of dentition, but he is said to have acquiredhis teeth rather early. He sat up when ten months'old, began to talk at fourteen months and startedwalking with support of a specially constructedorthopaedic boot at the age of two years. He hashad measles, rubella, mumps, whooping-cough andchicken-pox.At birth the child presented a marked under-

development of the right side of the body. Theright side of the face was much smaller and flatterthan the left one, the right arm and leg showed aremarkable shortening, he had a dorsal scoliosis tothe right and a kyphosis. Testicles were absentfrom scrotum. During the first year of life theatrophy of the right side of the face became graduallvless marked. During the following vears. accord-ing to his mother's statement, this did not increaseto any remarkable degree, the rate of growth of bothapparently almost keeping pace with each other.The kyphoscoliosis, however, became much moreconspicuous. He was treated in various hospitalswhere he received all sorts of endocrine therapy(elityran. ant. lobe pituitary hormone), as well asosteopathic treatment, but with no success. Hecould move all limbs well and never showed anvparalysis. Mentally he was bright and intelligentand went to a normal school until September 1943,where he was backward in physical attributes butappeared mentally alert. Since then he has beentaught at home.

Examination: The patient is a small bov, hisheight corresponding to that of a child aged fix-e

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A CASE OF CONGENITAL HEMI-ATROPHY

years. The most marked deformity, at first sight,is the conspicuous kyrphoscoliosis. The face issomew hat asymmetrical, and the right arm and legare shorter and thinner than the left ones. Hewalks with a limp, owing to the shortening of theright leg.HEAD: The head is of normal shape. The face

show-s some degree of asymmetry, the right sidebeing somewhat flatter and smaller than the left.CRANIAL NERVES:1st to 10th: Normal.11th nerve: Function of both sternomastoid and

trapezii muscles somewhat restricted, but this isprobably mostly due to the deformity and fixationof the spine which does not allow free movements.

12th nerve: Tongue protrudes in midline. Nofibrillation.

TEETH: The teeth are sound, but rather crowdedtogether and in bad position.THROAT: Normal.NECK: The neck is short, owing to the deviation

to the left of the cervical spine. Movementsrestricted.THORAX: The thorax is grossly deformed. The

shoulders are kept high, the right one slightly higherthan the left one. The upper thoracic spine showsconsiderable lateral deviation with the convexity tothe nrght, the cervical and the lower thoracic spineshow a compensatory scoliosis with the convexityto the left. There is a conspicuous kyphosis of thedorsal spine. The sternum protrudes considerably,thus causing a vaulted appearance of the anteriorwall of the chest. The inferior angle of the rightscapula is somewhat higher and farther from themiddle line than that of the left scapula.HEART: The heart is displaced upwards and out-

wards. The dullness extends over an almost quad-rangular area, the lower border running in the thirdintercostal space from the left sternal border to justoutside the midclavicular line, the upward borderrunning almost parallel in the first intercostal space.The apex beat is palpable in the third intercostalspace, I in. outside the midclavicular line. Allsounds are normal. The pulse is normal in volumeand rate. B.P. 95j60 mm. Hg.

RESPIRATORY SYSTEM: The percussion note overthe right side of the chest is hyperresonant, more soanteriorly than posteriorly. The percussion note isnormal over the left lung. Breath sounds arefeeble, especially posteriorly, but everywhere thereis normal vesicular breathing. Respiration rate isnormal.ABDOMEN: The abdomen is flat. Muscular de-

velopment fairly good. Liver and spleen notpalpable. Abdominal reflexes present and equal.Both testes are absent from the scrotum and cannotbe felt in the inguinal canal. No hernia.

EXTRE-MITIES:Arms: Left arm normal.Right arm: The right arm is shorter (2r. in.)

and thinner than the left. The palm and thenareminence are flattened. The middle phalanx of thering finger shows a slight lateral abduction, whereasthe distal phalanx is kept in a slightly flexed position.The little finger is small and shows a marked con-traction, with palmar flexion in both phalangealjoints, and slight dorsal flexion and ulnar abductionin the metacarpo-phalangeal joint. All movements

with the exception of the ring- and little finger, arenormal and not restricted, but there is some degreeof decreased muscular power as compared with theleft arm.

