Clinical Manifestations

Autism spectrum disorders (ASD) develop prior to age three years. Infants typically do not care to be held or cuddled and do not reach out to be picked up. Often they are "colicky" and hard to console, typically quieting more readily when left alone. They may avoid and fail to initiate eye contact or stare into space. Sleep disturbances and sensory issues may be noted in the first year. Despite early signs, children with ASD often do not come to medical attention until after the second year when language delays are obvious.

For most children, the onset of ASD symptoms is gradual; however, approximately 30% have a "regressive" onset. These children begin to speak and then, either gradually or precipitously, lose language and become distant. Within a matter of days, the child may refuse to make eye contact and stop responding to his/her name. Deafness is often suspected, although hearing tests are normal. Repetitive movements may develop immediately or not until the child is age three or four years. Though it has been debated whether these children are well and then become damaged by some exogenous exposure, the best evidence, including retrospective analysis of first birthday videotapes and neuropathologic studies, suggests their regressive course is genetically determined [Lord et al 2004, Volkmar et al 2005, Werner & Dawson 2005, Stefanatos 2008].

Approximately 25% of children who fit the diagnostic criteria for ASD at age two or three years subsequently begin to talk and communicate and by age six or seven years blend to varying degrees into the regular school population. Even for this group, social impairments generally continue. For the remaining 75%, most have some improvement with age but continue to require parent, school, and societal support. Excellent reviews of outcomes are provided by Howlin et al [2000], Howlin et al [2004], Seltzer et al [2004], and Farley et al [2009]. Some studies indicate that fewer than 5% of children with autism completely recover [Nordin & Gillberg 1998]; however, loosening of diagnostic criteria to include less impaired children appears to be increasing that number. A 20-year follow-up of adults between ages 22 and 46 years diagnosed with autism and average or near-average cognitive abilities in the 1980s found that half the individuals functioned quite well and half were employed in full-time or part-time paying jobs; however, only 12% lived independently and 56% lived with their parents [Farley et al 2009].

Autism spectrum disorders are defined completely on the basis of three areas of behavioral impairment:

• Impairments in social interaction. Impairment in social interaction distinguishes individuals with autism from those around them. Children with classic autism are unable to "read" other people, ignoring them and often strenuously avoiding eye contact. Typically, they do not comfort others or seek comfort and do not share interests with others, such as bringing toys or pictures to their parents. Rather, they use their parents as objects, and may climb on them to get to a desired object, pull the parent by the hand, or place the parent's hand on the object, as if the child were using a tool. In clinic, the child who is content to turn pages of a magazine or spin the wheels of a car may become agitated when a simple examination is attempted. At home, the child with autism usually prefers to be by himself, engaging in his own, often repetitive, activities. The lack of functional or spontaneous make-believe play is characteristic. Toys are lined up, sorted, twirled, or hurled, but are not used for imaginative games or imitation of day-to-day activities, such as feeding the baby or washing the dishes. When play emerges later, it is stylized and not spontaneous. Children with autism fail to develop friendships with peers and siblings. In school, they often stand and watch other children from a distance. Some children respond to social overtures but take little social initiative, while others seek interaction but have little sense of how to proceed toward normal friendships.
• Impairments in communication. Children with autism fail to develop reciprocal communication either by speech, gestures, or facial expressions. Characteristically, young children fail to use eye gaze or pointing to communicate and direct their parent’s attention. Early pragmatic skills are limited and are characterized by typical rates of requesting but substantially reduced rates of social interaction and establishing joint attention. Deficits in pragmatic skills are present throughout life and affect both language and social interaction. The young child appears unable to grasp the concept that speech can be used to name objects, to request a toy, or to engage others. In contrast to the child with nonspecific intellectual disability or a primary developmental language disorder who usually has better receptive than expressive language, the child with autism has impaired receptive language. When children with autism learn to talk, they display stereotypic speech that may involve echolalia, pronoun reversal, and unusual inflections and intonations. Unlike typically developing children who begin talking using one-word utterances, children with autism may begin talking in "chunks" composed of commercials, movies, or others' speech. These chunks often convey idiosyncratic meanings and the child with autism has no understanding of the conventional meaning of the individual words. Pragmatic difficulties including difficulties sustaining a conversation, turn taking, and allowing the conversational partners to introduce their topics, usually continue despite improvement in expressive speech. [Lord et al 2004].
• Repetitive and stereotypic behaviors. Infants may stare or rock. Toddlers may have motor "stereotypies" such as movements of fingers, twirling strings, flicking pages of books, or licking. Repetitive whole body movements may include spinning and running back and forth. The repetitive behaviors often have a visual component such as holding the fingers to the side of the face and watching them with a sideways glance. Sometimes the movements become more complex with an individualized sequence of patting, rubbing, or twirling. These stereotypies may last for hours. Though the cause of the repetitive movements is unclear, they seem to have a calming effect and may (especially in the older child) surface in times of stress. This repetitiveness is reflected in a rigid need for sameness in daily routines. Children with autism can develop elaborate rituals in which the order of events, the exact words, and the arrangement of objects must be followed. Failure of parents/caretakers to follow the proscribed order of events results in inconsolable outbursts.

