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Delayed Visual Maturation and Autism

Robert Goodman Lesley Ashby

Just as some children are slow to walk or talk, others seem slow to see, being visually unresponsive early in life and only subsequently developing visual interest and competence. Illingworth (1961) coined the term 'delayed visual maturation' (DVM) to describe two such children, and the label has since been widely adopted. As a diagnostic label, DVM may be used in either a broad or a narrow sense. In its broad sense, DVM traditionally has been used to refer to any apparently blind infant who subsequently sees, irrespective of coexistent neuro- developmental or ocular abnormalities (Fielder et al. 1985). More recently, Lambert et al. (1989) have suggested a narrower definition, to exclude infants with evidence of neurological insults or additional ocular abnormalities. In this paper, DVM is used in its original, broader sense.

It is characteristic of DVM that visual responsiveness emerges before the age of six months in children of normal intelligence, and somewhat later in children with general developmental delay (Fielder et al. 1985). Although many infants with DVM appear to develop normally, apart from their slowness to see, follow-up studies of these children have shown a high rate of associated developmental problems, including gen- eral developmental delay and specific speech or language delay (Cole et al. 1984, Fielder et al. 1985, Lambert et al. 1989). A link between DVM and a pervasive developmental disorder such as infantile autism has not been described previously.

The behaviour of young autistic children often involves an idiosyncratic mixture of hyper- and hyporesponsiveness to sensory stimuli (Ornitz 1985). An

autistic child's lack of interest in sound often leads parents to suspect a hearing problem (Rutter et al. 1967), and this concern about deafness is commonly the presenting complaint when the child is first brought to medical attention. Autistic children may also show abnormal visual responsiveness, e.g. looking with interest at some inanimate objects while ignoring people (Schopler 1965), but this selective visual interest is unlikely to be mistaken for blindness. We are not aware of any reports of autistic children who first came to medical attention because of a transient global lack of visual responsiveness.

We report here three boys who first presented with slowness to see, and who subsequently manifested severe autistic impairment. In the two older boys, resolution of the autistic symptoms has been surprisingly good.

Case reports CASE 1 John is the third child of unrelated parents. One older brother has developed normally, but a second brother died in infancy with optic and cerebral atrophy of unknown aetiology. Pregnancy and birth were uncomplicated. In early infancy John reacted to noise, but not to visual stimuli. His parents thought him blind, and a paediatrician documented that fixing and following responses were absent at 10 weeks. Visual responsiveness emerged shortly before he was seen by a paediatric neurologist at six months, at which stage he had a convergent squint and mild rotatory nystagmus at rest. Visual improvement continued, his squint was surgically corrected, and there has been no recent concern about his vision. He navigates proficiently in unfamiliar surroundings, and notices tiny near-by objects.

John was moderately hypotonic as an infant. Motor milestones were markedly delayed: sitting alone from 15 months, crawling from 33 months and walking unaided from 46 months. At the age of 5 % , gross motor co-ordination was poor, but tone, power and tendon reflexes were normal.

Normal early cooing was succeeded by limited reduplicative babble which faded out in the second year. H e did not acquire any words or gestures, and showed no understanding of spoken or gestural communication. As an infant, he preferred being left in his cot to being picked up. Subsequently, episodes of screaming or severe head-banging were frequently precipitated by cuddles, eye-contact, or changes in routine. There was little or no selective attachment to his parents or brother. From 12 months of age he spent long periods stereotypically pushing objects to and fro, and he began lining toy cars up in rows from the age of 30 months. There was no constructive or symbolic play at this stage.

Improvements in communication and social

interaction were first noted at about 3 % years, when John started to babble again, began to follow simple commands, showed selective attachment to his mother and accepted cuddles. Severe head-banging continued, however, leading to a six-month admission to a child psychiatric unit. Head-banging was abolished by a behavioural approach, and an intensive programme of skill building was initiated. During his admission he advanced from having no formal means of expression to using two-word phrases in Makaton sign language.