There exists some laxity of the elbow' joint and.especially, of the metacarpo-phalangeal joint ofthe thumb, thus allowing hyperextension. Allreflexes are normal and equal on both sides. Thepatient is left-handed.

LEGS:Left leg: Normal.Right leg: The right leg is shorter (23, in.) and

thinner than the left one. All movements arenormal and not restricted, but the muscular poweris somewhat decreased in comparison to the left leg.All normal reflexes present and equal. No abnormalreflexes.

The7e is no evidence of ataxia or dysergia. Notremors, twitchings, choreiform movements ormuscular spasms are present. All tests for touch,pain, temperature, vibratory, muscle, bone andtendon sense elicit normal and accurate responses.THE SPEECH is normal.THE SKIN is smooth, of normal consistency and

there is no hyperhidrosis. The scalp hair is denseand equally distributed.

SLEEP: Normal.APPET1TE: Normal. Patient does not suffer from

abnormal thirst.MICTIJUTION AND BOWEL ACTION: Normal.

MENTAL coNDmoIN: The patient is of averageintelligence. He is bright and alert, but rather un-stable emotionally and will break into tears on theslightest provocation. He is noisy, over-talkativeand boisterous and tries to attract attention by everyconceivable means. When together with otherchildren he adopts a domineering and provoking, attimes even aggressive attitude. He is witty, althoughin a somewhat affected manner. He draws ex-tremely well. He gets on well with younger children,who admire him because of his witticisms and amongwhom he quickly makes himself the centre of atten-tion, but he has difficulties in aijusting himself tothe company of children of his own age group whoare inclined to resent his boastful, provokingbehaviour and, in their turn, deride him because ofhis physical deformity.

X-ray examination:SKULL: There is a slight flattening of the right

side of the skull. Other-ise the skull is normal.Pituitary fossa normal (fig. 1).THORAX: There is a gross deformity of the upper

dorsal spine and upper right ribs, with markedkyphoscoliosis convex to the right with a wedge-shaped deformity of the vertebral bodies. There issome degree of compensatory scoliosis convex tothe left of the cervical and lower dorsal spine. Theupper thoracic vertebral bodies show a deficiencyin bone structure, with abnormal ossification, andcontain irregular strands of calcareous material.Their cortex is thin and irregular, and there appearsto exist some fusion between II and 1II, and IV, V,VI and VII. The right ribs are thin and atrophic,especially the upper six, and take a downwardcourse. forming an acute angle with the vertebralbodies. The fourth to eighth left ribs are crowded

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FIG. 1

FIG. 2

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together and their intercostal spaces are narrow(fig. 2-4).The lumbar spine appears to be normal.The right os ilium is smaller than the left one.EXTREmrTIES: All bones are slender. The bones

on the right side, including the carpal and tarsalbones, are smaller and thinner than the left ones.There is some lateral abduction of the middle anddistal phalanges of the right ring finger, and markedplantar flexion of the middle and distal phalanges ofthe right little finger. with abduction of the Istphalanx. The middle and distal phalanges of thisfinger show a high degree of atrophy. Both feet aresmall, the right one smaller than the left one, butotherwise well developed. The bone structure is

normal, the development is normal for the age andthere is no delay in ossification (fig. 5-9).

ARMS: RightLength of whole arm .. .. .. 18!Humeral-clavicular juncture to lateral

condylus humeri .. .. .. 8Lateral condylus humeri to styloid

process of radius .. .. .. 6Radio-carpal joint to tip of middle-

finger.. 4Circumference upper arm .. .. 6Circumference forearm .. .. 5

LEGS:Total length of leg 21

Spina iliaca ant. sup. to medialmalleolus 23.. . . 23

Trochanter maj. femoris to lat. con-dyle of tibia .. .. .. .. 11

Lateral condyle of tibia to lat.malleolus .. .. .. .. 9

Medial condyle of tibia to medialmalleolus .. .. .. .. 9

Medial malleolus to top of big toe .. 4Circumference thigh .. .. .. 10

Circumference lower leg 7* *

.4

MEASUREMENTS (IN- INCHES)Length of body (standing on both legs,

without correction of the shorteningof the right leg) ..

