AUTISM AND RETT SYNDROME: BEHAVIOURAL INVESTIGATIONS AND DIFFERENTIAL DIAGNOSIS

Bo Olsson Andreas Rett

This paper is a follow-up to our previous study of behavioural observations in the differential diagnosis between Rett syndrome and infantile autism (Olsson and Rett 1985). The syndrome was described originally by Rett (1966, 1969), but did not gain wide recognition until after the publication in English of a study by Hagberg and colleagues, who had discovered it independently (Hagberg et al. 1983).

Criteria for Rett syndrome include: (1) female sex; (2) early behavioural, social and psychomotor regression (a loss of achieved abilities), development of com- munication dysfunction and signs of dementia; (3) loss of purposeful hand skill, accompanied by hand-wringing (‘hand-washing’) stereotypies, and the appearance of gait apraxia and truncal apraxia/ataxia between the ages of one and four years; and (4) normal head circumference at birth, but later deceleration of head growth (and by inference brain growth) between the ages of six months and four years (Rett 1966; Hagberg et al. 1983, 1985). Autistic traits in the first year of life (Nomura et al. 1984) are accompanied by a high degree of developmental retardation (Rett 1966, Hagberg et al. 1983, Nomura et al. 1984, Olsson and Rett 1985), associated with pseudo-autistic abnormalities (Rolando 1985).

The most common wrong diagnosis of children with Rett syndrome above the age of one year has been infantile autism (Kanner syndrome), and most probably this is still the case in many places. The most obvious reasons for this false diagnosis are the stereotypic movements of the children, their poor interaction with their social environment and smiling or laughing without apparent reason.

Kanner syndrome can be observed

may also result from organic disturbances such as brain damage in early childhood,

without any neurological findings and ? metabolic disorders or biochemical %-

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defects (Asperger 1968, Lempp 1972, 00

syndrome are diagnosed as autistic, very 5 likely there are additional factors e

3 is 2 patients, is not pathognomic and a very

similar behaviour pattern can be observed $ in other organic brain syndromes s (Rolando 1985). According to results of clinical and laboratory examinations (Rett 1966, 1969; Hagberg et al. 1983; Nomura

2 et al. 1984; Rolando 1985; Kerr and Stephenson 1985) such traits as motor 2! stereotypies together with symptoms of B

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s including severe brain damage and such corollaries as severe mental retardation and motor disorders. The psychological profile, though homogeneous in all

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motor and intellectual retardation should also be investigated. 429

The most characteristic stereotypies in children with Rett syndrome are their monotonous ‘hand-washing’ movements, and pressing the hands together in front of the chest or chin, frequently also putting the fingers or hand into the mouth and wetting the fingers with saliva. If objects are still gripped, they are often put into the mouth. Other characteristic traits are a broad-based stance or gait and episodic hyperpnoea through the open mouth.

In most cases head control develops normally in the first year of life but motor milestones such as sitting unassisted or standing and walking with or without support are delayed. The maximum basic motor performance is variable (Nomura et al. 1984). Rolando (1985) noted that patients’ histories always showed apparently normal psychomotor develop- ment for at least the first nine months of life, followed by slowed development of postural and cognitive acquisitions, so that by the age of 18 months all the girls were obviously retarded. Rapid deterio- ration occurs in the second year of life, followed by very slow progression of the disease. Movements become slower and dystonia and hypotonia eventually turn to akinesia and rigid spasticity, the latter more pronounced in the lower than in the upper limbs.

Nomura and colleagues (1984) suggested that autistic traits in early infancy such as extreme quietness, long daytime sleep, lack of eye-contact or responsiveness, lack of interest in the environment and decrease of muscle tonus develop as the earliest symptoms of Rett syndrome in all cases. Thus onset may occur as early as the first months of life. The autistic traits are soon overlaid by profound mental retardation and regression. However, according to the parents we have questioned, no such behavioural traits had been observed before their children’s first birthday.

The onset of Kanner syndrome is always discernible before the age of three years (Anthony 1958). Austistic be- haviour resulting from organic damage, sensory defects, metabolic disorders or severe mental retardation also frequently starts before the age of three.

430 Kerr and Stephenson (1985) estimated

the incidence of Rett syndrome to be one in 30,000 live births (i.e. one in 15,000 girls). The complex psychic and neuro- logical symptomatology presents difficult problems in differential diagnosis be- tween primary autism, mental retardation with autistic behavioural features and progressive organic brain disorder (Rolando 1985). The purpose of the present paper, therefore, is to expand on our 1985 report by identifying behavioural traits that can be observed in Rett syndrome but not in the autistic syndrome. We have checked the results of our previous study and have also examined further patients not included in that investigation.

Patients We compared the behavioural traits and mental development of 27 children with Rett syndrome with those of 18 children diagnosed as having infantile autism (Kanner syndrome) and a further 18 children who exhibited autistic traits as a result of severe organic brain damage. The diagnoses, which were known to the examiners, were arrived at after the following examinations had been com- pleted: neurological examinations; EEG; blood chemistry; psychological tests; his- tory taking; audiological and visual test- ing; and anthropological measurements.