When assessed at 5 % years, signing had largely been replaced by speech. John had an active vocabulary in excess of 100 words, which he used with normal inflection and supplemented with formal signs and informal gestures. He could comprehend two-part commands. He was spontaneously affectionate to his immediate family, to whom he also turned for comfort when hurt. He enjoyed playing in parallel with his brother and other children, and could take turns in games of chase. Head-banging had not recurred, and obsessional play and resistance to change were much less prominent. He enjoyed imaginative play, enacting simple scenes with miniature figures, and employing symbols flexibly (e.g. using a banana as a gun at one time and as a phone at another). Puzzles and form-boards were completed at a two- to three-year-old level. He appeared to be well placed at a school for children with severe learning disabilities.

CASE 2 After an uncomplicated pregnancy, Henry was born at term with the cord round his neck, and required a brief period of resuscitation. He was subsequently noted to have various dysmorphic features, including low-set ears, a small chin, a low hair-line, one undescended testis, and broad hands with clinodactyly. Weight and head circumference were normal at birth. Head circumference increased along the 50th percentile, whereas weight fell to the 3rd percentile and then tracked along it. Karyotype was normal and a paediatric geneticist could not diagnose a specific dysmorphic syndrome.

Henry's parents initially thought he was blind. At three months a paediatrician documented a marked lack of visual responsiveness, combined with a convergent squint and rotatory nystagmus. These findings were confirmed at four months by a paediatric ophthalmologist. Fixing and following became evident by seven months and the squint was surgically corrected at 12 months. From that age his vision was thought to be adequate for his current developmental needs. Visual acuity a t four years was 6/18.

From the age of four months, Henry's mother and nanny embarked on a programme of intensive stimulation, using toys, social contact, music, physical activities and coaching for motor milestones. From the age of 2% years this was supplemented by speech therapy, home teaching and regular attendance at ordinary and special playgroups.

Henry was hypotonic as an infant. He sat alone and crawled from 13 months, and walked alone from 18 months. His gait has remained clumsy and awkward.

As an infant, he did not seek or respond to adult attention, preferring to be left alone in his cot. Gaze avoidance was obvious by 12 months. He particularly withdrew from children and unfamiliar adults. His social interactions with familiar adults were limited and used primarily as means to non- social ends. He did not use gestures before the age of three years, up to which time he indicated his wants by tugging adults toward desired objects, neither pointing nor making eye-contact. Although he had acquired six words with meaning by the age of two years, speech during the third year was largely restricted to immediate and delayed echoing. Comprehension was poor, articulation indistinct, and intonation high-pitched and monotonous. Stereotyped behaviours and dislike of change were evident from 12 months onwards. He had no symbolic play. At 22 months his nonverbal cognitive level was assessed at less than 12 months.

When last assessed, aged four years, Henry was strongly attached to his mother and enjoyed cuddles. He liked the company of children, sometimes making social overtures and engaging in parallel play and in simple co-operative and turn-taking play. Eye-contact was greatly improved, and his gestural repertoire included pointing, waving and raising his arms to be picked up. Verbal comprehension included two-part commands and his spoken vocabulary was extensive, though speech was primarily instrumental rather than chatty. He had a large reading vocabulary and a great liking for flash-cards and books. In play he used cuddly animals and miniature toys to enact simple everyday events. Rigidity had decreased and he only occasionally reverted to stereotyped play. His Griffiths developmental quotient was 69 over-all (80 on performance scale), and his reading and number skills were six to 12 months in advance of his chronological age.

CASE 3 Following a normal pregnancy, Nicholas was born at term by elective caesarean section for cephalopelvic disproportion. His parents thought him blind, and a lack of visual responsiveness was repeatedly documented by paediatricians and ophthalmologists throughout his first year. At 14 months, when fixing and following responses were definitely present, ocular motor apraxia was suspected because of Nicholas's reliance on head movements to shift his gaze from one object to another. The ocular motor apraxia was still evident when he was last assessed, aged three years. At that time his vision was sufficient to enable him to navigate proficiently in unfamiliar surroundings, to recognise distant objects and to follow a lcm ball at 4.5 metres.