Other symptoms occurring in a substantial number of individuals with autism spectrum disorders:

• Hyper- and hyposensitivities to sound and touch. Loud or high-pitched noises such as the vacuum cleaner cause great discomfort, causing the child to hold his hands over his ears. The feel of certain clothes or of being touched may be unbearable; conversely, truly painful stimuli like a burn or laceration are ignored.
• Odd behaviors around foods and their presentation, such as accepting a limited number of foods or only eating french fries that come from McDonalds^®.
• Abnormal sleep patterns (60%), such as never sleeping through the night, trouble going to sleep, or getting up for the day at 2:00 am.
• Tantrums and/or self-injurious and aggressive behaviors brought on by a change in routine, an offending touch, being asked to do something they do not want to do, or for no apparent reason.
• Impaired motor development with toe walking early in life, hypotonia, general clumsiness, and inability to ride a two-wheel bicycle.
• Total disregard for danger, resulting in high risk of early death, commonly from drowning.

Evidence suggests that as many as 15% of adolescents or young adults with autism develop a catatonia syndrome associated with marked deterioration in movement with slowness and freezing in mid-movement, vocalizations, and regression of self-care skills.

Obesity is a common complication of unknow cause. Medication side-effects, inactive life style and difficulty withholding food from children with aggression may be implicated.

Delineation of ASD subgroups. In an attempt to sort out the clinical and etiologic heterogeneity within autism, researchers are increasingly emphasizing the identification of phenotypic features (endophenotypes or biomarkers) to delineate subgroups that could predict outcomes and direct treatment choices [Viding & Blakemore 2007]. The terms “endophenotypes” and “biomarkers” imply that these neurophysiologic, biochemical, endocrinologic, neuroanatomic, and cognitive features are more biologic and, thus, more proximally related to the underlying etiologic processes than the behavioral symptoms [Gottesman & Gould 2003].

The following phenotypes have been investigated:

• IQ scores in longitudinal studies strongly predict long-term outcomes and are directly associated with the degree of autistic psychopathology even in young children [Lord et al 2001, Howlin et al 2004, Chawarska & Bearss 2008]. Stevens et al [2000] reported that early normal or near-normal nonverbal IQ is the best predictor of adequate functioning by grade school; however, in the presence of significant language addition, uneven cognitive profiles typical of autism may make an average of widely discrepant scores meaningless [Klin et al 2005a]. That said, 50% to 70% of autistic children have historically been classified as intellectually disabled by nonverbal IQ testing [Fombonne 2005, Baird et al 2006]. An epidemiologic study from the Centers for Disease Control and Prevention reported 44.6% of the ASD population had intellectual disability. Lower rates of intellectual disability reported in more recent studies are probably the result of broadening of the ASD diagnostic criteria to include Asperger syndrome and children with milder symptoms [Autism and Developmental Disabilities Monitoring Network 2009].
• Seizures develop in approximately 25% of children with autism. In addition, the rate of electroencephalographic abnormalities is increased in children with autism who do not have a history of seizures [Kim et al 2006, Spence & Schneider 2009]. As in the general population, seizures alone are not a sensitive predictor of outcome. However, the prevalence of seizures is higher among individuals with moderate to severe intellectual disability and those with motor deficits [Tuchman & Rapin 2002]. And individuals with autism plus epilepsy have on the average lower IQs and poorer adaptive, behavioral, and social outcomes than those without epilepsy [Hara 2007].
• Structural brain malformations, typically identified by MRI, usually portend a poorer outcome [Miles & Hillman 2000]. In a recent study of 77 children with autistic disorder of unknown cause and uncomplicated by seizures, severe intellectual disability, major anomalies, or focal neurologic signs, neuroradiologists reported that 40% had some abnormality, of which white-matter signal abnormalities, severely dilated Virchow-Robin spaces, and temporal lobe structural abnormalities were the most common [Boddaert et al 2009]. This level of pathology in children with nonsyndromic autism lends support to the controversial recommendation to obtain brain MRIs as a standard diagnostic test in autism.
• Significant generalized dysmorphology, found in 15% to 20% of individuals with autism, is a reliable indicator of an insult to early development [Miles & Hillman 2000]. Using a classification system that defines generalized dysmorphology, Miles et al [2005] found that in 81% of individuals dysmorphology was predictive of a poor outcome (defined as nonverbal with IQ <55). The presence of significant dysmorphology was also the top predictor of a poor response to early intensive behavioral therapy [Stoelb et al 2004]. The Autism Dysmorphology Measure (ADM), which guides clinicians through an assessment of 12 body areas, was developed to provide non-geneticists with a standardized method for assessing generalized dysmorphology [Miles et al 2008]. The 12 areas assessed are: height, hair growth pattern, ear structure, size and placement, nose size, face size and structure, philtrum, mouth and lips, teeth, hand size, fingers and thumbs, nails, and feet.
• Microcephaly (head circumference <2nd centile) occurs in 5%-15% of children with autism [Fombonne et al 1999, Miles et al 2000, Miles et al 2005] and is highly predictive of poor outcome.
• Macrocephaly (head circumference greater than the 97th centile), found in approximately 30% of children with autism, does not strongly correlate with outcome or IQ [Miles et al 2000] though Lainhart noted an association with delay in acquisition of first words [Lainhart et al 2006].

Using dysmorphology and microcephaly, autism can be defined as complex or essential [Miles et al 2005]:

• Complex autism is defined by the presence of dysmorphic features and/or microcephaly, features which indicate some alteration of early morphogenesis. Approximately 20%-30% of children ascertained because of a diagnosis of autism have complex autism. Complex autism is associated with a poorer prognosis, a lower male-to-female ratio, and a lower sibling recurrence risk than essential autism. Approximately 30% of children with complex autism can be diagnosed with an autism associated syndrome or chromosome disorder using currently available diagnostic tests (see Causes of Autism) [Miles et al 2008].
• Essential autism is defined by the absence of generalized dysmorphology and microcephaly. Approximately 70%-80% of children with autism have essential autism. Children with essential autism are more likely to be male, to have a higher sibling recurrence risk, and to have a greater family history of autism and autism-related disorders such as alcoholism and depression than children with complex autism. As a group, the outcome is better for essential autism than complex autism, though most children with essential autism still do poorly. Currently available testing is less likely to reveal an exact etiologic diagnosis in essential autism than in complex autism.

Establishing the Diagnosis

The American Psychiatric Association Manual of Psychiatric Diseases, 4th edition, is the primary diagnostic reference for autism used in the US. The update in 2000 changed some of the accompanying text but did not change the diagnostic criteria. (See American Psychiatric Association [2000].)

