Key points

There has been a significant increase during the past decade in the number of children diagnosed with autism spectrum disorders (ASD). A disorder once thought to be exceedingly rare is now estimated to affect 1 in 45 (2.2%) US children. Public awareness campaigns by advocacy groups, testimonials by celebrities with affected children, and increased funding for treatment programs and research have also contributed to parents’ and professionals’ better recognition of children with this condition. However, concerns have been raised about the accuracy of the prevalence figures and the dramatic increase in autism diagnoses over time.

Most neurodevelopmental and behavior disorders are defined by their clinical symptoms and many disorders share common features. The key to accurate differential diagnosis is identifying the core, or essential, symptoms that help distinguish one condition from others that have overlapping symptom manifestations. No single behavior or category of behavior is characteristic (pathognomonic) of ASD. To the contrary, there is evidence that some of the central features of ASD are fractionable (ie, they occur individually at fairly high frequency in the normal population even to the extent seen in individuals with ASD). A further complication arises with the use of the term “spectrum.” The American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) clearly intended use of this term as a way to account for differences in symptom severity between individuals, and changing manifestations related to developmental level and chronologic age. Thus, it is often the unique clustering of symptoms that defines a specific disorder.

This article provides information about ASD and other disorders that share common symptoms that should be considered as part of the differential diagnosis of a child with a developmental disorder ( Box 1 ). It is not sufficient when screening children with early signs of ASD to simply rule in or rule out an ASD diagnosis. The screening must encompass consideration of which diagnoses could best account for the child’s symptoms and what interventions or treatments will be most effective.

Autism spectrum disorder

The most recent revision of the DSM-5 identifies two core domain deficits in ASD. The first involves a persistent impairment in social communication and social interaction across multiple contexts. Individuals with ASD have significant difficulty in three areas of social functioning: (1) social-emotional reciprocity; (2) using nonverbal communicative behaviors for social interaction; and (3) developing, maintaining, and understanding relationships. DSM-5 specifies that deficits must be present in all three areas. The second domain involves restricted, repetitive patterns of behavior, interests, or activities (RRBIs) manifesting in at least two of the following categories of behavior: stereotyped or repetitive motor movements, use of objects, or speech; insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior; highly restricted, fixated interest that are abnormal in intensity or focus; and hyperactivity or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment. RRBIs must be present in the early developmental period, but may not become fully manifest until social demands exceed a child’s capacity for interaction.

One of the earliest signs of the social deficit characteristic of ASD is impairment in joint attention behaviors that typically appear by 8 to 9 months of age. Joint attention involves sharing experiences, emotions, and intentions with another person through the use of gaze, gestures, and vocalizations. DSM-5 includes this under “deficits in nonverbal communicative behaviors used for social interactions.” Other striking characteristics of children with ASD include deficits in imitation and pretend play that are out of proportion to the child’s nonverbal cognitive ability. Like joint attention, imitation and pretend play are linked to the concept of “theory of mind,” which is the capacity to understand what another person is thinking and feeling, and to react and adapt to that person’s needs and desires.

Approximately one-third of children diagnosed with ASD have a history of developmental regression occurring between 15 and 30 months of age. The change may be abrupt or slow and insidious, occurring over the course of days or weeks. Loss of previously acquired language skills is accompanied by regression in social skills and the appearance of behaviors that are associated with ASD: decreased eye contact; loss of social smile and interest in others; and the onset of hyperactive, perseverative, and stereotypic behaviors. In some children, slow and incomplete recovery may follow, but long-term outcome is generally poor. No specific cause or explanation for this phenomenon has been identified.

The cause of ASD is multifactorial. Most evidence suggests that it is a structural and functional brain disorder with a strong genetic basis. Nonetheless, proximal causes may include premature birth, known genetic and metabolic disorders ( Box 2 ), and as yet unspecified environmental influences on gene expression. A world survey of ASD identified a strong (81%) male predominance.

Several prospective longitudinal studies have documented the persistence of symptoms of ASD over childhood, particularly in the domain of social communication and social interaction. In some instances, symptoms of RRBIs may diminish with increasing age. Clinical improvement is often associated with increased communication ability. There are also well-documented reports of children who have recovered from ASD.

Autism spectrum disorder

The most recent revision of the DSM-5 identifies two core domain deficits in ASD. The first involves a persistent impairment in social communication and social interaction across multiple contexts. Individuals with ASD have significant difficulty in three areas of social functioning: (1) social-emotional reciprocity; (2) using nonverbal communicative behaviors for social interaction; and (3) developing, maintaining, and understanding relationships. DSM-5 specifies that deficits must be present in all three areas. The second domain involves restricted, repetitive patterns of behavior, interests, or activities (RRBIs) manifesting in at least two of the following categories of behavior: stereotyped or repetitive motor movements, use of objects, or speech; insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior; highly restricted, fixated interest that are abnormal in intensity or focus; and hyperactivity or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment. RRBIs must be present in the early developmental period, but may not become fully manifest until social demands exceed a child’s capacity for interaction.

