Is it autism?

Is it autism? By John D. Rau, MD Autism and related pervasive developmental disorders are a challenge to diagnose. This review covers diagnostic criteria, conditions to consider in the differential, the evaluation, and treatment options. Conditions discussed in this article Autistic disorder Kanner's autism Asperger's disorder Rett's disorder Childhood disintegrative disorder Pervasive developmental disordernot otherwise specified Fragile X syndrome Landau-Kleffner syndrome "Autism" has been in the lexicon of physicians for almost 100 years, but its meaning has changed considerably during that time. The word appears to have been used first by Swiss psychiatrist Eugen Bleuler in 1911 and was derived from the Greek autos (self) and ismos (condition). Bleuler applied the concept of "turning inward" on oneself to adult patients with schizophrenia, then called dementia praecox. Before 1943, autism was equated with an involutional symptom characteristic of adult schizophrenia, and childhood autism was conceptualized as a form of schizophrenia or thought disorder. In 1943, American child psychiatrist Leo Kanner defined "infantile autism" and described its clinical features in a way that separated this entity from schizophrenia.1 Today, experts believe that autism is likely a heterogeneous group of behavioral disorders, which are diagnosed on the basis of subjective criteria. Pediatricians must, therefore, be familiar with the specific criteria for diagnosing autism and with the characteristics of conditions to consider in the differential. Kanner's autism In Kanner's 1943 article, "Autistic Disturbances of Affective Contact," he presented the cases of 11 children observed since 1938 who exhibited what Kanner believed to be a new syndrome ("infantile autism") characterized by "extreme autism, obsessiveness, stereotypy and echolalia."1 According to Kanner, a significant difference between schizophrenia and this newly described condition was that children with schizophrenia had a period of "average development" before symptoms appeared, whereas children with infantile autism showed their extreme aloneness very early in life. He suggested that autism was a syndrome based on impairment of development rather than an acquired psychopathology.1 The classic features of what became known as Kanner's autism include gross and sustained impairment in social interaction and communication. Patients also demonstrate restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The severity of autistic features varies greatly along what is termed the pervasive continuum. Associated disorders include mental retardation (75% to 80%), idiosyncratic and echolalic speech, seizures, attention deficit hyperactivity disorder (ADHD), eating disorder (pica or restricted variety), self-injurious behavior, abnormal moods, and behavioral diagnoses such as depression. Kanner's autism includes the following characteristics: extreme autistic aloneness anxiously obsessive desire for the preservation of sameness Excellent rote memory Delayed echolalia Oversensitivity to stimuli Limitations in the variety of spontaneous activity Good cognitive potential Highly intelligent family Inclusion of "highly intelligent family" as a characteristic was probably a reflection of the upper middle class patients that Kanner treated in his practice. The "good cognitive potential" was based on his observation that these children had excellent memories and fine motor skills.2 (Many parents and practitioners believe there is great intellectual potential among children with autismif only it could be released. Some children do indeed have amazing "splinter skills"unusual or unexpected, narrowly focused skills, such as in memory or calculation, that exceed performance in most other areas.) Asperger's autism Unaware of Kanner's writings, in 1944 Austrian psychiatrist Hans Asperger published a paper, "Die 'Autistichen Psychopathen' des Kindesalter" (The Autistic Psychopathy of Childhood), that described four cases of what would now be termed high-functioning autism.3 Asperger's paper remained almost unknown in the United States and other English-speaking countries until referenced in a paper by Lorna Wing in 1981 and translated into English in 1991.4 Some of Asperger's observations were similar to Kanner's case studies. Like Kanner, he used "autistic" to mean an impairment in social interaction. He further noted: A much greater frequency of autistic psychopathy in boys The absence of autism in infancy and often through the age of 3 years "Normal" speech development, although possibly abnormal pronoun usage and language content A possible delay in the developmental milestone of walking, with gross motor clumsiness and poor coordination Impaired nonverbal communication Significant impairment in reciprocal social interactions as the primary characteristic Enjoyment of repetitive activities such as spinning an object Resistance to change or difficulty in making transitions Excellent rote memory Intense interest in one or two areas to the exclusion of everything else Many school problems owing to eccentric behaviors and the wish to follow personal interests rather than the teacher's direction Table 1 details the similarities and differences in Kanner's autism ("classic" autism) and Asperger's autism, the latter of which has come to be called Asperger's disorder or Asperger syndrome. TABLE 1 Comparing Kanners and Aspergers autism A criterion-based diagnosis Table 2 lists red flags that suggest autism. In the presence of such flags, the following questions confront the practitioner5: 1. How is autism diagnosed? (What are the diagnostic criteria? How reproducible is the diagnosis? What test data support or refute the diagnosis?) 