The DSM-IV in 1994 placed autistic disorder, Asperger syndrome, Rett syndrome, childhood disintegrative disorder, and pervasive developmental disorder-not otherwise specified (PDD-NOS) under the umbrella diagnostic term ‘pervasive developmental disorders.’ Subsequently, discovery of MECP2 mutations as the cause of Rett syndrome, uncertainty about nosology of childhood disintegrative disorder, and better understanding of the continuity within the autism diagnoses led to adoption of the term autism spectrum disorders (ASD) as the favored umbrella designation for autistic disorder (AD), Asperger syndrome (AS) and PDD-NOS (National Institute of Mental Health). It is expected that the DSM-V, due out in 2012, will further simplify the nosology.

Prevalence

An increase in the prevalence of all the autism spectrum disorders is being reported worldwide.

• Prior to 1990, most studies estimated a general population prevalence for autism of four to five per 10,000 (1/2000-1/2500) [Fombonne 2001].
• During the 1990s, studies of preschool children in Japan, England, and Sweden reported prevalence rates for autism of 21 to 31 per 10,000 (1/476 -1/323) [Arvidsson et al 1997, Baird et al 2000].
• A CDC case-finding study in Brick Township, New Jersey reported prevalence at 40 per 10,000 (1/250) for autism and 67 per 10,000 (1/149) for all PDDs [Autism and Developmental Disabilities Monitoring Network 2009].
• An epidemiologic study from the United Kingdom utilizing specialized visiting nurses who monitor child health and development at ages seven months, 18 to 24 months, and three years reported a prevalence rate of 16.8 per 10,000 (1/595) for autism and 63 per 10,000 (1/159) for all PDDs in children younger than age five years [Chakrabarti & Fombonne 2001]. Those rates were confirmed, reporting a prevalence rate of 22 per 10,000 (1/455) for autism and 59 per 10,000 (1/169) for all PDDs in children younger than age six years [Chakrabarti & Fombonne 2005].
• Two recent studies in the United States reported the diagnosis of an ASD in 1/91 children age three to seventeen years [Kogan et al 2009] and 1/110 children age eight years [Autism and Developmental Disabilities Monitoring Network 2009].

Recent analyses indicate that the “autism epidemic” does not reflect a true increase in the incidence of ASD, but is attributable to increased awareness by both the public and professionals, leading to more complete case finding together with broadening of the diagnostic criteria [Gernsbacher et al 2005, Fombonne et al 2006, Shattuck 2006, Taylor 2006, Atladottir et al 2007].

Studies finding the greatest increase in ASD also note lower rates of intellectual disability in these children. Only 30% of children with PDDs ascertained by Chakrabarti & Fombonne [2005] were intellectually disabled compared with 70% of children in earlier studies. This suggests that many of the higher-functioning children with milder autistic symptoms, such as less severe language impairment and fewer aggressive behaviors had not been counted in past epidemiologic surveys.

A recent update on the ongoing epidemiologic surveillance of autism in California indicated that the rise of autism in California shows no sign of plateauing. The study concluded that earlier age at diagnosis and inclusion of milder cases accounted for more than two-thirds of the increase but stated that the extent to which the continued rise could represent a true increase in the occurrence of autism remains unclear [Hertz-Picciotto & Delwiche 2009].

Genetic Causes

Known genetic causes of autism include:

• Cytogenetically visible chromosomal abnormalities (~5%)
• Copy number variants (CNVs) (i.e., submicroscopic deletions and duplications) (10%-20%)
• Single gene disorders in which neurologic findings are associated with ASD (~5%)

Environmental Causes

The search for environmental causes of autism has been driven by the considerable increase in autism prevalence recorded over the last 20 years and the incomplete concordance for autism in monozygotic (MZ) twins.