As mentioned in our earlier study, our diagnosis of Kanner syndrome was based on a set of criteria outlined in the film ‘Diagnosis of Early Infantile Autism’*. For autism to be diagnosed, at least seven of the 14 criteria listed in Table I must be present. According to the film these characteristics are relatively independent of age, and this agrees with our own experience.

We divided the children with Rett syndrome into four age-groups: Group I: 1 year 10 months to 3 years 1 1 months. In this period the characteristic stereotypies develop while most of the girls still learn some accomplishments, e.g. walking. Group 11: 4 years to 6 years 11 months. The stereotypic movements and charac- teristic postures are developed but

*From Sandoz: scientific direction by Professor J . Rendle-Short, University of Queensland, Herston, Queensland, Australia.

progression of the disease is either very slow or not observable. Group 111: 7 years to 8 years 1 1 months. The children’s movements are slower and there is less hyperactivity with the exception of the stereotypies. Group IV: 1 1 years to 14 years 11 months. There is rigid spasticity with increased muscle tone and akinesia, although according to the parents it is easier for them to communicate with their children.

The patients with Kanner syndrome and those with autistic traits related to infantile brain damage were divided between groups 11, I11 and IV (Table 11). There were no children in the study aged between nine years and 10 years 1 1 months; all the children were female.

Method Each patient was seated in front of a table in such a way that the hands could rest comfortably on the table-top. The children’s parents were present in most cases of Rett syndrome and in some cases of Kanner syndrome and of brain- damage-related autism. The following 10 stimulus situations were presented to each child: (1) A small red woollen doll was ‘walked’ by the examiner on the table in front of the child. (2) A red and green top was placed on the table; if the child did not try to grasp the top, the examiner rotated it (see Fig. 4). (3) The top was hidden from view by placing a small open-topped box upside- down over it within reach of the child. (4) Raisins or small biscuits were presented; if the child did not try to grasp them, the examiner put some of them in his own mouth in front of the child. ( 5 ) The raisins or biscuits were hidden, as with the top. (6) A small white ball made of polystyrene was presented; if the child did not try to grasp it, the examiner rotated it like the top and bounced it on the table. (7) The ball was hidden, as with the top. (8) A paper bag was presented and crumpled by the examiner. In each of the stimulus situations (l), (2), (4), (6) and (8) the object was first presented in front of the child, within direct view but out of reach. Then it was placed on the table directly in front of the

TABLE I The 14 characteristics of infantile autistic syndrome (Kanner syndrome).

1. Infant has severe problems in making contact with others

2. Acts as if deaf but responds actively and positively to music

3. Resists invitations to learn new things 4. No fear of real dangers 5 . Resistance to divergence from the familiar 6. Expresses wishes through gestures 7. Giggling and laughter without evident cause 8 . Rejects caressing and tenderness 9. Physical hyperactivity

10. No eye contact 1 1 . Excessive attachment to certain objects 12. Rotates small objects 13. Stereotypic playing habits 14. Isolation

*From Olsson and Rett (1985); reproduced by permission.

child, within reach. This procedure was repeated four times; if at some point the child grasped the object, we took it away from her and started the procedure again from the beginning. If she still tried to grasp the object at the fourth presentation, she was not prevented from doing so, in order not to frustrate her. If, however, she made no attempt to grasp it, the object was put into her hands. The raisins and biscuits were also placed into the child’s mouth. (9) A small bell was put onto the table out of the child’s reach. If she did not try to reach for it, the bell was placed within her reach. Then the examiner, standing behind the child, rang the bell alternately on the left and right side of her head at a distance of about half a metre. Then he called the child’s name from one side of her (left or right) and simultaneously rang the bell, holding it at the opposite side of her head (see Fig. 5) . After that, the bell was placed on the table again in front of the child and out of her reach. If she still did not try to grasp it, it was placed in her hands. (10) The examiner called the child’s name in a soft voice and turned his face toward her, gently stroking her cheek. This was regarded as both a tactile and a social stimulus situation.

In each of the situations we recorded: (1) the number of times the child looked at or grasped an object and the length of

0; N

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4 L 5 4

431

TABLE I1 Numbers of children in different age-groups

Group I I1 III IV Age range (yrs:mths) I:10-3:11 4:OO-6:11 7:OO-8:11 I1 ~00*-14~11

Rett syndrome 6 9 5 1 Primary autism

7 5 6 (Kanner syndrome) -

Brain damage 6 7 5 (with autistic traits) -

*There were no children in the study aged between 9:O and 1 O : l l .

time she looked at or handled it; (2) if the child tried to grasp an object out of reach or to take a hidden object from under the box; (3) how the child handled an object, e.g. shaking it, dropping it or putting it into her mouth; or if she handled the object according to its function, e.g. ringing the bell, rotating the top or crumpling the paper bag; and whether she ate the raisins or biscuits; (4) if the child looked at the examiner (or at another person present) or if she turned her head away, and the duration of any eye- contact; ( 5 ) the expressions on the child’s face; and (6) any speech utterances, e.g. syllable-like utterances, words, sentences or echolalia.

