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Asperger Syndrome

Editor: Mohammed Molla Updated: 2/12/2024 6:15:15 AM


Asperger syndrome (AS) was first described by Hans Asperger in 1944 as the behavioral characterization of individuals with difficulties in communication and social interaction.[1] Since then, there has been considerable interest and debate surrounding AS. Although AS was introduced as a distinct diagnostic category in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-4, 1994), its diagnostic label was removed from the subsequent edition, the Diagnostic and Statistical Manual of Mental Disorders (DSM–5), almost two decades later. Instead, AS was incorporated into a broader category known as autism spectrum disorders (ASD).[2] This change reflected a growing recognition that autism encompasses a spectrum of experiences with varying degrees of severity and a wide range of associated characteristics.[3]

Autism spectrum disorders (ASD) encompass a range of neurodevelopmental conditions characterized by diverse degrees and manifestations. Typically emerging in early childhood, these disorders are marked by challenges in social communication and interaction and behavioral patterns that involve restricted interests and repetitive behaviors.[4][5] The changes made to the classification of ASD in DSM-5 sparked controversy regarding the loss of the distinct Asperger identity. This shift in classification continues to be a topic of debate within the literature, as discussions revolve around the formulation and inclusion of AS within the broader ASD framework.[6][7] Given the extensive historical background of AS, its distinct semiotics, and the relatively characteristic clinical presentations, specialists still utilize this diagnosis as a subtype of ASD characterized by the absence of language delay and a normal or above-average IQ.[6]

This topic review will describe the essential aspects of autism spectrum disorder and Asperger syndrome. For greater transparency, the following have been referred to:

  • Asperger syndrome (AS): identified as a subgroup within the category of pervasive developmental disorders (PDD) as per the DSM-4-TR classification.
  • ASD: categorized as a range of neurodevelopmental conditions in the DSM-5.
  • Autism spectrum disorder of an Asperger syndrome type (ASD-AS): is a specific subgroup in the DSM-5 classification of ASD. ASD-AS is characterized by individuals who exhibit symptoms consistent with ASD, specifically at Level 1 severity, without accompanying intellectual impairment

Historical Perspective

In 1944, approximately one year after psychiatrist Leo Kanner first described infantile autism, Hans Asperger published a case report introducing a condition called "autistic psychopathy."In 1980, the American Psychiatric Association (APA) officially acknowledged autism as a distinct category in the DSM-3, where it was initially presented as "infantile autism." Following that, in 1981, psychiatrist Lorna Wing reignited research on Asperger's work and rebranded "autistic psychopathy" as "Asperger syndrome." A few years later, in 1989, the first diagnostic criteria for Asperger syndrome were proposed.

The 10th Revision of the International Classification of Diseases (ICD-10), introduced in 1993, was the first significant classification system to recognize Asperger syndrome (AS).[7] Then, in 1994, AS was formally introduced as a distinct entity in the DSM-4. It was categorized within PDD alongside autism spectrum disorder, marking an important milestone in recognizing and understanding AS as a separate diagnostic category. While during this period, researchers were focused on developing measures to diagnose AS and differentiate it from high-functioning autism (HFA), the DSM-5 removed the diagnostic category of AS in 2013.[5] The World Health Organization (WHO) also followed a similar approach in ICD-11, which came into effect in 2022.[2]

DSM Classification

The systematic description of psychiatric disorders is complicated, particularly in child and adolescent psychiatry. Asperger Syndrome was included in the DSM-5-TR in the large family of PDD. PDD has five subtypes:

  • Autism spectrum disorder
  • Asperger syndrome
  • Childhood disintegrative disorder
  • Pervasive developmental disorder not otherwise specified (PDD-NOS)
  • Rett syndrome

In DSM-IV-TR, the symptoms and clinical specifiers for autistic disorder within the pervasive developmental disorders (PDD) category fell into three broad categories: social interaction, communication, and restricted and repetitive behavior.[8] The diagnostic criteria for Asperger syndrome (AS) used to include:[7]

  • Individuals exhibiting at least two symptoms of social impairment and at least one symptom each from the category of communication deficits and restricted, repetitive behaviors (RRB).
  • Delayed or impaired functioning in at least one of the following areas: social interaction, language as used in social communication, or symbolic or imaginative play with onset before the age of three years.
  • Individuals who met the diagnostic criteria for autistic disorder (or another specific PDD) would not meet the criteria for AS. In such cases, the diagnosis of autistic disorder would take precedence.

