Clinical Neuroscience Research 6 (2006) 113117 www.elsevier.

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The clinical spectrum of autism

Abstract Autism, as dened by Kanner in 1943, required two features: the abnormal development of social relationships and the obsessive desire for the maintenance of sameness. This denition was applied only to children without dysmorphic features (except macrocephaly) and without profound mental retardation. This denition resulted in a strongly familial disorder. Family members of such cases have not only strictly dened autism but the milder Pervasive Developmental Disorder, Not Otherwise Specied (PDDNOS), and Asperger syndrome as well as milder social dysfunction, obsessional personality characteristics, language and reading disorders, and anxiety and depression. Some of these conditions have come to be called autism spectrum disorders. Family members of strictly dened autism cases do not tend to have mental retardation, even when the proband with autism may have marked cognitive impairment and limited language. Another group of children that often meet modern criteria for autism and PDDNOS are those with profound mental retardation (IQ < 35 or 40), children with dysmorphic facial features, specic genetic conditions, such as tuberous sclerosis or Retts syndrome, and children who have suered certain kinds of severe encephalitis at an early age. These children are etiologically very heterogeneous and need to be considered separately in studies of etiology and mechanism. 2006 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.
Keywords: Clinical features; Diagnosis; Autism spectrum

1. Leo Kanner Leo Kanner (18941981) was born in Austria and studied Literature at the University of Berlin. During World War I, he was trained as a medic in the army, and after the war he studied medicine, also at the University of Berlin. He received his Bachelor of Medicine (MB) in 1919, and completed his MD thesis in cardiology in 1920. He practiced in Berlin through 1923, when he immigrated to the United States, having obtained a position at Yankton State Hospital in South Dakota. He worked there until 1929, when he was accepted in the psychiatry residency in Adolph Meyers department at Johns Hopkins Hospital in Baltimore. He became interested in children, and in 1933 he moved to the Department of Pediatrics where he established the rst division of Child Psychiatry in an academic setting. Earlier, there were specialists in childrens emotional diculties as part of the mental hygiene

movement, but these were not in academic settings. Kanner also wrote the rst English language textbook in Child Psychiatry, which was rst published in 1935 [1] and went through a number of editions, the last published in 1979. 2. Autistic disturbances of aective contact In 1943, he published a paper in the second volume of a short-lived journal called The Nervous Child called Autistic Disturbances of Aective Contact [2]. The paper described 11 children who had a unique syndrome not heretofore reported (Fig. 1). He proposed two criteria. (1) The outstanding pathognomonic fundamental disorder is the childrens inability to relate themselves in the ordinary way to people and situations from the beginning of life. (2) The childs behavior is governed by an anxiously obsessive desire for the maintenance of sameness that nobody may disrupt (Fig. 2). Such children had been described before as individual cases (e.g., [3]), but no one had brought together a case

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Rigid Socially Awkward Language impaired

Asperger

Rigid

Autism

PDD

Socially Awkward Language impaired

Fig. 1. The autism spectrum as seen in family members.

Many cases now included as autism and spectrum disorders are genetically related to Kanners Severe MR, Dysmorphisms, Known causes, Large gene defects

autism.

Kanners Autism Asperger syndrome Milder spectrum disorders

Other cases now included as autism and PDD are genetically unrelated to Kanners autism.

Fig. 2. Overlap of autism spectrum disorders with Kanners autism.

series and articulated how these children diered from others with mental retardation or language disorders. He called the condition infantile autism because it began early in life and because the childrens lack of interested in other people reminded him of a similar feature of schizophrenia, as described by Eugen Bleuler [4]. The next year, Hans Asperger [5] published a series of four very similar cases in German that he called autistic psychopathy. The only dierence between the two sets of cases is that Asperger did not include any children who had no speech. In recent years, this term has come to be used to designate those children with autism who have normal onset of speech and generally normal intelligence [6] (Table 1).

3. Kanners rst criterion Children with autism have an innate diculty in understanding the nature of human interaction, what use it has, and how to go about it. They also relate strangely to objects. They may be quite interested in certain objects, but they do not play with them in the usual way, and particularly do not engage in social play or imaginative play. He seems self-satised. He has no apparent aection when petted. He does not observe the fact that anyone comes or goes, and never seems glad to see father or mother or any playmate. He seldom comes when called. [2] Until the last year, he mostly ignored other people. When we had guests, he just wouldnt pay any attention.