One of the earliest signs of the social deficit characteristic of ASD is impairment in joint attention behaviors that typically appear by 8 to 9 months of age. Joint attention involves sharing experiences, emotions, and intentions with another person through the use of gaze, gestures, and vocalizations. DSM-5 includes this under “deficits in nonverbal communicative behaviors used for social interactions.” Other striking characteristics of children with ASD include deficits in imitation and pretend play that are out of proportion to the child’s nonverbal cognitive ability. Like joint attention, imitation and pretend play are linked to the concept of “theory of mind,” which is the capacity to understand what another person is thinking and feeling, and to react and adapt to that person’s needs and desires.

Approximately one-third of children diagnosed with ASD have a history of developmental regression occurring between 15 and 30 months of age. The change may be abrupt or slow and insidious, occurring over the course of days or weeks. Loss of previously acquired language skills is accompanied by regression in social skills and the appearance of behaviors that are associated with ASD: decreased eye contact; loss of social smile and interest in others; and the onset of hyperactive, perseverative, and stereotypic behaviors. In some children, slow and incomplete recovery may follow, but long-term outcome is generally poor. No specific cause or explanation for this phenomenon has been identified.

The cause of ASD is multifactorial. Most evidence suggests that it is a structural and functional brain disorder with a strong genetic basis. Nonetheless, proximal causes may include premature birth, known genetic and metabolic disorders ( Box 2 ), and as yet unspecified environmental influences on gene expression. A world survey of ASD identified a strong (81%) male predominance.

Several prospective longitudinal studies have documented the persistence of symptoms of ASD over childhood, particularly in the domain of social communication and social interaction. In some instances, symptoms of RRBIs may diminish with increasing age. Clinical improvement is often associated with increased communication ability. There are also well-documented reports of children who have recovered from ASD.

Primary communication disorders

Two types of primary communication disorders are confused with ASD and should be considered in a differential diagnosis: specific language impairment (SLI) and social (pragmatic) communication disorder (SPCD).

SLI often presents as delayed onset of expressive and receptive language abilities. Nonverbal cognitive abilities, social interactions, and play patterns are normal, and delayed verbal development is not caused by oral-motor or speech sound production deficits. Children with SLI are about 2 years delayed in onset of language development but then follow a similar rate of development as their typically developing peers, although they do not seem to catch up over time. Deficits in specific aspects of grammar, semantics, and conversational skills are characteristic of SLI and persist through adulthood. These lingering deficits often lead to academic, social, and adjustment disorders as children progress through school.

SPCD is a form of communication disorder that affects how language is used for social exchanges. This condition was first described in the 1980s as a higher-level language disorder affecting how words and gestures are used to mediate social interactions. Affected individuals have intact structural language abilities but struggle with practical and appropriate aspects of social communication. As described in DSM-5, individuals with SPCD may not know how to initiate conversations or may fail to follow rules of turn taking. They may not adapt their language to match the context or needs of their partner. For example, they may provide too little or too much background information. Additionally, they frequently have difficulty interpreting nonliteral or ambiguous language, such as idioms, humor, metaphors, sarcasm, irony, and so forth.

Communication ability appears as a fractionable component function in several neurodevelopmental disabilities. Thus, children diagnosed with ASD may have normal structural language abilities or present with a profile of deficits that is indistinguishable from SLI. Similarly, pragmatic deficits are seen in children without other features of ASD, and in individuals with attention-deficit/hyperactivity disorder, structural brain anomalies (hydrocephalus), and genetic disorders (Williams syndrome).

Anxiety disorders

Anxiety disorders are common in typically developing children and those with ASD. These disorders are characterized by persistent symptoms that are excessive or out-of-proportion to the situation. Several types of disorders are recognized including generalized anxiety disorder, social anxiety disorder, and panic disorder, and a variety of specific phobias. Lifetime prevalence of any type of anxiety disorder in children or adolescents is estimated to be 15% to 20%. Symptoms may be present early in life and manifest as disturbances of sensory regulation (excessive irritability, colic or feeding difficulty, overstimulation), or behavioral withdrawal. Behavioral inhibition (the tendency to exhibit quiet withdrawal in response to novel stimuli or strangers) is a temperamental trait seen in toddlers and is often predictive of social anxiety during adolescence. Inhibited children may avoid eye contact with others, display social avoidance with peers, and prefer to play alone.

Selective mutism is a unique and uncommon (prevalence 0.18%–1.9%) form of anxiety. Children affected avoid speaking with individuals outside of their immediate family circle. Symptoms appear between 2 and 4 years of age, and selective mutism is more common in boys. Many children are not identified until they enter school for the first time. Two-thirds of children with selective mutism have other symptoms of anxiety, and a strong history of “shyness” and anxiety is usually present in immediate and extended family members. Follow-up studies suggest that the mean duration of symptoms is about 8 years. Selective mutism may dissipate completely, but the persistence of communication problems is associated with elevated rates of school and psychiatric disorders even into adult years.

Anxiety disorders are also a common feature in children with ASD; the prevalence is approximately 42%. Communication difficulties and discomfort in social situations may lead to anxiety, because a child with ASD may be unable to express emotions or negotiate social interactions well. For example, children with ASD are often fearful of intense and unwanted stimulation from medical or dental visits. The sensory stimulation of sound and touch during these visits is most upsetting. Similarly, crowds or unfamiliar settings may trigger extreme reactions in this group of children. Increased stereotyped language (rumination) and stereotyped behaviors (RBBIs) often appear in response to anxiety and may have a soothing and stress relieving effect.