2. What conditions do I need to consider in the differential diagnosis? 3. If this child has autism, what are the management options? 4. What is the prognosis for the child and family? TABLE 2 Red flags for autism in a child Unusual speech Does not relate socially Pervasive (repetitive, randomly occurring, nonfunctional) behaviors such as hand flapping or rocking Poor eye contact Fascination with spinning self or objects, water, mirrors, ceiling fans, lining up toys (among other fascinations) Absence of pointing to show or request something Lack of interest in baby games, such as peek-a-boo Parents complain that child is unresponsive to them History of being "a very good baby," "never cried" An example of a criterion-based behavioral construct, autism (also called autistic disorder), together with Rett's disorder (Rett syndrome), childhood disintegrative disorder (Heller syndrome), Asperger's disorder (Asperger syndrome) and pervasive developmental disorder-not otherwise specified (PDD-NOS; atypical autism), comprise a group of disorders collectively termed pervasive developmental disorders. This nomenclature is confusing, especially when trying to explain a diagnosis of autistic disorder versus PDD-NOS to a family. The pervasive developmental disorders range in severity, are usually diagnosed in infancy, childhood, or adolescence, and are lifelong conditions with social consequences. The term autism spectrum disorder has different meanings depending on the context in which it is used. It can be used to denote all five disorders within the category of pervasive developmental disorders; to indicate autistic disorder, PDD-NOS, and Asperger's disorder; or to mean just autistic disorder and PDD-NOS. Several useful manuals list the diagnostic criteria for the pervasive developmental disorders, including: Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, Text Revision, (DSM-IV-TR) American Psychiatric Association, 2000 The Classification of Child and Adolescent Mental Diagnoses in Primary Care, Diagnostic and Statistical Manual for Primary Care (DSM-PC), Child and Adolescent Version, American Academy of Pediatrics, 1996 Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood. Diagnostic Classification: 03, Zero to Three/National Center for Clinical Infant Programs, 1994 Because much of the research into the diagnosis and treatment of pervasive developmental disorders uses the DSM fourth edition text revision, the diagnostic criteria presented in this article are from that manual. The DSM-IV-TR criteria are also closely linked to billing codes that can help maximize reimbursement for primary care physicians. The "Diagnostic criteria for autistic disorder" box in the print edition (Reprinted with permission from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Copyright 2000, American Psychiatric Association) lists the diagnostic criteria for autistic disorder. These focus on the three main areas originally suggested by Kanner: impaired social interaction, impaired communication, and a restricted range of activities and interests. Autistic disorder may be diagnosed when a child meets six of the 12 criteria from part A, at least two from point 1 and at least one each from points 2 and 3. In addition, onset of symptoms should occur before age 3 years and not be better accounted for by Rett's disorder or childhood disintegrative disorder (the criteria for these two conditions are presented later). No specific laboratory tests, psychoeducational instruments (developmental, IQ, and achievement testing), or computer tests aid in the diagnosis of autism. Several autism rating scales are designed to support a diagnosis of autism, but they are neither necessary nor sufficient to make the diagnosis. Autism is a relatively subjective diagnosis made by applying behavioral diagnostic criteria of DSM-IV-TR to information derived from many sources, including preschool or school, home and family, the child's physician, and the medical, social, and family history. Diagnosing classic autismthat is, a child who has many or all of the attributes originally described by Kanneris often straightforward. Milder forms of autism that still meet DSM-IV-TR diagnostic criteria for either autistic disorder, PDD-NOS, or Asperger's disorder are more difficult to differentiate from other developmental disorders and, at times, lead to diagnostic differences among child development professionals. When the diagnosis in a child is