S.E. Folstein / Clinical Neuroscience Research 6 (2006) 113117 Table 1 Some of the autism spectrum disorders unrelated to Kanners autism Specic genetic conditions Phenylketonuria (PKU) Tuberous sclerosis Neurobromatosis Fragile X Retts syndrome Other PX dysmorphic features 15q1112 maternal duplication Microcephaly Infections Congenital rubella Herpes encephalitis Malaria encephalitis

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When he spun a block, he always start with the same face uppermost. When he threaded buttons, he arranged them in a certain sequence that had no pattern but happened to be the order used by his father when he rst had shown them to Donald [2]. When their routines are disrupted, autistic children become so anxious that they have tantrums, and many of their routines meet criteria for compulsions. Indeed if, like DSM-IV, one does not require obsessions (most autistic children cannot tell you the thoughts driving their compulsive behaviors), 43% meet criteria for OCD [7]. 5. Language in autism Interestingly, Kanner did not include language in his criteria for autism, although he clearly described the unique features of their speech. In DSM-IV, abnormal language development is the second of the three criteria. Children who have normal onset of speech are now called Asperger Syndrome. The list of language features that can qualify for a diagnosis are a mixture of structural language and social use of language. Kanner did not include structural language because it is so variable in autism some children he diagnosed had no speech at all and others achieved entirely normal grammar and syntax, albeit not always at the normal time. The social use of language, pragmatics and prosidy, he included as part of the social abnormalities. Kanner described the childrens early attempts to communicate: Aside from the recital of sentences contained in the ready-made poems or other remembered pieces, it took a long time before they began to put words together . . . When sentences are nally formed, they are for a long time mostly parrot-like repetitions of heard word combinations. They are sometimes echoed immediately, but they are just as often stored and uttered at a later date. Words to him had specic, literal, inexible meaning. The word yes meant that he wanted his father to put him up on his shoulder. His father, trying to teach him to say yes and no, once asked him, Do you want me to put you on my shoulder? If you want me to, say, Yes. Eventually, language becomes somewhat more exible, but even very able persons with autism tend to use the same phrases, sentences, and even paragraphs, repeatedly. This may not always be obvious on rst meeting. 6. Prosody and pragmatics Although prosody and pragmatics are often included as aspects of language, they are quite distinct from vocabulary

He looked curiously at small children and then would go o all alone. He acted as if people werent there at all, even with his grandparents. About a year ago, he began showing more interest in observing them, would even go up to them. But usually people are an interference, Hell push people away from him. If people come too close to him, hell push them away. He doesnt want me to touch him or put my arm around him, but hell come and touch me [2]. It is important to emphasize that autistic children are usually attached to their parents, albeit in a peculiar way. They often (although not always) become anxious when their parents are not present, and may show aection in a stilted way. They depend on their parents entirely to understand and interpret their needs as well as interpret the world around them. Unlike typical children, they do not show their parents things they are interested in or proud of or share information of interest to them. Interest in social interaction gradually increases in those children who develop considerable language, but they nearly always remain socially awkward, with great diculty using their language in a social context. They talk about things that are of no interest to others and have no idea when to allow another person a conversational turn. They have such diculty with putting social events in sequence that they cannot usually be persuaded to report much about their day at school, make up a story, or even understand the plot of stories read to them. 4. Second criterion Kanners second criterion was the anxiously obsessive desire for the maintenance of sameness. A variation of this has become the third DSM-IV criterion, which diers in that it also includes motor repetitions. Classically autistic children cannot tolerate change of any type, either in their physical environment or in the sequence of activities during the day. Changes of routine, of furniture arrangement, of a pattern, of the order in which everyday acts are carried out, can drive him to despair [2].

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grammar, syntax, and morphology (see Tager-Flusberg for denitions) and are present even in very young children who yet have few or even no words. They are universally abnormal in autism, regardless of the level of structural language. Prosody is dened as the nonverbal aspects of communication and includes such things as tone and volume of voice to indicate emotion, gestures used to qualify or elaborate a message or as social niceties, such as gestures related to greeting and parting. It also includes the use of eye contact, which is used to indicate friendliness, attention, or boredom. Pragmatics is closely related, and includes the ability to understand the information needed by ones conversational partner in order to understand your message. It also includes the ability to understand when another person is bored with the topic, and know when to relinquish ones conversational turn. 7. Kanners exclusions Kanner did not diagnose autism in every child who had social impairment or repetitive behaviors. The children Kanner diagnosed needed to look intelligent, to be alert and to show interest in things (although not people). He excluded children who had dysmorphic features or very low IQ, below perhaps 35 or 40. Those children without speech performed well on visualspacial tasks and puzzles. If he had included profoundly retarded children, it would have been much more dicult to make the distinction between autism and mental retardation. Indeed, a major reason (although not the only one) for the increased number of cases now diagnosed is the inclusion of such cases. 8. The spectrum of features found in families of cases meeting Kanners criteria Autism, as dened by Kanner, is a highly familial condition. While the recurrence risk for autism in a family who has an autistic child is probably about 10% or less, it is more common to see Aspergers syndrome and milder social awkwardness, as well as language and reading difculties among siblings. Some years ago, we contacted as many of the rst 100 families diagnosed by Kanner and asked their mothers about their other children. We took similar histories from the mothers of adults with autism who met DSMIII-R criteria. The dierences were striking. Fully 36% of siblings of Kanners cases had autism, severe social dysfunction (now called Asperger syndrome), or language/reading disorders. The numbers exceeded 50% when medication-treated mood disorders were included. In contrast, only 6.6% of the other adults had similarly aected siblings [8]. A similar spectrum of conditions is seen in monozygotic twins. If only strictly diagnosed autism is included, about 60%65% are both aected but if milder forms are included the proportion increases to 90% [9].