In utero exposures, including valproic acid, thalidomide, and misoprostol (an abortifactant commonly used in South America) are recognized causes of autism. The Liverpool and Manchester Neurodevelopment Group recently reported a long-term study of 632 children exposed to antiepileptic drugs (AEDs) during gestation and found that children exposed to valproate in utero were seven times more likely to develop autism than those not exposed to AEDs. None of the families had a known family history of autism. They recommend that women taking valproate be informed of the risk for autism in children exposed during gestation [Bromley et al 2008].

Other factors that have been considered as causes of autism include expanded use of assisted reproductive technologies (ART) [Knoester et al 2007] and tocolytic drugs such terbutaline [Connors et al 2005].

Childhood immunizations given around the time that regressive-onset autism is recognized have been a focus of concern. Organic mercury, which constitutes roughly 50% of the preservative thimerosal used in certain injectable vaccines, and the measles-mumps-rubella (MMR) vaccine, which never contained mercury, have been studied. Though parental concern is still significant, multiple studies and lines of scientific evidence have identified no support for a relationship between immunizations and autism [DeStefano & Thompson 2004, Institute of Medicine 2004, Taylor 2006, Schechter & Grether 2008]. The original studies by Wakefield et al [1998] and Wakefield [1999] suggesting an associated between immunizations and autism have been disproved and the work was retracted by the journal The Lancet [Murch et al 2004]. One of the tragedies resulting from fear of an autism epidemic was the decreased use of childhood immunizations leading to out outbreaks of measles and childhood deaths [Jansen et al 2003, Offit 2008].

Multifactorial Inheritance

The heritability estimate of autistic disorder, calculated from recurrence risk data and monozygotic (MZ): dizygotic (DZ) twin concordance data, is more than 90%. Many have considered autism of unknown cause a multifactorial disorder based on the: (1) high heritability, (2) failure to identify major autism genes, (3) 4:1 male-to-female sex ratio, and (4) sibling recurrence risk of approximately 4% [Chakrabarti & Fombonne 2001, Gillberg et al 2001].

The multifactorial threshold model predicts that:

• The more frequently affected sex (male) has a lower recurrence risk than the less frequently affected sex (female).
• The less often affected sex (female) is more severely affected than the more often affected sex (male).

Studies indicate that autism does not follow this model:

• Sibs of male and female probands with autism of unknown cause have the same risk of developing autism [Miles et al 2004].
• The proportion of relatives with a mild subclinical autism phenotype, defined as increased impulsivity, aloofness, shyness, over-sensitivity, irritability, eccentricity and anxiety, is not increased when the proband is female [Pickles et al 2000].
• When analyses are limited to probands with essential autism, females have less severe autistic symptoms than males [Miles et al 2004].

Lack of support for the classic multifactorial threshold model, however, does not eliminate the possibility that many genes are involved in autism. Instead, it suggests that genetic heterogeneity is the main impediment to understanding the inheritance of autism.

Genes that Cause or Increase the Risk of Autism

Determining specific genetic changes that increase the risk of developing autism is an area of intense study. The large-scale genetic studies of the last decade have ruled out the possibility that single gene of large affect causes a high proportion of autism. Rather it appears that a a significant number of highly penetrant autism alleles will be discovered in families. Study of these rare alleles will be essential to elucidating the pathogenetic mechanisms involved in the development of autism.

Array CGH has increased detection of copy number variants (CNVs) in autism and paved the way for identification of a number of new autism genes [Szatmari et al 2007]. Some CNVs may help identify highly penetrant causal mutations, while others may lead to the discovery of multiple common genetic variations which act in concert, possibly with environmental triggers to cause autism. Persuasive evidence for this common disease-common variant hypothesis in autism includes the presence of subtle sub-clinical autism symptoms in relatives of children with autism [Constantino et al 2009]. It is also probable that some CNVs may alter the expression of genes in the immediate vicinity of the CNV.