disputed among professionals, it is important to perform multiple evaluations over time until his (or her) difficulties are illuminated. Etiology of autism: More questions than answers Prevalence data at one time suggested that autism occurs at a rate of two to five cases for every 10,000 children under the age of 15 years. More recent data, however, indicate a significant increase in the occurrence of autistic disorder. A prevalence rate of one to two for every 1,000 children has now been established from recent population-based studies.69 Whether the increase in the diagnosis of autism is due to increasing awareness of the condition, a relaxation of diagnostic criteria, a greater inclination within the medical and psychologist communities to make this diagnosis, or some other cause (e.g., environmental toxins, injury, infection) is unknown. Autism is three to five times more common in males than in females. No specific anatomic or pathophysiologic etiology for infantile autism has gained universal support. Many biologic causes have been proposed, including intrauterine rubella infection, tuberous sclerosis, traumatic brain injury, hydrocephalus, phenylketonuria, infantile spasms, and herpes simplex encephalitis. However, most children with autism do not exhibit any detectable biologic disorder. Evidence is growing to strongly support genetic inheritance as an important but not sole contributor to autism, and the search for specific autism genes is under way. These data derive from family and twin studies that indicate a 5% to 8% recurrence risk for a family with one affected child. A high concordance rate (if one twin is affected then the other twin will be affected) for monozygotic (identical) twins and a significantly lower concordance rate for dizygotic (fraternal) twins has been reported.10,11 Childhood immunizations have been proposed as a cause of autism by several people through the national news media and on the World Wide Web. Some members of Congress have announced that childhood immunizations have harmed persons in their own families and, in one case, reported that a grandchild's autism was caused by a routine immunization. Usually the measles-mumps-rubella (MMR) immunization is the vaccine suspected to cause autism, although others have also been implicated. There is no evidence to support a causal link between autism and MMR or other vaccines used in immunizations.12 In fact, two recent retrospective studies using large population registriesmore than 500,000 children eachfrom Denmark and Finland demonstrated no association between MMR immunization and autism.13,14 Nevertheless, the Centers for Disease Control and Prevention, the Food and Drug Administration, the National Institutes of Health, and other federal agencies continue to monitor and research the safety of vaccines used in the US. Disorders to consider in the differential The differential diagnosis of autism includes other pervasive developmental disorders: Rett's disorder, childhood disintegrative disorder, Asperger's disorder, and PDD-NOS. The diagnostic criteria for these disorders are shown in the boxes in the print edition (Reprinted with permission from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Copyright 2000, American Psychiatric Association). In the past, Rett's disorder and fragile X syndrome (discussed in detail later) were often diagnosed as autism. Rett's disorder is differentiated from autism by a period of normal development and normal head circumference through the age of 5 months, followed by deceleration of head growth and loss of purposeful hand skills, with the appearance of hand wringing, other hand stereopathies, gait abnormalities, and social withdrawal. Rett's disorder has been reported only in females, affecting about 1 in 10,000 females. Recent reports suggest that the gene MECP2 on the X chromosome is the genetic abnormality responsible for this syndrome. Similarly, childhood disintegrative disorder is characterized by an initial period of normal development, which lasts for about two years. Significant loss of skills occurs in at least two of the following categories: language, social or adaptive behavior, bowel or bladder control, play, and motor skills. Severe mental retardation is common, along with other signs of central nervous system dysfunction such as seizures and electroencephalogram (EEG) abnormalities. Childhood disintegrative disorder is much less common than autism.15 PDD-NOS should be diagnosed when there is a "severe and pervasive impairment" in social skills or verbal or nonverbal communication, or when stereotyped behavior, interests, and activities exist but do not meet the criteria for another pervasive developmental disorder, especially autism. (The child is autistic-like but does not meet the criteria for autistic disorder.) There is often considerable disagreement among professionals, however, as to whether a child has PDD-NOS or autism. Children who have cognitive impairments in the moderate or severe-to-profound range often have pervasive behaviors such as hand flapping, or squealing with jumping