CT and MRI scans demonstrated partial absence of the septum pellucidum, but no other abnormalities. A diagnosis of septo-optic dysplasia was considered, but dismissed in view of Nicholas's normal optic discs, optic nerves and visual evoked responses.

Marked hypotonia and poor head control were noted in early infancy. He sat alone from nine months and walked independently from 24 months. Gross and fine motor co-ordination were poor at three years.

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TABLE I Comparison of cases

Initially referred for ?blindness Fundoscopy normal ERG and VER normal CT and MRI normal Associated convergent squint Age visual improvement noted (mths) Ocular motor apraxia Hypotonic as an infant Delayed motor milestones Persistent clumsiness Autistic social impairment Autistic impairment in communication Rigidity and repetitive behaviours Age at last follow-up (yrs) Unexpectedly good outcome

Case I Case 2 Case 3

+ + + + + 5 -

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+ + + + + 7

+ + + + + + 3 +

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14 + + + + + + -

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Nicholas was a very passive baby; he did not nestle when held and resisted being cuddled closely. During his second year he showed little interest in people and did not appear to be selectively attached to his parents. Early cooing was followed by simple babble, which faded out completely by 18 months and re-emerged at the end of the second year. At that stage he did not understand any speech and made no use of gesturing. He did not spontaneously engage in any sort of play, appearing content to d o nothing for long periods.

By 2% years he understood at least 15 single words and he used jargon babble with speech-like inflexions. He was selectively attached to his nanny, following her around the house. He sometimes approached his mother for cuddles, and began imitating his older sister and attempting to play alongside her. When alone, his favourite pastimes were opening and shutting doors and carrying objects from one room to another. He flapped his hands when he was upset and would sometimes bite his own hand when frustrated.

Aged three years, Nicholas was echoing more and had at least six definite words which he used appropriately. He could wave ‘bye-bye’ and raise his arms to be picked up, but did not point, instead tugging people when he needed their help to obtain something he wanted. He actively sought comfort from his parents when hurt, and he particularly enjoyed the company of his sister, appearing to miss her when she was at school. He imitated actions he had seen (watering the garden, setting the table) and he had a teddy-bear he liked to cuddle, push in a toy pram and put to bed. He enjoyed sitting on his parents’ laps while being shown pictures in books. He could do simple form-boards and puzzles with prompting, but not unaided.

Discussion As summarised in the Table I, all three cases have many features in common, cases 1 and 2 being particularly similar. All three boys seemed blind in early

infancy and only subsequently acquired visual responsiveness. For cases 1 and 2, this slowness to see can be classified as DVM, in the broad sense. It is harder to classify case 3’s slowness to see, given the ocular motor apraxia that was first noted in his second year. The original description of congenital ocular motor apraxia by Cogan (1953) included two children who were thought to be blind by their parents. In both instances, however, visual responsiveness was apparent by six months, accompanied by the head-jerking movements that are characteristic of this disorder. In our case 3, by contrast, no head-jerking movements were noted until 14 months, despite repeated assess- ments by a paediatric ophthalmologist, a paediatric neurologist, and a develop- mental paediatrician with a special interest in visual disability. We are reluctant, therefore, to accept that his apparent slowness to see was entirely attributable to ocular motor difficulties. Perhaps he was affected by both DVM and congenital ocular motor apraxia, with the former initially masking the latter.

Cases 1 and 2 fulfil clinical and research operational diagnostic criteria for autism (American Psychiatric Association 1987, Bryson er al. 1988). Case 3 manifests the Wing and Could (1979) autistic ‘triad’ of impairments in social recognition, com- munication and play, though the absence of rigidity and the paucity of repetitive behaviour precludes a diagnosis of

autism according to most, but not all, classificatory systems (see Denckla 1986, Cohen et al. 1987).

While we cannot rule out the possibility that the combination of DVM and an autistic disorder was simply a coincidence in our cases, this seems improbable since both conditions are rare. Austistic disorders, in the broadest sense, affect roughly two children per thousand (Wing and Gould 1979). DVM is probably substantially rarer than this, though exact prevalence data are lacking.