AS, as contrasted with autistic disorder, was differentiated based on several key factors, as outlined:[9]

  • Absence of diagnostic criteria in the communication domain
  • Lack of a requirement for onset before age 3
  • Addition of criteria specifying the absence of a language delay
  • Addition of criteria specifying the absence of a deficit in cognitive development

This classification proposed a differential diagnosis between AS and high-functioning autism (HFA), a type of autistic disorder characterized by normal cognitive functioning. The differential diagnosis between AS and HFA sparked significant debate due to uncertainties in defining the specific criteria for AS and the clinical overlap between the two conditions. This debate is reflected in the literature, which has produced contradictory results regarding the distinctiveness of AS and HFA. While research has identified nuanced differences between the two disorders, most studies have emphasized the similarities between AS and HFA.

Ultimately, the DSM-5 removed PDD and its categorization and merged four subtypes into one category with a continuum named autistic spectrum disorders (ASD). This significant alteration was due to the assumption that PDD subgroups cannot be differentiated from one another certainly and reliably.[7] As a result, several changes were made in the classification system, including the following:[2][8]

  • Elimination of PDD and its subtypes.
  • Creation of a new diagnostic category called autistic spectrum disorders (ASD), encompassing autistic disorder, Asperger syndrome, childhood disintegrative disorder, and PDD-NOS.
  • Addition of three levels of severity for ASD. These severity levels help provide a more comprehensive understanding of the individual's functional impairments and support needs.
  • Shifting from the previous PDD classification, which consisted of 3 domains, to the ASD classification, which comprises 3 domains. These 2 domains encompass:
    1. Impaired social communication and interaction
    2. RRB, interests, and activities.
  • Addition of sensory symptoms in the RRB component of diagnostic criteria.
  • Changing the specification of the age of onset from age 3 to "early childhood."
  • Creation of a new diagnostic category called "social communication disorder" (SCD) to include individuals with difficulties in social communication and interaction but who do not meet RRB criteria found in ASD.
  • Removal of Rett syndrome from the classification based on recent genetic data.
  • Including social communication and interaction-related deficits in one criterion while excluding the deficit related to spoken language.

Controversy over the New Classification of ASD

The new classification has faced criticism in the literature, with some authors suggesting that it may lead to narrower criteria for ASD. As a result, there is concern that certain individuals, particularly those who are cognitively able or previously diagnosed with AS or PDD-NOS (pervasive developmental disorder not otherwise specified), may no longer meet the criteria for an ASD diagnosis. In summary, the main argument is that while the reduced sensitivity of the new ASD classification may increase specificity, it can have negative implications for service eligibility and the ability of researchers to integrate information and data from studies conducted under these criteria.[9][6] On the other hand, some authors argue that eliminating the specific diagnostic category for AS may lead to increased stigma toward individuals previously diagnosed with AS. This argument is based on the assumption that societies with a negative perception of autism as a significant disability may stigmatize individuals falling under the ASD umbrella. In contrast, AS has been associated with more positive stereotypes, and its removal as a separate category could potentially contribute to losing those positive associations.[2][10]

Thus, the new inclusion of AS in the category of ASD may have a negative effect on the identity of the individuals who have adopted this label as an identity. However, the literature on the potential impact of the DSM-5 changes on individuals previously diagnosed with AS is limited. The results of the discussions surrounding the changes in the ASD classification can be categorized into three groups: those who support the changes, those who oppose the changes, and those who express mixed feelings about the changes.[2]


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The understanding of the etiology of Asperger syndrome and autism has evolved. The outdated theory of "refrigerator mothers," which falsely attributed ASD to the emotional coldness of mothers, has been discarded. Similarly, family lifestyle, income, and educational level are no longer considered risk factors for the onset of ASD.[11] Our current understanding recognizes a complex interplay of genetic, neurological, and environmental factors in the development of ASD. Ongoing research continues to shed light on the multifaceted nature of ASD etiology.[12]

Genetic Factors

The role of genetics in the pathogenesis of AS and ASD is widely acknowledged and accepted.[4][11][13] Genome sequencing data suggests numerous genes are associated with ASD, although no specific mutation has been identified as unique to ASD.[14] It is estimated that between 400 to 1000 genes are likely to lead to a predisposition to autism.[15] These genes are involved in various biological functions related to brain development and function.[4][14] For example, individuals with AS and other endophenotypes related to autism are more likely to carry specific variations in a gene called GABRB3, previously linked to individual differences in empathy.[16] Another notable finding is the presence of copy number variants (CNVs) in approximately 9% of individuals with ASD in clinical samples. CNVs refer to DNA deletions or duplications that can disrupt gene function.[14]