Table 1 which lists known and putative autism genes is unquestionably incomplete, as new candidate genes are being reported at an unprecedented rate. The genes are organized by pathogenesis to highlight the progress made in the functional assessment of autism candidate genes and pathways. In addition, some genes are included because of their compelling initial descriptionsthat still await confirmation. Selected references address both molecular and pathophysiologic descriptions.

Authoritative reviews of the current status of candidate genes and loci include: Veenstra-VanderWeele & Cook [2004], Wassink et al [2004], Grice & Buxbaum [2006], Gupta & State [2007], Szatmari et al [2007], Morrow et al [2008], O’Roak & State [2008], Sutcliffe [2008], Simons Foundation [2009].

SFARI gene is a new comprehensive, Web-based, searchable list of candidate genes associated with ASD. The candidate genes are richly annotated for their relevance to autism, along with an in-depth, up-to-date view of their molecular function extracted from the current scientific literature.

The Genetic Association Database provides online access to human genetic association studies performed on autism and other complex disorders.

Mode of Inheritance

Genetic counseling for families of probands with a chromosomal disorder, copy number variant, or a single gene disorder is based on information relevant to the primary diagnosis.

The mode of inheritance for autism of unknown cause is not known.

Risk to Family Members—Autism of Unknown Cause

Parents of a proband. No data on the risk to parents of a proband of having autism of unknown cause are available; however, parents of children with an ASD are more likely to exhibit mild autistic phenotypes, such as social awkwardness and a variety of psychiatric disorders including alcoholism, depression, obsessive-compulsive disorder, and panic and anxiety disorders when compared to parents of children with non-ASD disorders such as Down syndrome [Piven & Palmer 1999, Miles et al 2003, Wilcox et al 2003, Lauritsen et al 2005, Yirmiya & Shaked 2005]. In several studies rates of 10%-45% for social impairment, aloofness, shyness, and pragmatic language impairment were present in at least one parent of children with autism spectrum disorders [Freitag 2007]. Cederlund & Gillberg [2004] reported that 70% of probands with autism of unknown cause studied had a first- or second-degree relative with autistic symptoms, and that 15% had fathers with Asperger syndrome.

Sibs of a proband. The empiric aggregate risk to sibs of individuals with autism of unknown cause varies across studies but is generally considered to range from 5% to 10% for autism and 10% to 15% for milder symptoms, including language, social, and psychiatric disorders [Bolton et al 1994, Lauritsen et al 2005, Miles et al 2005, Landa 2008, Selkirk et al 2009]. For families with two or more affected children, the recurrence risk approaches 35% [Ritvo et al 1989]. No recurrence risk data are available for families who have one autistic child plus another child or relative with mild autistic symptoms. Therefore, the amount of weight to put on mild autistic symptoms in siblings, parents, and other relatives when estimating recurrence risk for families is unknown.

• Essential autism
  • Male sibs (brothers) of a proband with essential autism have a 7% risk for autism and an additional 7% risk for milder autism spectrum symptoms [Miles et al 2005].
  • Female sibs (sisters) of a proband with essential autism have a 1% risk for autism. The risk for milder autism spectrum disorder is unknown [Miles et al 2005].
• Complex autism. The recurrence risk to sibs of a proband with complex autism is 1% for autism and an additional 2% for milder autism spectrum symptoms [Miles et al 2005].

Offspring of a proband. No data are available.

Related Genetic Counseling Issues

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Prenatal testing for families at risk of having a child with a chromosomal disorder, copy number variant, or a single gene disorder known to be associated with autism may be available for the specific etiology.

