Pediatric Annals

CME Article 

Diagnosis of Autism Spectrum Disorders

Karen Toth, PhD; Gary Stobbe, MDN


The Centers for Disease Control and Prevention estimates that one in 110 children in the United States has autism spectrum disorder.1 During the past decade, the prevalence of autism has increased by almost 300%.


The Centers for Disease Control and Prevention estimates that one in 110 children in the United States has autism spectrum disorder.1 During the past decade, the prevalence of autism has increased by almost 300%.

Both authors are affiliated with University of Washington and Seattle Children’s Hospital, Seattle, WA. Karen Toth, PhD, is Assistant Professor, Department of Psychiatry and Behavioral Sciences. Gary Stobbe, MD, is Clinical Assistant Professor, Departments of Neurology and Psychiatry and Behavioral Sciences.

Drs. Toth and Stobbe have disclosed no relevant financial relationships.

Address correspondence to: Karen Toth, PhD, 4800 Sand Point Way NE, Seattle, WA 98105; email:

The Centers for Disease Control and Prevention estimates that one in 110 children in the United States has autism spectrum disorder.1 During the past decade, the prevalence of autism has increased by almost 300%.1

This appears to be caused largely by the loosening criteria for autism spectrum disorder (ASD) in the Diagnostic and Statistical Manual of Mental Disorder (DSM), third edition (DSM-III) to fourth edition (DSM-IV), and increased public awareness; for example, the US special education classification for autism was not introduced until 1994.2

ASDs affect more males than females, with an average male-to-female ratio of 4.3:1. For children who have both autism and intellectual disability the male-to-female ratio is closer to 2:1, and the ratio without intellectual disability is closer to 5.5:1.2

Autism is a highly heritable disorder with a complex inheritance pattern. A polygenic, multifactorial inheritance model is the current best fit for understanding the genetics of non-syndromic forms of autism (ie, most cases).

Besides mapping a large number of risk alleles, researchers are also investigating new mutations and epigenetic mechanisms (genetic imprinting or epimutations that trigger the underlying susceptibility).3

Other risk factors and markers being researched include infection and immune dysfunction; neuropeptides, such as oxytocin and vasopressin; endocrine and obstetric factors; and exposure to drugs, metals, and other toxins.2 Numerous independent investigations have failed to confirm an association between the measles, mumps, and rubella (MMR) vaccine specifically, or thimerosal exposure to environmental mercury, and autism.

DSM-IV Diagnostic Criteria

Autistic Disorder

Autistic disorder is characterized by impairments across three domains of functioning: reciprocal social interaction; communication; and restricted, repetitive, and stereotyped interests and behaviors. For a diagnosis of autistic disorder according to DSM-IV, there must be at least six total symptoms with impairments in all these domains: at least two social symptoms; one communication symptom; and one symptom of repetitive, stereotyped interests and behaviors. Symptoms must be present by age 3 and not better accounted for by either Rett disorder or childhood disintegrative disorder.

Asperger’s Disorder

The primary diagnostic distinction between Asperger’s disorder and autistic disorder is the absence of early language delays (ie, single words by age 2, phrases by age 3) and no clinically significant delays in cognitive or adaptive functioning. Language anomalies, including deficits in pragmatic language and use of stereotyped language, are not regarded as delays in this context. There must be at least two or more social symptoms and at least one symptom in restricted, repetitive, and stereotyped interests and behaviors for the diagnosis of Asperger’s disorder. However, if a child meets the criteria but exhibits six or more symptoms across all three domains of functioning, the more appropriate diagnosis is autistic disorder. In fact, there is little empirical support for a diagnostic distinction between higher functioning individuals with autistic disorder and those with Asperger’s disorder in clinical presentation or outcome.4DSM-5 is planning to eliminate Asperger’s disorder as a distinct diagnostic category.

Pervasive Developmental Disorder-Not Otherwise Specified

This diagnostic category of Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) is used more often than the other ASD diagnoses,5 but is the most poorly defined. It is reserved for individuals who demonstrate clinically significant symptoms across at least two domains of functioning but do not meet criteria for either autistic disorder or Asperger’s disorder. A recent comparison of individuals based on autism symptomatology showed that those with PDD-NOS exhibit a distinct pattern of symptoms in social reciprocity and communication, but not repetitive and stereotyped behaviors.5

Proposed DSM-5 Changes

Changes proposed for DSM-5 include combining autistic disorder, Asperger’s disorder, and PDD-NOS into a single category of autism spectrum disorder.6 Another diagnostic category — social communication disorder (SCD) — will be used to describe pragmatic communication disorders once ASD has been ruled out.