We tried then to determine to which stage of ‘sensorimotor intelligence’, according to the theory of Piaget (1952), the observed behaviour in the various stimulus situations corresponded.

According to this theory, behaviour would correspond to the third stage if the child looked at an object, grasped it and then either let it go again or placed it in her mouth; all objects would be equally handled but not for their specific functions. In ’ normally developing children such behaviour is first seen between the ages of four and six months, when they are beginning to develop their eye-hand co-ordination.

Behaviour would correspond to the fourth stage if, for instance, the child lifted the box to reach for an object which had just been hidden underneath it within her view, thereby demonstrating both that she can separate ends and means, and that she can imagine an object which has

first be observed in normally developing children between the ages of seven and 10 months.

Behaviour would correspond to the fifth stage if, immediately after per- ception of an object, the child used it for its specific function (e.g. ringing the bell or rotating the top). Such performances are first seen in normal development between the ages of 11 and 14 months.

Autistic children have many different stereotypic movements; all such stereotypies, tics and self-injuring activities were recorded and described in detail. At the same time, different patterns of movements and postures were recorded and categorised as follows: Speed of movements: (1) slower than normally seen at this age; (2) normal for age; (3) sudden stopping or starting of movements, or more often faster move- ments than normal for age. Amount of movements: (1) a small number of spontaneous movements, apart from the stereotypies; (2) move- ments according to age; (3) hyperactivity such as frequent and fast moving about and greater frequency of grabbing objects. Facial expressions (‘mimia’): (1) constant expression (‘amimia’) or rare changes of expression (‘hypomimia’); (2) according to age; (3) vivid, strongly emotional expressions and grimacing (‘hypermimia’). Co-ordination of movements: (1) ataxia, with tremor of upper limbs or trunk; (2) ataxia in gripping objects and in walking; (3) no ataxia observed. Muscle tone: (1) hypotonicity in upper limbs, fingers or face; (2) tonus according

432 ceased to be perceptible. Such results can to age; (3) rigidity of movements.

Chewing movements after raisins or biscuits had been put into the mouth: (1) no chewing, at most sucking; after a while raisins or biscuits fall out of the mouth; (2) slow, small and only episodical chewing movements with mouth open; (3) normal for age. Lips: (1) always parted; (2) mostly parted; (3) inconspicuous. Saliva: (1) hypersalivation; ( 2 ) sometimes hypersalivation; (3) no salivation observed. Speech sounds: (1) no speech, at most inarticulate sounds; (2) syllable-like utterances; (3) syllables, words, sentences or echolalia. Gait: (1) not possible; (2) rocking gait; (3) other types of gait or inconspicuous gait. Stance (with or without support under the armpits): (1) always broad-based; (2) sometimes broad-based; (3) never broad- based. Thumbs (left and right checked separately): (1) always adducted; (2) adducted only when grasping; (3) no adduction. Pronation of forearms (left and right checked separately): (1) always pronation; (2) pronation only when reaching for objects; (3) no pronation. Flexion of upper limbs: (1) at least one hand mostly in front of chest or chin; (2) upper limbs flexed in front of chest, at least when the child is in standing position (with or without support under the armpits); (3) normal flexion. Repertoire of movements: (1) extremely small, i.e. at most some stereotypies and turning of the head; (2) a small number of spontaneous movements or reactions to the stimulus situations and monotonous stereotypies; (3) large repertoire-also of stereotypic movements.

Results A number of behavioural traits were common to some children in all three goups of patients (e.g. hyperpnoea through the nose) and therefore will not be considered further. However, some behavioural patterns could be collected into three distinct groups as follows:

Observed in some cases of Rett syndrome but in none of the children with Kanner syndrome 0 Performances that correspond at best

to the third stage of ‘sensorimotor intelligence’.