It is important to note that mental retardation is quite uncommon among the siblings of strictly diagnosed autism cases. In fact, the siblings tend to have unusually high intelligence [10,11]. 9. Spectrum disorders etiologically unrelated to Kanners autism The autism diagnosis is now applied to a much broader range of cases including those who have profound mental handicap, dysmorphic features, and specic etiologies. Some of these are conditions with both particular physical features or a known etiology (such as Fragile X syndrome, Retts syndrome, tuberous sclerosis, or untreated phenylketonuria); others are children with no named syndrome but have detectable cytogenetic abnormalities, such as maternally transmitted duplication of chromosome 15q1112; still others are caused by early severe infections, such as congenital rubella, herpes encephalitis, or cerebral malaria [12,13]. The etiological dierences related to the presence of dysmorphic features is well illustrated by a recent paper by Miles et al. comparing cases with and without dysmorphic features. Those without dysmorphic features (except for macrocephaly) had a higher male:female ratio, more aected family members, higher IQ and better outcomes [14]. References
[1] Kanner L. Child Psychiatry. Springeld IL CC Thomas Publishing Co.; 1935. [2] Kanner L. Autistic disturbances of aective contact. The Nervous Child 1943;2(3):21750. [3] Ssucharewa GE, Wol S. The rst account of the syndrome Asperger described? Translation of a paper entitled Die schizoiden Psychopathien im Kindesalter by Dr. G.E. Ssucharewa; scientic assistant, which appeared in 1926 in the Monatsschrift fur Psychiatrie und Neurologie 60:23561. Eur Child Adolesc Psychiatry 1996;5(3):11932. [4] Bleuler E. Textbook of Psychiatry (translated by AA Brill). 4th ed. New York: MacMillan; 1924. [5] Asperger H. Die Autistischen Psychopathen im Kindesalter. Archiv fur Psychiatrie und Nervenkrankheiten 1944;117:76136. [6] Wing L. Aspergers syndrome: a clinical account. Psychol Med 1981;11(1):11529. [7] Tadevosyan-Leyfer T, Folstein S., Bacalman S., Davis N Dinh E, Morgan J, Tager-Flusberg H, Lainhart JE. Comorbid psychiatric disorders in children with autism: interview development and rates of disorders. J Autism Dev Disord, 2006, in press. [8] Piven J, Gayle J, Chase G, Fink B, Landa R, Wzorek MM, Folstein SE. A family history study of neuropsychiatric disorders in the adult siblings of autistic individuals. J Am Acad Child Adolesc Psychiatry 1990;29:17783. [9] Bailey A, Le Couteur A, Gottesman I, Bolton P, Simono E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25(1):6377. [10] Freeman BJ, Ritvo ER, Mason-Brothers A, Pingree C, Yokota A, Jenson WR, McMahon WM, Petersen PB, Mo A, Schroth P. Psychometric assessment of rst-degree relatives of 62 autistic probands in Utah. Am J Psychiatry 1989;146(3):3614. [11] Folstein SE, Santangelo SL, Gilman SE, Piven J, Landa R, Lainhart J, Hein J, Wzorek M. Predictors of cognitive test patterns in autism families. J Child Psychol Psychiatry 1999;40(7):111728.

S.E. Folstein / Clinical Neuroscience Research 6 (2006) 113117 [12] Folstein S, Rosen-Sheidley B. Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2001;2(12):94355. [13] Mankoski R, et al. Etiologies of Autism in a Case-series from Tanzania, J Autism Dev Disord, 2006, in press.

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[14] Miles JH, Takahashi TN, Bagby S, Sahota PK, Vaslow DF, Wang CH, Hillman RE, Farmer JE. Essential versus complex autism: denition of fundamental prognostic subtypes. Am J Med Genet A 2005;135(2):17180.