Normal length of a child 11 vears oldVertex to symphysis ..

RightSymphysis to sole 21!

Proc. zygomaticus to chin .. .. 3

42!5421Left23232 FIG. 4

A CASE OF CONGENITAL HEMI-ATROPHY 39

Left21

9

7

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24

25

12

10!10512L81

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J1

FIG. 5

Laboratory examinationsURINE:

Specific gravity: 1023.Deposit: Nothing abnormal detected.Total output within 24 hours: 1280 c.c.

BLOOD:Erythrocytes .. .. .. 4,560,000 per c.mm.Haemoglobin .. . .. 82 per cent.Colour index .. .. .. 0-9Leucocytes .. .. .. 8,600 per c.mm.Polymorphonuclears .. .. 61 per cent.Lymphocytes .. . 32 per cent.Mononuclears .. .. 6 per cent.Eosinophils .. .. I per cent.Basophils .. . .. 0

SUGAR TOLERANCE: Blood sugar(mgm. per cent.)

0 hours (23 gn. dextrose by mouth) .. 97l hour .. .. .. .. .. 1701 hour ..... . . . . 1311 hours .. .. .. .. .. 1032 hours .. .. .. .. 95

Summary and conclusionThe case under discussion is a total congenital

hemi-atrophy in a boy aged eleven years, affecting

the right side of the body, with a high degree ofkvphoscoliosis. The body length corresponds tothat of a child five years old, but this is probably dueto the deformity of the spine. The extremities onthe sound side are of about the normal length for achild aged eleven years. The long bones and themetacarpo-tarsal skeleton on the affected side areshorter and thinner than the ones on the sound side,but the bone structure, as seen by x-ray, is normaland there is no delay in ossification. The under-development is not confined to the bones alone, butalso affects the soft tissues, as shown by the lessercircumference and the decreased muscular power ofthe limbs on the right side. The upper six right ribsshow a high degree of atrophy. The vertebralbodies of the upper thoracic spine, especially II toVII, show gross deformity and abnormal structureof the bone tissue. Their appearance with the thin,irregular cortex, the deficiency of bone structure,with irregular strands of calcareous material, issimilar to the changes seen in Ollier's disease. Theextreme degree of wedge-shaped deformity is, ofcourse, mostly due to the kyphoscoliosis which, in

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its turn, is partly due to the postural disturbancesexerted by the underdevelopment of the right sideof the body. It is possible, however, that the softconsistency of these bones, caused by the osseousdystrophy, played a part in aggravating theirdeformity.The patient showed two more abnormalities, the

contracture of the right hand little finger andcryptorchidism. The contracture of the little finger,with fixed palmar flexion of the middle and distalphalanges and slight dorsiflexion of the proximalphalanx, and the slight palnar flexion of the middleand distal phalanges of the ring finger, lead to thesuspicion that this is a congenital contracture of theaffected fingers, which is a comparatively common

inherited deformity. It has been suggested thatthis abnormality is probably due to imperfect de-velopment of the anterior ligament of the first inter-phalangeal joint. Regarding the cryptorchidism itcannot be determined here whether this conditionis due to hormonal deficiency or to anatomicaldeficiency. The former is the more common causeof undescended testicles, but lately the fact has been