N 0 Non-autistic and social behaviour; d

when some children with Rett syndrome

examiner), they approached them with a smile or laughing and with long-lasting eye-contact (Fig. l ) , sometimes together with signs of excitement such as hyper- ventilation. 0 In age-groups I and 11: when the child was helped to stand upright by being supported under the armpits she put her hands together in the midline in front of the chest or chin and had a broad-based stance. 0 In age-groups I, I1 and 111: children had uniform and monotonous stereotypic movements of the hands, which were held together in front of the chest or chin, a broad-based stance (Fig. 1) and laterally ambling gait. They had a very restricted repertoire of movements, without variation in form or speed; the movements are at most moderately fast. Stereotypic ‘hand-washing’ movements, with the arms flexed in front of the chest or chin (Fig. 2). Stereotypic wetting of the hands with saliva; either the child puts her fingers or hand deep into her mouth (Fig 3.) or the wetting coincides with the ‘hand-washing’ stereotypies. 0 In age-groups I1 and 111: Stereotypic bringing together of the hands in front of the chest or chin (Figs. 1, 4 and 9, with at most moderately fast movements and without additional movements of the upper extremities. 0 In age-group IV: Consistent, mono- tonous, isolated stretching and flexing of one or more fingers of one hand, i.e. long-lasting, at most moderately fast movements of the fingers without accomplished opposition of the thumb and without additional movements of the arms. Akinesia and amimia with at least one arm flexed in front of or lateral to the chest or stomach, with isolated, monotonous flexions of the fingers of one hand. 0 In age-groups 111 and IV: Slow movements only and at most a few spontaneous movements (‘hypoactivity’), with amimia or hypomimia apart from some of the characteristic stereotypies. 0 No chewing after raisins of biscuits had

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Fig. 1. Patient, age-group 11: note smile and eye- contact, broad-based stance. hands held together in front of chest.

Fig. 2. Patient, age-group IV: presenting stereotypic ‘hand- washing’ movements with arms flexed in front of chest.

Fig. 3. Patient, age-group I: putting fingers into mouth, wetting them with saliva.

Fig. 4. Patient, age-group 11: looks at spinning top but does not try to grasp it.

Fig. 5. Patient, age-group II: as examiner, seated on her left-hand side, rings bell on opposite side of her head, she maintains blank expression, with eyes open but apparently staring ‘through’ him.

Fig. 1.

Fig. 2.

Fig. 4.

Fig. 3.

Fig. 5.

been put into the mouth; there were either only sucking movements or the raisins or biscuits stayed on the tongue for a while and then fell out of the open mouth.

Observed in all cases of Rett syndrome but not in all cases of autistic syndrome c‘ Performances that correspond at most to the fourth stage of ‘sensorimotor intelligence’. Outside the stimulus situ- ations some children had shown accomplishments corresponding to the fifth stage, but had lost them very soon after training had stopped; they do not appear to have the capacity to transfer or generalise accomplishments corresponding to the fifth stage. C At most two words, no clauses (although in one case the parents told us that when she was at home their nine- year-old daughter sometimes spon- taneously said some words that she had learned when she was two years old, although she did not seem to use them purposefully). 0 No predominance of ‘social defence reactions’: touching the cheek and eye- contact more often yield reciprocation of the contact with a smile or by maintaining eye-contact, or else no visible response. C, Time spent looking at objects and people was at least as long as the time taken to manipulate objects. Some patients only looked at objects and did not grasp them (Fig. 4). C All children in age-group I had abducted thighs while sitting. When they were helped to stand upright by being supported under the armpits, they had a broad-based stance with arms flexed in front of the chest and hands in the midline in front of the chest or chin, with no motoric hyperactivity. (This is a very good test for Rett syndrome for children in age-group I.) i, In all age-groups the children episodically hold at least one arm flexed in front of or lateral to the chest or chin. C No self-injury activities; children with Rett syndrome did not pull their hair, knock themselves on the head or engage in any other activities likely to cause immediate pain. Some children with Rett syndrome had wounds on their hands or fingers that resulted from long-lasting stereotypies such as ‘hand-washing’ or

9 wetting their hands with saliva w (‘secondary self-injuring activities’).

0 Patterns of posture and movements of the arms that are associated with 2 dysfunction or developmental retardation 00 of the pyramidal tracts. All girls showed at least a tendency to adduct the thumb or 6 pronate the forearm in at least one arm. In age-groups I and I1 the children showed many individual differences in this respect (as they did in basic motor

behavioural traits). In age-groups 111 and IV these patterns were distinct (Fig. 1). In age-group I muscle tonus in the arms was very poor. 0 Ataxia: truncal ataxia of gait and ataxic patterns in reaching for and grasping objects. 0 There is great individual variation in Rett syndrome in the children’s basic motor development (just as there is in their autistic traits and in the pathological patterns of postures and movements associated with pyramidal tract dys- function), although all the girls had general retardation of their basic motor development. Some girls with Rett syndrome could walk swiftly and independently but none could run without symptoms of ataxia; some could not walk without support and one girl (aged 22 months) could not stand at all. 0 No proper chewing after raisins or biscuits had been put into the mouth: either the children did not chew the food at all and eventually it fell out of their open mouths, or chewing was only rudimentary and episodic with small and slow chewing movements with the lips slightly parted.

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Observed in most cases of Rett syndrome and therefore characteristic, but also in some cases of infantile autism I-) Children with Rett syndrome often turn their heads slowly horizontally and seem to look into the distance or at distant people at least as frequently as they look at their own bodies or at objects within reach. When looking at the examiner’s face from a near distance their eyes do not appear to be well accommodated and they seem to look through the examiner (Fig. 5 ) . They often show amimia or a blank expression, sometimes with a hint of a 435

smile, their eyes (bright) open (Figs. 1, 3 and 5); this applies also when they look at people’s faces. 0 In age-group I: teethgrinding. 0 Episodic hyperventilation through the mouth, simultaneous with symptoms of truncal ataxia, or episodic deep inhalation through the mouth with retention of air, followed either by swallowing or by audible (explosive) exhalation of air through the mouth only. 0 Broad-based stance and gait and apraxic gait. 0 No proper opposition of the thumb; at most opposition between the thumb and the side of the forefinger or only fist grip; no accomplished grasping.