up and down. This does not necessarily mean the child has autism. Asperger's disorder has diagnostic criteria similar to those of autism except that, in Asperger's disorder, there is no clinically significant delay in language, cognition, or adaptive behavior other than in social interaction. That Asperger's disorder has become a more frequent diagnosis may be because patients, families, and professionals equate it with "high-functioning" autism. In our experience, it is less common to see children who meet the criteria for Asperger's disorder. Conditions not severe enough to meet the criteria for autistic disorder can usually be diagnosed as PDD-NOS rather than as Asperger's. Conditions other than the pervasive developmental disorders should also be considered in the differential diagnosis for autism. The list includes fragile X syndrome, the diagnostic criteria of which are listed in the "Diagnostic criteria for fragile X syndrome" box. The second most common genetic cause of mental retardation after Down syndrome, fragile X syndrome results from an expanded, methylated gene on the X chromosome at the q27.3 position (q indicates the long arm of the chromosome). The preferred diagnostic test is a DNA fragile X analysis. Studies on populations screened for the syndrome have indicated wide variation in the prevalence of patients who meet the criteria for autism among those testing positive for fragile X syndrome. These findings range from 5% to 60%, with several studies showing that more than 20% of persons with autism have fragile X syndrome. Conversely, studies searching for positive fragile X syndrome tests in populations of patients with autism range from 0% to 16%, with a mean of 4%. There is an overlap between autism and fragile X syndrome, but the effect does not appear to be large.16 Recent investigations of children with autism spectrum disorder suggest a possible connection to another condition: Landau-Kleffner syndrome. This syndrome is an acquired aphasia with seizures and abnormal EEG discharges in childhood after previously normal language development. Mean age of onset of the syndrome is about 4 years, with a range of onset from 1 to 14 years. An affected child may gradually lose the ability to understand language. Parents often think that the child has become deaf.17 Until recently, Landau-Kleffner syndrome was thought to be a convulsive disorder that could be successfully treated with anticonvulsants; such therapy often resulted in at least partial improvement in language abilities. An innovative research technique called magnetoencephalography has been used to investigate possible overlap between Landau-Kleffner syndrome and autism spectrum disorder. Results of this study indicate that previous undetected epileptiform abnormalities are found in a significant percentage of children with autism and PDD-NOS.18 Further research will help to define the relationship between Landau-Kleffner syndrome and autism spectrum disorder.15 Among the other conditions that may need to be differentiated from autism are schizophrenia, communication disorders, selective mutism, sensory impairments, Tourette syndrome, psychosocial deprivation, and mental handicap (mental retardation). Medical assessment should be comprehensive The recommended medical evaluation includes medical and family history with a thorough physical examination. The physical examination can be very useful in identifying unusual language (or lack of language), quality of social interaction, problems with transition from playroom to exam room, lack of eye contact, hand flapping, and other pervasive behaviors. Although no specific laboratory tests for autism exist, some tests are recommended. These include screening with a urine specimen for inborn organic acidemias and other metabolic disorders, and a DNA fragile X analysis. An audiologic evaluation should be performed. Staring off into space is a common behavior for children with autism, and frequent staring episodesreported by many parents and teachers of autistic childrenmust be differentiated from absence seizures, which may coexist with autism. Absence seizures are brief with very rapid recovery and no memory of the time lapse. If the child has staring spells and the medical history is not precise enough to determine whether they are behavioral or a convulsive event, obtain an EEG evaluation. Diagnostic imaging of the central nervous system should be considered when indicated by the history and physical examination, such as in cases of microcephaly, macrocephaly (other than familial), a history of trauma, or focal neurologic signs. Evaluations from other disciplines that may contribute to the assessment include clinical or education psychology, speech or language pathology, social work, nursing, nutrition, and physical and occupational therapy. An experienced early childhood interdisciplinary team often offers an ideal way to evaluate a child with possible autism, especially in cases in which the diagnosis is difficult or in dispute. Evaluation teams exist in most schools. Local schools can provide informed