A true association between DVM and autistic disorders could reflect one of three types of causal link. The first is that DVM may cause subsequent autistic impairments, but there are no previous reports of DVM being followed by an autistic disorder, and the rate of autistic syndromes is relatively low, even among individuals with unremitting congenital blindness (Jan et al. 1977). Although some autistic features, such as stereo- typies, echolalia and pronominal reversal, are common among congenitally blind children (Fraiberg 1977), they are generally mild or transient and do not add up to the severe autistic syndrome seen in our cases. While early visual problems clearly are not a sufficient cause of severe autistic impairments, they may be contributory causes in predisposed individuals.

Alternatively, the second causal link might run in the opposite direction, with autism producing early visual unrespon- siveness. As noted earlier, however, the type of visual unresponsiveness previously described in autism is generally more suggestive of a lack of interest in looking at people than of DVM. It is worth noting, however, that the combination of DVM and autism may have gone unreported previously because retrospective accounts of DVM in autistic children could easily be misattributed to early deficits in social interest.

The third explanation for the co- occurrence of DVM and autism is that both conditions may sometimes arise from a single underlying pathology, in much the same way that autism and permanent visual impairment can both result from congenital rubella (Chess 1971).

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Developmental progress has been surprisingly good for cases 1 and 2, given the severity of each boy's autistic m

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advances in social interaction, language Q' and imaginative play are very striking, as 5 are the decreases in rigidity and repetitive 2

2 progress has been unusually good, though not unprecedentedly so, is in keeping with 2 the limited available data on the natural 3 history of autism (see Rutter 1978). Good 2 prognostic factors for future progress oi

.E include the early acquisition of useful 2 speech (Rutter 1978), the presence of clumsiness (Rutter 1978), and, for case 2 only, advanced reading skills (Burd et af. 19876). Since case 3 was only three years old when last assessed, it is too early to judge the quality of his outcome, though recent progress has been encouraging.

If our preliminary findings are confirmed by longer follow-up of larger numbers of cases, a history of DVM will join the short list of additional disabilities that confer a better prognosis on autistic children-other instances being clum- siness (Rutter 1978) and Tourette syndrome (Burd et al. 1987a). An unexpectedly good prognosis has also been described for autism associated with congenital rubella (Chess 1977). It is interesting to note that a history of profound unresponsiveness to sound is a bad prognostic feature in autism, perhaps because it is associated with particularly severe language disorder (Rutter et al. 1967).

One possibility why a history of DVM might be associated with an unusually good resolution of autistic impairment is that visual improvement also triggers off improvements in other areas. If the social and communicative barriers imposed by blindness can amplify a relatively mild predisposition to autism, it is plausible that subsequent resolution of the blind- ness could lead to marked improvement in autistic symptoms. If this explanation were correct, however, it is not easy to see why the marked improvement in the autistic symptoms of case 1 did not occur until three years after the resolution of blindness. Perhaps the combination of early blindness and constitutional 817

grown these impairments, but the

behaviour. Our clinical impression that $

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vulnerability sets an individual onto an abnormal developmental course, which tends to persist unless visual improvement is combined with the type of intensive skill building programme that began in the fourth year of life for case 1 , and in the first year of life for case 2.

An alternative explanation for the association between DVM and autism with a good prognosis is that both disorders reflect widespread, though patchy, delays in brain maturation; these delays particularly affecting brain systems involved in visual perception, motor control, communication, and social interest and awareness. Since the rate of neuronal maturation varies between different brain regions (Goodman 1990), maturational abnormalities affecting the visual system may resolve sooner than related maturational abnormalities affect- ing language, play and social interaction. Although the notion of multifocal maturational delays is attractive, it is important to remember that delays in behavioural development do not necessarily reflect delays in neuronal development (Goodman 1990). Thus delayed neuronal maturation is not the only possible explanation for DVM. For

example, if the extra-geniculostriate system mediates visual responsiveness in young infants, with the geniculostriate system taking a more prominent rdle thereafter, then a permanent abnormality in the extra-geniculostriate system would result in transient blindness until geni- culostriate function emerged (Tressider et al. 1990). Improved understanding of the pathophysiology of DVM may also provide valuable clues to the patho- physiology of some autistic syndromes.