Discussion Some of the present results differed from those reported in our earlier study (Olsson and Rett 1985). One girl with Rett syndrome once gripped a biscuit with her preferred left hand, with proper opposition of the thumb. Also, in some cases of infantile autism with brain damage, hyperpnoea through the mouth only was observed.

Among the children with Rett syndrome there were very small individual differences in sensorimotor performance in the stimulus situations. The levels of performance seem to be independent of the strong differences in their basic motor development. We were struck by the fact that children who could walk indepen- dently did not use their hands for purposeful gripping more often or more skilfully than the other girls.

We have pointed out that the visuomotor performances of children with Rett syndrome above the age of 22 months correspond at most to those of normal children between seven and 10 months old. There were some behavioural abnormalities similar to symptoms of severe dementia (as in Alzheimer’s disease), such as: a restricted repertoire of mental and motor performances, monotonous in form and speed; a small number of stereotypic movements that are also monotonous in form and speed; low responsiveness to the social environment; and ‘amimia’.

However. we cannot conclude that the 436 mental ages of children with Rett

syndrome are as low as four to 10 months in all respects. To what extent are their poor visuomotor accomplishments and loss of purposeful hand-use due to apraxia? Luria (1966) defined a form of apraxia caused by damage to the prefrontal area of the cerebrum. Patients with such damage can barely initiate and cannot fulfill purposeful activities. In the study by Nomura et al. (1984), the results of CT scans of Rett syndrome patients suggest an atrophic brainstem and volume loss of the thalamus and medial aspects of the frontal lobe in some children. These findings might reflect a lesion of brainstem nuclei and their projections. Non-specific corticomedullary atrophy and sclerotic-appearing sulci, similar to those seen in Alzheimer’s disease, might indicate that diffuse change occurs at a later stage of the disease. It is suggested that the age-related progression of motor and behavioural symptoms is associated with significant changes in the neostriatum and the mesolimbic system, with broader cortical involvement, predominantly of the frontal lobe (Nomura et al. 1984). Therefore the poor visuomotor accomplishments and loss of purposeful hand-use could be considered symptoms of apraxia and not just the results of severe intellectual retardation and autistic traits.

The autistic behavioural traits observed in the girls with Rett syndrome were not associated with their basic motor development. So to what extent is the infantile autistic syndrome, according to the 14 criteria listed in Table I , found in Rett syndrome patients over the age of 22 months?

There were individual differences in the autistic traits numbered 1, 2, 5, 8 and 10; these differences were more pronounced in the children in age-group I than in the older girls. Some of the girls did not show any friendly reactions (e.g. smiling at the examiner and inclining the head) in response to stroking their cheek, seeking eye-contact or calling their name. Two of them and only one of the older children (in age-group IV) sometimes rejected caressing and tenderness, i.e. turning away quickly and avoiding eye-contact. However, some children in each age- group seemed to enjoy social contact

more than anything else. Seeing the examiner, they started smiling or sought eye-contact. They seemed more happy when they were near people. In contrast to the children with the autistic syndrome, they also looked at different objects-not only at one special object-for a long time. Therefore, points 1, 2, 5 , 8 and 10 were not found to the same extent or in the same form in the children with Rett syndrome as in those with autism, in spite of individual differences. Most of them were passive and did not put up any resistance. They responded strongly to loud noises and always showed particular interest in the sound of rustling paper out of their sight.

Neither do points 3, 4, 6, 11, 12 and 13 apply to the same extent and in the same form to the girls with Rett syndrome. When similar traits were observed they appeared to be the result of severe developmental retardation. In contrast to the children with the autistic syndrome, the girls with Rett syndrome presented a kind of behaviour that corresponded at most to the fourth stage of ‘sensorimotor intelligence’, and in many cases to the third stage only.

Almost all children with Rett syndrome like to crumple up bits of paper, but some do so only if the paper is put directly into their hands while they are engaged in the characteristic hand-washing movements. Crumpling paper was the only stereotypic playing with objects that we found in Rett syndrome. We do not regard this behaviour as the same as that of children with the autistic syndrome who, for instance, rotate small objects or sway them between their fingers or otherwise manipulate them for a long time. For these children (particularly those with Kanner syndrome) the tactile and proprioceptive stimuli of fast movements with the fingers and hands and, for short moments, visual impressions of fast- moving objects, seem to be the most important feedback for keeping up the characteristic stereotypic playing habits with objects for long periods. However, it is the noise the paper makes when it is crumpled which seems to provide the feedback for children with Rett syndrome. They do it repeatedly, but are unable to maintain this manipulation for

long because the paper soon falls out of their hands. Some children with Rett syndrome grasped bits of paper before they heard the noise of crumpling, 6 showing that they already knew the 00

acoustic quality of paper. This 2 accomplishment does not necessarily d

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$ developed to the fifth stage of ‘sensorimotor intelligence’; it may also be a result of long-term experience with 9 paper. We believe that it is not necessary is to have attained even the fourth stage to $ these reactions are very similar to 3 ‘secondary circular reactions’ in the third $