Additionally, the three symptom domains in DSM-IV will merge into two: 1) social communication; and 2) restricted interests and repetitive behaviors. Sensory symptomatology, currently considered when evaluating children for an ASD, will now be specified in the diagnostic criteria, per proposed DSM-5 changes. New specifiers and modifiers are also being proposed, such as “ASD with intellectual disability.”

Diagnostic Stability

When children are diagnosed by expert clinicians between the ages of 2 years to 9 years, the diagnosis of autistic disorder was reliable and stable.7 Some children diagnosed with PDD-NOS by experts at age 2 years moved to a diagnosis of autistic disorder by age 9 years, indicating that the diagnosis of PDD-NOS is less stable over time than autistic disorder. Still other studies have shown that instead of moving to autistic disorder, some children with early diagnoses of PDD-NOS move off the spectrum entirely at follow-up.8

Clinical Presentations

Social Impairments

Primary deficits in social attention and social reciprocity characterize all three categories of ASD. Impairments in looking at others and orienting to name have been shown to distinguish infants with autism from those with typical and delayed development as early as 8 months of age.9 Joint attention (eg, pointing to show something to another, following another’s eye gaze, or pointing to an object), which develops typically between 9 and 12 months of age and is important for language development, is impaired in children with autism. Other early impairments occur in motor imitation, social imitative play (eg, peek-a-boo), visual tracking and disengagement of visual attention, among others.10

Communication Impairments

Language and communication skills development in individuals with autism is often delayed and/or atypical. As many as 40% of individuals never acquire spoken language,11 while others exhibit unusual prosody of speech (eg, too loud, too quiet, odd intonation or stress, too fast or too slow); echolalia (ie, repeating words and phrases either immediately after hearing them or after a delay; includes repeating phrases from movies), pronoun reversal (eg, saying “you want” instead of “I want”), and pragmatic communication impairments, most often noticeable in open-ended conversation (eg, difficulties with staying on topic, responding to nonverbal cues, and reciprocity). Symbolic play, which is also related to language and communication abilities, is often absent, delayed, or repetitive in children with autism.

Restricted, Repetitive, Stereotyped Behaviors and Interests

Symptoms in this domain are quite often absent or go unnoticed in very young children with autism (ie, age 2 years and younger), but may emerge later. Therefore, the absence of these symptoms early on does not preclude an ASD diagnosis. Common behaviors in this category include motor stereotypies (ie, repetitive movements or utterances), both with the hands and the whole body (eg, repetitive hand flapping, finger flicking, spinning, pacing); repetitive use of objects or preoccupation with parts of objects (eg, opening and closing the door on a toy vehicle, lining up objects, turning a car over and focusing on spinning the wheels); unusual interests (eg, interest in washing machines) and/or all-consuming interests (eg, a young child who has books on trains, videos on trains, toy trains, talks only about trains, etc.); and compulsive, rigid, ritualistic behaviors (eg, wanting things to be in a certain order, needing to drive the same route every day, insisting on sameness, etc).

Onset and Course

Historically, autism was thought to emerge either early in the first year of life, or in the second year after a period of fairly typical development and then a regression of previously acquired skills (still reported in roughly 20% to 30% of cases).12 Newer research suggests a number of patterns of emergence, including cases that involve early symptoms and later regression, as well as cases of developmental plateau, and failure to progress.13

The earliest emerging symptoms of autism (ie, evident by 8 to 12 months) include failure to respond when called by name (lack of social orienting, not orienting to faces), joint attention impairments (not showing or pointing out objects to others), and fewer vocalizations, among others. Parents do not always notice these early symptoms, particularly for firstborn babies, but they can be assessed quickly and easily within the context of a medical visit.