referrals for more complete and complex interdisciplinary evaluations often located in children's medical centers. Pharmacotherapeutic options Treatment for autism, as well as for many other developmental disorders, must begin early, continue for many years, and involve many disciplines. Priority interventions for autism include behavior management, development of a communication system, social skills training, life skills training, occupational and physical therapies, and special educational programming; again, all beginning at an early age. Several excellent studies have evaluated the efficacy of specific interventions and therapies in children with autism and have shown them to be effective in improving the quality of life for these children and their families.19,20 These therapies do not "cure" autism but can maximize educational and behavioral outcomes. Prognosis is variable and individualized. General prognoses cannot be made; if, however, a child has no system of communication by age 5 or 6, significant communication and educational problems are likely. No specific medication successfully treats the underlying constellation of neurologic symptoms. Pharmacotherapy targeted to behaviors such as hyperactivity, aggression, self-injury, convulsive events, ritualistic behaviors, sleep disorders, and depression may be used in selected patients for desirable behavioral and educational goals. Many psychotropic medications are prescribed for autistic children, among them: The alpha2-adrenergic agonists clonidine and guanfacine, for hyperactivity and sleep problems Tricyclic antidepressant agents, such as imipramine, nortriptyline, and clomipramine, for depression and obsessive-compulsive behavior (use with caution in children) Selective serotonin reuptake inhibitors, such as fluvoxamine, fluoxetine, paroxetine, and sertraline, for depression and obsessive-compulsive behavior Antipsychotic medications thioridazine, risperidone, and olanzapine for rage and aggression Antianxiety agents such as the benzodiazepines lorazepam and clonazepam for anxiety and panic attacks Other medications that have been used include buspirone, an antianxiety medication; buproprion, an antidepressant; and two anticonvulsant medicationscarbamazepine and valproic acidfor seizures and mood swings, rage, and aggression. The safety profile of many of these medications is not well known in children, and their off-label use carries a warning recommending caution in patients under 18 years of age. The cautions exist for each medication prescribed by itself; when two or more psychotropic medications are used together, the interaction profile is often unknown. One study, under way at our hospital, investigates the effects of risperidone on children with autism. More studies of this type are needed to delineate the role of psychotropic medication in children who already have developmental problems. Secretin does not have a role in the treatment of autism, although some parents mistakenly believe otherwise. In 1999, the media trumpeted the report that human secretin administered to an autistic boy undergoing a gastrointestinal procedure seemed to resolve his speech and pervasive behavioral problems. News programs interviewed several mothers who anecdotally reported that treatment of their children with secretin resulted in astonishing improvement in their autism. Overnight, the supply of human secretin became scarce nationwide (our child development center received hundreds of calls for secretin). Many parents searched for secretin using Internet chat rooms or listservs. The fact is, several studies have documented that secretin is ineffective in treating the behavior and language problems of autistic children, and it should not be recommended for patients who have autism.21 A multidisciplinary approach to care Resources exist in small and large, urban and rural communities that can assist practicing physicians in caring for and providing specialized services for children with autism and other developmental problems: The local educational system. For access to special education services, contact the state's department of special education. States have booklets and brochures that specify eligibility requirements and means of entering services. Local chapters of parent and support groups, such as the Autism Society of America Agencies and organizations that offer respite care Facilities that provide special-needs summer camping experiences Private therapists, especially in speech or language, occupational therapy, and physical therapy to supplement such services provided by the local school system Private behavioral specialists Clinical and school psychologists employed by the school and in private practice Special developmental preschools The state's early intervention program for children from birth to 3 years It is important to involve families as partners in assessment and intervention while providing referrals, support, and advocacy as required. Highly successful professionals in early childhood intervention, education, and health care accept families as co-therapists