B B

u .r have such reactions to paper; indeed,

- - stage of ‘sensorimotor intelligence’. Between the ages of four and six months the normal child develops eye-hand co- ordination and other signs of intermodal

activities, obviously with a purpose and with enjoyment, e.g. the child repeatedly strikes a rattle and pays close attention to the resulting noise (Piaget 1952).

Children with Rett syndrome looked at objects longer than they held them in their hands and in some cases grasped objects without proper opposition of the thumb, in most cases only with a fist grip. In contrast, the performance of all patients with Kanner syndrome corresponded to a higher level of ‘sensorimotor intelligence’. Despite this, however, they showed little purposeful action with objects. To give an example: children with Kanner syndrome looked at objects very briefly; having grasped an object, they would handle it without regard to its specific function (except for the top), and did so for a longer time than they spent looking at it. They grasped and handled objects quickly and skilfully with their fingertips. They showed proper opposition of the thumb (with stable and mostly good tone in the fingers). They also showed a complex repertoire of movements and postures; movements which differed in speed and form followed each other in quick succession. These features were also found in the stereotypic movements of the children with brain-damage-related autism. It is from this combination of motor accomplishments on the one hand and the purposeless use of space, objects and social environment on the other that

E 2

integrations and begins to repeat relevant

43 7

the behavioural features which charac- terise the Kanner syndrome most clearly arise.

Finally, points 7, 9 and 14 in Table I do not apply to Rett syndrome in the same way as they do to the autistic syndrome.

Like autistic children, children with Rett syndrome sometimes smiled to themselves without a recognisable cause. However, unlike the autistic children, in doing so they would shift their gaze with a slow horizontal turn of the head and would seem to look vaguely about rather than focusing on any near object, whereas the children with Kanner syndrome focused their eyes only on a limited space or on close objects.

Most children with Rett syndrome smiled at people’s faces, looking in the direction of their eyes. However, they did not really fix on and accommodate to faces or eyes, thus giving the impression that they were looking through the person. It was striking that they smiled with about the same frequency at unfamiliar people in an unfamiliar room as they did when looking at their mother or father; it was a kind of ‘social smile’. The girls with Rett syndrome therefore impressed us as being highly retarded in their social and affective development. The over-all picture is of almost global severe mental and affective retardation.

Children with Rett syndrome were physically hyperactive but only within the confines of a very restricted repertoire of postures and movements. Within this restricted repertoire, their hyperactivity and stereotypic movements were monotonous in form and speed. We suggest that these features belong to their general and severe mental and motor retardation. In other words, they did not show such variety and fast changes of movements and postures as did the patients with the autistic syndrome.

Like children with the autistic syndrome, patients with Rett syndrome appear isolated, particularly as they grow older. In contrast to the autistic syndrome, however, their isolation is the result of their severe developmental retardation. Their social interaction corresponds largely to the mental age of their behaviour in general.

438 As described, children with Rett

syndrome showed only secondary, rather than primary, self-injuring activities, probably because they are too mentally and motor-retarded to do so.

Hence, since we have failed to fulfill the precondition of at least seven points from the table of criteria for autism, we can conclude that children with Rett syn- drome over the age of 22 months do not have the infantile autistic syndrome. If the behaviour of patients is carefully analysed, some characteristic differences in the 14 criteria will be found between the syndromes, as well as behaviour that can be recorded in Rett syndrome but not in the autistic syndrome. Autistic-like be- haviour observed in patients with Rett syndrome in age-group I can be interpreted mainly as a consequence of severe general mental, emotional and motor retardation. Therefore we concur with Rolando (1985) in calling such behavioural traits ‘pseudo-autistic abnormalities’.

As yet we can only speculate as to the causes of the characteristic ‘hand- washing’ stereotypies in Rett syndrome. According to Piaget (1952), the starting- points of ‘sensorimotor intelligence’ in the first year of life are the innate reflexes and more or less complicated automatisms. The simplest and earliest form of cognition is the registering of the trigger stimulus. In the second stage of ‘sensorimotor intelligence’ the reflexes and automatisms are repeated by the child, e.g. they engage in sucking movements with the mouth even while they are lying satisfied in their cot. Piaget called repeated movements without visible trigger stimuli ‘primary circular reactions’. We know today that simple and also complicated automatisms can be elicited by stimulation of parts of the brainstem and basal ganglia. The evaluation by Nomura et al. (1984) of the pathophysiology of Rett syndrome suggested the initial lesion to be in the RaphC nuclei and other parts of the brainstem, with late progressive involvement of other parts of the higher CNS. There is a progressive mental retardation in the second half of the first year of life; after the first birthday there is a short period of deterioration (Rolando 1985, Kerr and Stephenson