Outcomes for individuals with autism have been measured in many different ways, using variables such as cognitive ability, vocation, relationships, adaptive functioning, and the ability to live independently. The two best predictors of positive outcomes for youth with autism are IQ above 50 and spoken language by age 5 years.14 Clearly, short-term outcomes improve with earlier diagnosis and treatment15 However, more than half of all individuals with ASD have poor long-term outcomes, based on occupation, friendships, and adaptive living skills. Adaptive functioning often is impaired, even in children and adolescents with higher IQs. Adaptive skills, however, are not generally a focus of treatment for these higher-functioning children.

Little is known regarding the outcome of adults with ASD. Most studies have focused on functional outcomes and quality of life and have demonstrated persistent difficulties in multiple domains even among “higher-functioning” ASD individuals (ie, those with IQs above 70).16 At the same time, as many as 10% to 20% of individuals can make substantial gains to the point of no longer meeting criteria for an autism spectrum diagnosis.13 Much research remains to be done regarding adult outcomes, including on how intensive early behavioral intervention affects outcomes.

Psychiatric Comorbidities

Intellectual Disability

A decade ago, two-thirds of children with autism also had intellectual disability (mental retardation). Current estimates place that number at 40% to 55%,2 because of increased awareness, expansion of the diagnostic criteria, and a greater number of individuals identified with more subtle but still impairing symptoms.

Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is highly comorbid with autism; as many as 55% of children with autism can also meet diagnostic criteria for ADHD.17

Anxiety Disorders

Symptoms of anxiety are common in children with autism at all levels of functioning and are often related to sudden changes in routine and a lack of predictability in daily living. Overall, an anxiety diagnosis has been found in 42% to 55% of youth with autism, which most commonly includes simple phobias, separation anxiety, and generalized anxiety.18

Mood Disorders

Individuals who are higher-functioning are particularly prone to developing symptoms of depression, which can include irritability, aggressive behaviors, and isolation. Roughly 10% to 24% of youth with ASD meet criteria for major depression.17

Tourette’s Syndrome

Approximately 11% of children with autism also meet diagnostic criteria for Tourette’s syndrome.19

Sensory-Based Behaviors

Characterized as either heightened sensitivity (to light, sound, or touch) or sensory-seeking (eg, prolonged oral, visual, or tactile exploration; seeking deep pressure on one’s body), time spent on these behaviors can be significant and cause considerable impairment in daily living.

Self-Injurious Behaviors

Although not specific to ASD, self-injurious behaviors are common in children with autism, particularly those with more severe symptoms as well as cognitive impairment.

Medical Comorbidities


The reported prevalence of epilepsy (recurrent, unprovoked seizures) in autism has ranged from 5% to 46%.20 The age of seizure onset has followed a bimodal distribution, with one peak at younger than age 6 years, and a second peak in adolescence. Seizure type varies from generalized seizures (eg, infantile spasms, generalized tonic-clonic) to partial-onset seizures, the most common type in autism. Epilepsy in autism tends to correlate with intellectual disability and a worse prognosis, supporting the concept of a more severe underlying neurological process (“autism plus”). Because certain types of seizures (eg, complex partial) can be difficult to recognize in the autism population, seizures should be considered in the differential diagnosis of a new, unexplained behavioral disturbance or developmental regression after the age of 4 years.

Sleep Disorders

Sleep disorder is the most common medical comorbidity in the autism population, seen in an estimated 50% to 80% of patients.21 Disturbance of sleep onset and sleep maintenance are common, and can result in worsening of the individual’s daytime functioning, while also disrupting family stability. Primary sleep disorders, such as restless legs syndrome (sometimes caused by an iron deficiency) and obstructive sleep apnea (commonly caused by enlarged tonsils and adenoids), can be seen in ASD, as well as sleep disruption secondary to other medical conditions, such as nocturnal seizures and gastroesophageal reflux. A sleep study should be considered if sleep hygiene and behavioral strategies are ineffective.

Nutrition and Gastrointestinal Dysfunction

The relationship of gastrointestinal (GI) dysfunction and ASD is controversial. Many complementary and alternative medicine therapies have targeted GI health, some based on theories that GI dysfunction is not only associated with autism, but possibly causative. These theories have been supported primarily by anecdotal evidence, and have not held up to more rigorously designed studies. Data have supported a higher incidence of constipation and food selectivity in the ASD population, although the underlying basis of these symptoms is more likely behavioral than biological.22 GI health and overall wellness should not be ignored; physical symptoms and nutritional deficiencies can be difficult to recognize and diagnose in this population, and could worsen autistic behaviors.