Accepted for publication 5th December 1989.

Acknowledgements The authors are grateful for the advice and encouragement received from Professors P. Graham, M. Rutter and A. Fielder, and from Drs. 1. Goodyer, M. Prendergast, A. Gath and A. Kriss. Particular thanks to Dr. M. Prendergast, who first drew the authors’ attention to case 1. During the preparation of this report, Robert Goodman was supported by a clinical research training fellowship funded by the Wellcome Trust.

Authors’ Appointments *Robert Goodman, Senior Lecturer, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, De Crespigny Park, London SES 8AF. (Formerly Research Fellow, Institute of Child Health, London.) Lesley Ashby, Clinical Lecturer, Department of Child Psychiatry, Cambridge.

*Correspondence to first author

SUMMARY Three boys are described with a mixed developmental disorder, which so far appears to have a relatively good prognosis. Each boy presented in early infancy with visual unresponsiveness, which spontaneously resolved. This delayed visual maturation was accompanied or followed by severe autistic impairment, general developmental delay, hypotonia and clumsiness. Subsequent progress has been unexpectedly favourable, with striking improvements in language, play, social interest and social competence. Widespread, patchy delay in brain maturation could possibly account for this combination of delayed visual maturation and autism, with a good prognosis.

RESUME Maturation visuelle retardee et autisme L’article decrit trois garcons presentant un desordre developpemental complexe, avec jusqu’a ce jour un relativement bon pronostic. Chaque garcon avait present6 durant la premiere enfance une absence de rtponse visuelle, ayant disparue spontanement par la suite. Ce retard de maturation visuelle s’accompagnait de troubles autistiques severes, d’un retard global de maturation, d’une hypotonie et d’une maladresse. Les progres ulterieurs ont ete favorables de faGon inattendue, avec une amelioration frappante du langage, du jeu, de I’interet et de la competence sociale. Un retard de maturation cerebrale, avec des localisations prkcises et en grand nombre, pourrait expliquer cette association de retard de maturation visuelle et d’autisme, avec bon pronostic.

ZUSAMMENFASSUNG Verzogerte visuelle Reifung und Autismus Es werden drei Jungen mit einer mehrschichtigen Entwicklungsstorung beschrieben, die, soweit man das bisher beurteilen kann, eine relativ gute Prognose zu haben scheint. Im fruhen Kindesalter zeigten die Jungen keine Reaktion auf visuelle Reize, was sich spontan anderte. Diese verzogerte visuelle Reifung war begleitet oder gefolgt von schweren autistischen Symptomen, allgemeinen Entwicklungsverzogerungen, Hypotonie und Ungeschicklichkeit. Der weitere Entwicklungsfortschritt war unerwartet gut, mit bemerkenswerten Besserungen in Sprache, Spiel, sozialen Interessen und sozialem Verhalten. Eine ausgedehnte fleckige Hirnreifungsverzogerung konnte die Ursache fur diese Kombination von verzogerter visueller Reifung und Autismus mit guter Prognose sein.

RESUMEN Retraso en la rnaduracion visual y autism0 Se describen tres niilos varones con una alteracion del desarrollo mixta, con un pronostico hasta el momento bueno. Cada niao habia tenido a1 inicio de su vida una falta de respuesta visual que se resolvio espontaneamente. Este retraso en la maduracion visual se acompail6 o siguio de alteracion autistica grave, retraso general en el desarrollo, hipotonia y torpeza. El curso posterior fue sorprendentemente favorable con marcada mejoria en el lenguaje, juego, interes social y competencia social. Una maduracion retrasada parcheada y extendida podria explicar esta combinacion de retraso en la maduracion visual y autismo, con un buen pronostico.

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