1985); and the performances of patients older than 22 months correspond at most to those of normal children aged 11 months (Olsson and Rett 1985). Perhaps these anomalies are due partly to apraxia resulting from early disturbance of brainstem functions. We conclude that ‘hand-washing’ stereotypies are the repeatedly elicited traces of purposeful hand movements which occur within the framework of mental and motor regression and early and progressive lesions in the brainstem nuclei and which, because of severe mental and motor retardation, cannot be stopped, running their course as ‘primary circular reactions’.

The presence of neurological signs, the inability to organise purposeful activities (which is true apraxia) and the poverty of the stereotypies differentiate the Rett syndrome from autism, in which elaborate behaviour or actions are possible (Roland0 1985). Because of the pseudo-autistic abnormalities and because of autistic traits which differ individually between the younger children, we agree with the recommendation of Kerr and

7 Stephenson (1985) that Rett syndrome should be considered whenever girls are 3 referred with a diagnosis of autism.

A more widespread knowledge of Rett 6 syndrome is necessary in order to reduce the troublesome and time-consuming 5 series of investigations to which these s patients are usually submitted, to allay any sense of guilt that might be felt by their parents and to allow realistic and clear suggestions to be made regarding

*

r= m

s e

2 8

adaptive and therapeutic programmes. 5, 3 $. s!

Accepted for publication 17th September 1986.

Ackno wledgements .z

We are grateful to Dr. Christiane Rembart for her assistance in the observational phase of the study and to Dr. Christa Cihak for the photographs. We

c s t also thank Mag. Barbara Olsson for the translation

into English.

Authors’ Appointments *Bo Olsson, Ph.D., Psychologist; Andreas Rett, M.D., University Professor of Neurology, Head of the Ludwig Boltzmann Institute for Research on Brain Damage in Children.

*Correspondence to first author at Ludwig Boltzmann-Institut zur Erforschung kindlicher Hirnschaden, 1130 Wien, Riedelgasse 5 , Austria.

2

SUMMARY The most common wrong diagnosis of children with Rett syndrome has been the infantile autistic syndrome, and it is probable that this false diagnosis continues to be made in many places. This paper is a follow-up to the authors’ previous study concerning differential diagnosis between the two syndromes and is based on the observation of 63 patients over the age of 22 months in 10 stimulus situations.

In Rett syndrome there were very small individual differences in the sensorimotor performances, which correspond only to the third and fourth stages of Piaget’s ‘sensorimotor intelligence’ scale. There were pronounced individual differences in the levels of basic motor development and, independently from these, in autistic behavioural traits. When the children’s behaviour was examined in detail, it became evident that girls with Rett syndrome differ in many subtle ways from those with the autistic syndrome. Behaviour observed in some cases of Rett syndrome but in none of the autistic syndrome included: social (non-autistic) behaviour; no chewing, at most sucking of items of food placed in the mouth; monotonous ‘hand-washing’ movements with arms flexed in front of chest or chin. In all cases of Rett syndrome but in only some of the autistic syndrome there were: no ‘social defence reactions’ nor ‘primary self-injuring activities’; some form of ataxia and a very restricted repertoire of postures and movements, monotonous in form and speed; and the time spent looking at objects and people was at least as long as the time taken to manipulate objects.

Some causes of the characteristic stereotypic hand movements observed in Rett syndrome are also suggested.

RCSUMC Autisme et syndrome de Rett: analyses comportementales et diagnostic diffPrentiel L’erreur de diagnostic la plus frequente chez les enfants presentant un syndrome de Rett a ete le syndrome d’autisme infantile et il est probable que ce faux diagnostic continue a &re souvent porte. Cet article est un suivi aux etudes anterieures des auteurs concernant le diagnostic differentiel entre les deux syndromes et est base sur I’observation de 63 patients au d e b de I’lge de 22 mois dans dix situations de stimulus. Dans le syndrome de Rett, il y a tres peu de differences individuelles dans les performances sensorimotrices correspondant seulement aux troisieme et quatrieme etapes de 1’Cchelle d’intelligence sensorimotrice de Piaget. I1 y avait des differences individuelles dans le niveau du devcloppement moteur de base et de facon independante dans les traits de comportement autistique. Quand le comportement des enfants a ete examine en detail, i l est devenu evident que les filles atteintes de syndrome de Rett different de nombreuses facons de celles qui presentent un syndrome autistique. Le comportement observe dans guelques cas de syndrome de Rett, mais dans aucun cas 439

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de syndrome autistique incluait: un comportement social (non autistique); pas de michonnement, au plus succion de parties de nourriture placies dans la bouche; mouvements monotones de ‘lavage dc mains’ avec les bras flechis devant la poitrine ou le menton. Dns tous les cas de syndrome de Rett et seulement dans certains cas de syndromes autistiques, on notait: pas de reaction sociale de defense’ ni d“activite’ d’auto-mutilation primaire’; un certain degrk d’ataxie et un repertoire restreint de postures et de mouvements, monotones dans la forme et la vitesse; le temps passe B regarder les objets et les persondes ktait au moins aussi long que le temps passe B manipuler les objets. Quelques causes de mouvements de mains stereotypes, caracteristiques, observes dans le syndrome de Rett sont suggerees.