and teachers of their own children. As the child's physician, you are uniquely qualified to provide the family with adequate supports to ensure optimal outcomes for their children. You are also in a position to guide families to sources of information about their children's developmental difficulties. The "A sampling of Web sites with content about autism" box lists some Web sites specifically about autism. Many additional links are available from these sitesnot all of which are recommended. Because many families find information through the Internet (at our child development center, as many as 60% of families have obtained information about their child's developmental problem from the Web), it is important for physicians to be knowledgeable about all these sites, not just the recommended ones. Caution parents that, although some information on the Web is accurate, helpful, and up to date, other information is not. In addition, some Web sites attempt to sell products or services that have not been rigorously tested for safety and efficacy. Alternative therapies It is not surprising that pervasive developmental disorders invite many nontraditional therapies, given that the causes of these disorders are unknown, the diagnosis is made by applying a set of subjective criteria, the treatment is not curative, and the prognosis carries lifelong consequences for patient and family. Proponents of some nontraditional therapies are overly hopeful; some claims are outright fraudulent. Many alternative therapies (which could more aptly be termed unproven therapies) are marketed to families without any proof of validity or efficacy and with exaggerated claims. Such therapeutic modalities include facilitated communication, immune therapy, dimethylglycine with pyridoxine and magnesium, megavitamin therapy, auditory integration therapy, treatment for fungal infections (yeast), and the use of tinted glasses. I do not believe that any of these treatments warrants the time and money often required for families to secure these false "cures." [Editors' note: For more information on alternative therapies, see "Autistic spectrum disorders: When traditional medicine is not enough" in the October 2000 issue.] Directions for the future in autism studies Autistic disorder is a criterion-based diagnosis that depends on subjective determinations of the presence of specific pervasive behaviors. So far, two diagnostic categories that were considered autism in the past have been separated from autistic disorder: Rett's disorder and fragile X syndrome (although the latter may coexist with autism). Almost certainly, others will be similarly differentiated. To increase our understanding of autism and other pervasive development disorders, it is critical to: Discover the cause (or causes) Develop a confirmatory laboratory test Find the gene product that is abnormal Explore the interaction of environment with genetics Create therapies that address the underlying molecular and developmental problems The knowledge base of pervasive developmental disorders will be expanded through scientific research. It is important, I believe, to utilize scarce resources to increase scientific knowledgenot to evaluate the latest anecdotal cause of, or therapy for, autism. This is a very promising time for research that links findings from molecular genetics to behavioral disorders in children. REFERENCES 1. Kanner L: Autistic disturbances of affective contact. The Nervous Child 1943;2:217 2. Kanner L: Early infantile autism. J Pediatr 1944; 25:211 3. Asperger H: Die 'autistischen psychopathen' im kindesalter. Archiv fur Psychiatrie und Nervenkrankheiten 1944;117:76 4. Wing L: Asperger's syndrome: A clinical account. Psychol Med 1981;11:115 5. Committee on Children With Disabilities: American Academy of Pediatrics: The pediatrician's role in the diagnosis and management of autistic spectrum disorder in children. Pediatrics 2001;107:1221 6. Rapin I: Autism. New Engl J Med 1997;337:97 7. Bauer S: Autism and the pervasive developmental disorders, Part 1. Pediatr Rev 1995;16:130 8. Bauer S: Autism and the pervasive developmental disorders; Part 2 Pediatr Rev 1995;16:168 9. Bertrand J, Mars A, Boyle C, et al: Prevalence of autism in a United States population: The Brick Township, New Jersey, investigation. Pediatrics 2001; 108:1155 10. Szatmari P: Heterogeneity and the genetics of autism. Journal of Psychiatry and Neuroscience 1999; 24(2):159 11. Bailey A, Le Couteur A, Gottesman I, et al: Autism as a strongly genetic disorder: Evidence from a British twin study. Psychol Med 1995;25(1):63 12. Fombonne E, Chakrabarti S: No evidence for a new variant of measles-mumps-rubella-induced autism. Pediatrics 2001:108:e58 13. Madsen KM, Hviid A, Vestergaard M, et al: A population-based study of measles, mumps, and rubella vaccination and autism. New Engl J Med 2002;347:19 14. Mäkelä A, Nuorti P, Peltola H: Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 2002;110:957 15. Fombonne E: Prevalence of childhood disintegrative disorder. Autism 2002;6:149 16. Feinstein C, Reiss A: Autism: The point of