6

stressed that anatomical defects appear to play animportant part in many cases of cryptorchidism.One further note may be made here about the

patient's mental make-up. His very noisy, boastful,provoking and. at times, aggressive behaviour canbe explained as a defence mechanism. By over-stressing his mental capacities he tried, uncon-sciously, to counteract the feeling of inferioritycaused by his physical deformity. He thus 'over-compensated his inferiority-complex.' As a conse-quence, his social adjustment with children of hisown age-group was rendered rather difficult.Nothing definite can be said regarding the patho-

genesis of this case. The factor determining theunderdevelopment of the right side must have actedduring embryonic life as the hemi-atrophy wasfound to be present at birth. Furthermore, theaction of this agent was probably mostly confined tothe period of intrauteine development, as thediscrepancy in length between the two sides of thebody is said not to have much incrased after birth.An influence by the pituitary gland cannot be

excluded. But one of the main features of hypo-

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FIG. 7

physeal dwarfism is unimpaired symmetry of thebody. The cryptorchidism in this case may be asymptom of hypopituitarism, but, on the otherhand, the incidence of this abnormality is high andit cannot therefore be concluded, from this factalone, that the hemi-atrophy is due to hypophysealdeficiency, i.e. lack in growth hormone. Besides,that would not explain the unilaterality of theaffection.

It has been suggested that cerebral portions of thevisceral nervous system exert a trophic control onall body tissues, perhaps partly via the sympatheticsystem, and may thus influence growth asymmetri-cally. It has also been shown that facial hemi-atrophy may be brought about by changes or injuryof the sympathetic on the affected side. It hasfurther been mentioned that scleroderma which isfrequently associated with hemi-atrophy as a

secondary symptom, may have its origin in anabnormal function of the sympathetic system.

FIG. 8

Lastly it has been pointed out that sympathetic im-balance may play a major part in the pathogenesisof chondrodysplasia, in which a unilateral arrest ofgrowth is frequently met with. From that point ofview one further note may be made regarding therelations existing between congenital hemi-atrophyand Ollier's disease. In both affections the re-sponsible agent acts during early life. Hemi-atrophy is congenital (as in the reported case).Oilier's disease starts in infancy or early youth (thecase reported by Cleveland showed the firstsymptoms at six months), i.e. it may already bepresent at birth. Both conditions are not pro-gressive during the whole time of adolescence. Inthe reported case of hemi-atrophy the growth ofboth sides apparently almost kept pace with eachother after birth. Oilier's disease usually comes toa standstill in the later years of growth. Oilier'sdisease is frequently (according to several authorsalways), confined to one side of the body and the

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A CASE OF CONGENITAL HEMI-ATROPHY 43

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wF 9

FIG. 9

affected limbs show an arrest in development. Bothunilaterality and underdevelopment are the mainfeatures of hemi-atrophy. Furthermore the re-ported case showed changes in several vertebralbodies similar to those seen in Oilier's disease. Itthus appears that some relationship might existbetween these two abnormalities.A final conclusion regarding the etiology of con-

genital hemi-atrophy can, however, not be given. assome still unknown morphogenetic factor is probablyconcerned.

Thanks are due to Mr. H. W. S. Wright, Hon.Surgeon to the Queen Elizabeth Hospital forChildren, Bayford, Herts., for the opportunity toexamine this case and for his permission to publishit, and to Sir John Fraser, Royal Infirmary, Edin-burgh, for his kind help and assistance.

REFERENCES

Archambault. N., and Fromm, N. K. (1932). Arch.ANeurol. Psi chiat., Chicago, 27, 529.

Bentzon, P. K. G. (1924). Acta radiol., Stockh., 3, 89.Bost. C. (1927). Arch Pediat., 44, 497.Briuning and Kroll. Quoted by Meyer, H. E. (1936).Cleveland. M. (1928). Surg. Gvnaec. Obstet., 47, 338.Cockayne, E. A. (1916). Brit. J. Child. Dis., 13, 225.Jansen, M. (1928). The Robert Jones Birthday Volume,

Oxford, p. 43.Jendrassik, E. (1884). Dtsch. Arch. klin. Med., 59.Kraus, W. M., and Perkins. 0. C. (1927). Arch. Neurol.

Psi chiat.. Chicago, 18, 249.Landauer, W. (1939). Hum. Biol., 11, 4.Manthey, P. (1928). Z. ges. Neurol. Psechiat., 114, 192.Meyer, H. E. (1936). Med. Klinik., 32, 352.Ollier, L. X. E. L. (1899). Bull. Soc. Chir. Lyon, 3, 22.Romberg, E. (1846). Klin. Ergebnisse, 75.

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