ZUSAMMENFASSUNG Autismus und Rett Syndrom: Untersuchungen des Verhaltens und Differentialdiagnose Die haufigste Fehldiagnose bei Kindern mit Rett Syndrom ist das infantile Autismus Syndrom, und wahrscheinlich wird diese Fehldiagnose weiterhin an vielen Orten gestellt. Diese Arbeit ist eine Weiterfuhrung der fruheren Studie der Autoren und befant sich mit der Differentialdiagnose der beiden Syndrome; sie stiitzt sich auf die Beobachtungen von 63 Patienten in 10 Testsituationen, die alter als 22 Monate waren. Beim Rett Syndrom fanden sich nur sehr geringe individuelle Unterschiede bei den sensomotorischen Leistungen, die nur der dritten und vierten Stufe der Skala fur ‘sensomotorische Intelligenz’ nach Piaget entsprachen. Es gab deutliche individuelle Unterschiede bei der allgemeinen motorischen Entwicklung und unabhangig davon bei den autistischen Verhaltensweisen. Wenn man das Verhalten der Kinder im Einzelnen untersuchte, so stellte sich heraus, dan sich Mldchen mit Rett Syndrom in vielen subtilen Punkten von denen mit einem autistischen Syndrom unterscheiden. Folgende Verhaltensweisen wurden in einigen Fallen mit Rett Syndrom, jedoch in keinem Fall mit autistischem Syndrom beobachtet: soziales (nicht autistisches) Verhalten; kein Kauen, allenfalls Saugen der in den Mund gebrachten Nahrungsbestandteile; monotone ‘Hand-wasch’ Bewegungen, wobei die Arme vor die Brust oder das Kinn gehalten wurden. In allen Fallen mit Rett Syndrom, jedoch nur in einigen mit autistischem Syndrom fanden sich: keine ‘sozialen Verteidigungsreaktionen’, noch primar selbstverletzende Handlungen’; eine gewisse Form der Ataxie und und ein sehr begrenztes Repertoire von Haltungen und Bewegungen, die in monotoner Art und Geschwindigkeit abliefen; und die Zeit, die damit verbracht wurde, Gegenstande und Leute anzusehen, war mindestens so lang wie die Zeit, in der Gegenstande befiihlt wurden. Es werden noch einige Ursachen fur charakteristische, stereotype Handbewegungen beschrieben, die beim Rett Syndrom beobachtet worden sind.

RESUMEN Autism0 y sindrome de Rett; investigaciones conductuales y diagndstico diferencial El diagnbstico equivocado m8s corriente en niflos con sindrome de Rett es el de autism0 infantil y es probable que este falso diagn6stico se continue haciendo en muchos lugares. Este escrito versa sobre el seguimiento de un estudio hecho previamente por 10s autores, concerniendo a1 diagndstico diferencial entre 10s dos sindromes y se basa en la observaci6n de 63 pacientes de m8s de 22 meses de edad en 10 situaciones de estimulo. En el sindrome de Rett habia unas diferencias individuales muy pequeflas en la realizacibn sensoriomotora, que correspondia s610 a1 tercer y cuarto estadios de Piaget en su escala de ‘inteligencia sensoriomotora’. Habian unas diferencias individuales marcadas en 10s niveles del desarrollo motor basic0 y, con independencia de ellos, en 10s rasgos conductuales autisticos. Cuando el comportamiento del niflo se examinaba en detalle, se hacia evidente que las niflas con sindrome de Rett diferian, en multiples detales sutiles, de las que no sufrian el sindrome de Rett. El comportamiento observado en algunos casos de sindrome de Rett i en ningun autistico incluyen: comportamiento social (no autistico); no masticaci6n, o como m b i m o chupeteo, en 10s items en que se les colocaba un aliment0 en la boca; movimientos mon6tonos de ‘lavarse las manos’, con 10s brazos flexionados delante del pecho el mentbn. En todos 10s casos de sindrome de Rett y s610 en alguno con sindrome autista habia: reacciones de ‘defensa local’ ‘actividades primarias de autoagresion’; alguna forma de ataxia y un repertorio muy restringido de posturas y movimientos, mon6tonos en su forma y rapidez; y el tiempo pasado mirando a objetos y gente era por lo menos tan largo como el que pasaba manipulando objetos. Se sugieren tambien algunas de la causas de 10s movimientos estereotipados de manos observados en el sindrome de Rett.

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