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with autism, the following evaluations are recommended:

• Medical evaluation. A complete medical evaluation and review of systems to assess growth and identify health problems that may interfere with optimum development and progress. In particular, note:
  • Sleep. Problems falling asleep, early or mid-night wakening and parasomnias are common. Routine sleep hygiene recommendations, search for underlying physical causes, and referral to sleep specialists are warranted. Medications should be delayed until underlying causes are ruled out.
  • Gastrointestinal symptoms including both constipation and diarrhea are common in autism and respond to medical management. Referral to a gastroenterologist is recommended if symptoms are chronic
  • Obesity. Children with autism are often treated with medications, such as atypical antipsychotics which can increase hunger and lead to weight gain. In addition, many children and teenagers are physically inactive, preferring the computer and video games.
  • Hearing evaluation
• Neurologic dysfunction. Signs of seizures, focal neurologic deficits
• Cognitive testing. A cognitive assessment by a psychologist experienced in autism evaluations; however, since IQ scores may change especially in young children it is recommended that children be retested every three years. This is usually done through the school system and those records should be obtained.
• Language/communication assessment. Assess whether the child is functionally verbal or only has occasional words or echolalia. Language assessment by a trained speech/language pathologist with access to training modalities and communication modalities such as Picture Exchange Communication System (PECS). Even children who appear functionally verbal generally need ongoing speech and language therapy to gain skills in pragmatics and social and receptive communication.
• Behavioral evaluation. Assess for repetitive behaviors, aggression, self-injurious behavior, mood, and anxiety.
• Educational programs and interventions. Assess adequacy and progress.
• Family functioning, including financial resources including qualifications for Medicaid, Social Security Supplemental Income, and other state specific programs

Treatment of Manifestations

Optimally, an autism intervention program uses an experienced team of medical, behavioral, and educational specialists. Working with an established team is easiest for families; however, many physicians and families have successfully assembled programs that work well.

Early diagnosis and early intensive behavioral therapy are essential to an optimal outcome. Two comprehensive treatment reviews are Educating Children with Autism [Lord et al 2001] and Management of Children with Autism Spectrum Disorders from the American Academy of Pediatrics [Myers & Johnson 2007] are both available online. Also recommended is an evaluation of single-subject studies to determine which educational practices meet the criteria of "evidence-based practice" [Odom et al 2003].

Surveillance

Children with autism should be followed at least annually to monitor health, educational, language, and behavioral progress. An update of the areas covered in the initial evaluation is recommended. Identification of specific complications is a targeted goal of the Autism Treatment Network, which will be following a large cohort of individuals into adulthood. Since diagnostic and treatment recommendations will continue to be revised, periodic diagnostic reappraisals by a medical geneticist or an autism center are recommended. As more individuals receive etiologic diagnoses, diagnosis-specific surveillance profiles will be developed.

Complications for which evidence supports routine monitoring include:

• Seizures
• Sleep disturbances
• Feeding problems
• Gastrointestinal symptoms
• Medication-specific side effects
• Mood and psychiatric dysfunction
• Medication-induced complications. All children on medications should be closely monitored for medication side effects.

Agents/Circumstances to Avoid

A hands-off or wait-and-see approach should be avoided because children with autism are unlikely to be able to navigate the social world and develop reciprocal communication skills without intensive therapeutic intervention.

Families need to be cautioned about unproven and potentially dangerous “alternative therapies” that may be promoted either by well-meaning but naïve people or by unscrupulous groups, individuals, or clinics.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

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Suggested Reading

1. Attwood T. The Complete Guide to Asperger's Syndrome. London: Jessica Kingsley Publishers, Ltd; 2007.
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4. Immunization Safety Review Committee, Stratton K, Gable A, Shetty P, McCormick M, eds. Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. Washington, DC: The National Academies Press. Available at books​.nap.edu. 2010. Accessed 4-10-10.
5. McAfee J. Navigating the Social World: A Curriculum for Individuals with Asperger's Syndrome, High Functioning Autism and Related Disorders. Arlington, TX: Future Horizons; 2002.
6. National Institute of Mental Health. Autism Spectrum Disorders: Pervasive Developmental Disorders. Available in pdf. 2004. Accessed 4-10-10.

Revision History

• 13 April 2010 (me) Comprehensive update posted live
• 1 December 2005 (me) Comprehensive update posted to live Web site
• 27 August 2003 (me) Overview posted to live Web site
• 8 July 2002 (jm) Original submission