view from fragile X studies. Journal of Autism and Developmental Disorders 1998;28:393 17. Landau WM, Kleffner FR: Syndrome of acquired aphasia with convulsive disorder in children. Neurology 1957;7:523 18. Lewine JD, Andrews R, Chey M, et al: Magnetoencephalographic patterns of epileptiform activity in children with regression autism spectrum disorders. Pediatrics 1999;104:405 19. Blackman JA: Early intervention: A global perspective. Infants and Young Children 2002;15(2):11 20. Rogers SJ: Intervention for young children with autism: From research to practice. Infants and Young Children 1999;12(2):1 21. Lightdale JR, Hayer C, Duer A, et al: Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: A single-blinded, open-label pilot study. Pediatrics 2001;108:e90 DR. RAU is director of the Riley Child Development Center, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Ind. Dr. Rau has nothing to disclose in regard to affiliation with, or financial interests in, any organization that may have an interest in any part of this article. A mnemonic for Kanner's autism Aloneness Understanding, lack of Touch, oversensitivity to Irrelevant and metaphorical language Sameness, desire for Memory, rote Diagnostic criteria for childhood disintegrative disorder (Heller syndrome, dementia infantilis, or disintegrative psychosis) International Classification of Diseases code 299.10 A. Apparently normal development for at least the first 2 years after birth as manifested by the presence of age-appropriate verbal and nonverbal communication, social relationships, play, and adaptive behavior B. Clinically significant loss of previously acquired skills (before age10 years) in at least two of the following areas: 1. Expressive or receptive language 2. Social skills or adaptive behavior 3. Bowel or bladder control 4. Play 5. Motor skills C. Abnormalities of functioning in at least two of the following areas: 1. Qualitative impairment in social interaction (e.g., impairment in nonverbal behaviors, failure to develop peer relationships, lack of social or emotional reciprocity) 2. Qualitative impairments in communication (e.g., delay or lack of spoken language, inability to initiate or sustain a conversation, stereotyped and repetitive use of language, lack of varied make-believe play) 3. Restricted, repetitive, and stereotyped patterns of behavior, interests, and activities, including motor stereotypies and mannerisms D. The disturbance is not better accounted for by another specific pervasive developmental disorder or by schizophrenia. Reprinted with permission from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,Text Revision. Copyright 2000, American Psychiatric Association Diagnosing pervasive developmental disorder, not otherwise specified (including atypical autism) International Classification of Diseases code 299.80 This category should be used when there is a severe and pervasive impairment in the development of reciprocal social interaction or verbal and nonverbal communication skills, or when stereotyped behavior, interests, and activities are present, but the criteria are not met for a specific pervasive developmental disorder, schizophrenia, schizotypal personality disorder, or avoidant personality disorder. For example, this category includes "atypical autism"presentations that do not meetthe criteria for autistic disorder because of late age at onset, atypical symptomatology, or subthreshold symptomatology, or all of these. Reprinted with permission from Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,Text Revision. Copyright 2000, American Psychiatric Association Diagnostic criteria for fragile X syndrome DNA fragile X analysis: fragment size (2.3 male; 2.8 and 5.2, female) CGG repeat number (5-55) Fragile X status: normal, permutation, full mutation, or mosaic Chromosome analysis of lymphocytes grown in folate deficient media (positive from fragile site at Xq27.3 in 1% to 50% of cells) Features of syndrome Large or prominent ears Long face Hyperextensibility of fingers and wrists Macroorchidism (postpubertal) Significant hyperactivity and short attention span Language delays Hypotonia Hand flapping and hand biting Poor eye contact or eye avoidance A sampling of Web sites with content about autism http://www.cdc.gov/nip/vacsafe/concerns/autism/autism-facts.htm Facts about autism from the Centers for Disease Control and Prevention http://www.autism-society.org Autism Society of America http://www.nlm.nih.gov/medlineplus/autism.html MEDLINE plus autism information http://www.naar.org National Alliance for Autism Research http://health.nih.gov National Institutes of Health health information page (click on "A" or search for "autism") http://www.AspenNJ.org Asperger Syndrome Education Network http://www.patientcenters.com/autism/ Patient-Centered Guides, Autism Center http://www.autism.org Center for the Study of Autism http://www.autism-pdd.net/autism.htm The Autism-PDD Resources Network http://www.udel.edu/bkirby/asperger/frame2.html Online Asperger Syndrome Information & Support http://www.aspergers.com Asperger's Disorder homepage