Assessment and Diagnosis

Primary Care Provider Assessment

The following probes for assessing early symptoms are the same as those used in standardized diagnostic instruments, such as the Autism Diagnostic Observation Schedule;23 however, they take only a few minutes to administer and observe, making them easy to include in well-child exams.

Eye contact and social orienting can be assessed at most every well-child check. Neonates orient to faces and show a preference for faces over objects. Observe the infant during interactions with mother and provider and note whether the infant orients to the face.

Response to name, imitative social play, and social smiling can be assessed later in the first year of life. Within the first few minutes of the exam, move to a location behind the infant and call the child’s name several times. Engage the child socially by smiling and peeking at the infant from behind an object. Observe the infant for smiling, cooing, turning to look at the provider when called by name, making eye contact throughout, and showing enjoyment and anticipation during peek-a-boo.

Vocalization and gesture use, motor imitation, and joint attention can be assessed starting at the 12-month visit. Note use of speech-like babble and word approximations, social use of gestures (waving goodbye), imitation of simple motor actions (sticking your tongue out, clapping), and ability to follow your point.

Referral to a developmental clinic and early intervention program may be warranted if delays are noted in these skill domains.

Screening Instruments

Reliable screening instruments for children in the first year of life are still being researched. For children younger than 16 months, providers should follow the Centers for Disease Control and Prevention Act Early guidelines.24 All children 16 months and older should be screened with the Modified-Checklist for Autism in Toddlers (M-CHAT), a 23-item yes/no parent checklist.25 For children 4 years and older, the Social Communication Questionnaire (SCQ), a short parent-report questionnaire, is recommended.26

Evidence-Based Assessment

A comprehensive assessment begins with the pediatrician/family physician screening for autism symptoms in the primary care setting. When feasible within a local health care system, positive screens can be followed by referral to a specialty clinic for detailed diagnostic assessment using standardized tools, such as the Autism Diagnostic Interview-Revised (ADI-R)27 and the Autism Diagnostic Observation Schedule (ADOS),23 and screening for psychiatric and behavioral conditions common in youth with ASD. Confirmed autism diagnoses can be followed by a speech and language evaluation, an occupational and/or physical therapy assessment (to address motor delays and sensory based behaviors), and social work evaluation (to assess family functioning and resources). A neuropsychological examination may also be requested to formally assess cognitive, memory, executive functioning, and academic skills, and to provide recommendations for educational programming, especially in older children and adolescents.

Medical Assessment and Follow-up

If a child is being considered for ASD diagnosis, the evaluation should include a neurodevelopmental examination and a hearing evaluation. Once a diagnosis has been established, genetic testing to rule out Fragile X syndrome is recommended if comorbidity with intellectual disability is suspected.28 Additional assessment, such as more detailed genetic and metabolic testing, neuroimaging, and electroencephalography (EEG) should be considered on an individualized basis. Medical follow-up is also tailored for the individual, and may include involvement from multiple specialties (developmental pediatrics, neurology, psychiatry, and genetics) in addition to the primary care provider.


As autism researchers advance understanding of genetic and environmental risk factors for ASD, recognized cases of autism continue to increase, and our behavioral definition of the disorder continues to evolve. Screening and diagnostic tools are now available; children are being identified at very early ages, and then entering early intervention programs. Primary care providers are critical to the process of detecting early signs and symptoms of ASD and referring patients for further evaluation.


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CME Educational Objectives

  1. Know the evolving behavioral definition of autism spectrum disorder (ASD).

  2. Provide diagnostic criteria for autism spectrum disorders highlighting clinical presentation and course, comorbid disorders, and behaviors common to ASD.

  3. Determine an evidence-based approach to assessment, including tools that are ideal for use in the primary care setting.


Both authors are affiliated with University of Washington and Seattle Children’s Hospital, Seattle, WA. Karen Toth, PhD, is Assistant Professor, Department of Psychiatry and Behavioral Sciences. Gary Stobbe, MD, is Clinical Assistant Professor, Departments of Neurology and Psychiatry and Behavioral Sciences.

Drs. Toth and Stobbe have disclosed no relevant financial relationships.

Address correspondence to: Karen Toth, PhD, 4800 Sand Point Way NE, Seattle, WA 98105; email:


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