There is a significant genetic overlap between ASD and other neurological, psychiatric, and neurodevelopmental conditions such as epilepsy, intellectual disability, and schizophrenia.[4][14] It is widely recognized that genetic factors associated with conditions like ASD can disrupt normal brain development by interfering with crucial biological pathways. These disruptions can impact various aspects of brain function, including neuronal connectivity, synaptic plasticity, and neurotransmitter signaling. Such disturbances can lead to atypical development and functioning of the brain, resulting in the manifestation of ASD symptoms.[17] Neuroimaging studies have shown abnormalities in different brain regions, such as the frontal cortex, hippocampus, cerebellum, and amygdaloid nucleus.[4] Also, brain overgrowth and accelerated head growth during infancy have been found in children with ASD.[18] Several pieces of evidence support the significant genetic contribution to the development of Autism Spectrum Disorder (ASD). These include:[19]

  • Higher incidence of autism in siblings compared with the general population[20]
  • The vital role of inheritance in twins with 98% concordance in monozygotic and 53% to 67% concordance in dizygotic twins
  • Heritability estimates range from 64% to 91%[14]
  • Unequal sex distribution (male predominance) 

Environmental Factors

The role of environmental factors in the etiology of ASD is an area of active ongoing research. Identifying modifiable risk factors associated with ASD is essential, particularly for reducing exposure of children and pregnant women to known neurotoxicants. Environmental factors may act as an independent risk factor or interact with existing genetic factors in individuals with a genetic predisposition to ASD. These environmental factors include various aspects such as parental age, perinatal and obstetric events, maternal factors, fetal environment, and exposure to toxins and teratogens.[14] Strong evidence shows that advanced paternal and maternal age is associated with a higher risk of having a child with ASD.[12] Perinatal factors such as preterm birth, low birth weight, intrapartum hypoxia, intrauterine exposure to valproic acid and thalidomide, and neonatal encephalopathy are also associated with increased risk for ASD. Other prenatal conditions associated with increased ASD risk include short interpregnancy intervals, multiple gestations, maternal obesity, gestational diabetes, and prenatal infections such as rubella and cytomegalovirus.[12][21]

Based on the systematic reviews of multiple extensive epidemiologic studies, it is crucial to note that there is no evidence to support an association between ASD and immunization as an environmental risk factor; thus, it is recommended that children with ASD should be vaccinated according to the routinely recommended schedule.[22]


The new classification of ASD in the DSM-5 presents challenges and limitations when monitoring ASD prevalence over time.[23] Various studies have indicated a trend of increasing prevalence rates, and this increase can be attributed to several factors. These factors include changes in the definition of ASD, improved and broader screening practices, and heightened awareness of ASD among healthcare professionals and the general population. While these factors contribute to the observed rise in prevalence, it is important to consider the possibility of an actual increase in the occurrence of ASD. The prevalence of ASD varies across different studies, primarily due to variations in the study population and the methodology used. Reported estimates of ASD prevalence have ranged from as low as 0.7 in 10,000 individuals to as high as 72.6 in 10,000 individuals.

According to the Centers for Disease Control and Prevention (CDC), the estimated prevalence of ASD ) in the United States is 11.3 in 1,000 individuals.[24] On a global scale, the prevalence of ASD is estimated to be approximately 7.6 in 1,000 individuals, or roughly 1 in 132 people worldwide.[25] The overall prevalence of AS is not completely clear, and it has been estimated at 2 to 7 in 1000 individuals.[1] ASD occurs more frequently in males than females, with a male-to-female ratio of approximately 4:1. However, a systematic review and meta-analysis conducted in 2017 suggested that the actual male-to-female ratio is closer to 3:1. This indicates that girls with ASD are at a higher risk of not receiving a clinical diagnosis compared to boys.[24]

Individuals with ASD have co-existing psychiatric and physical disorders, especially in young children. Over 70% of individuals with ASD experience additional conditions alongside their autism diagnosis. The presence of co-occurring conditions in individuals with ASD can significantly affect the functioning of the patient and the patient's family, as well as clinical management. Common co-occurring conditions associated with ASD include intellectual disability, attention deficit hyperactivity disorder (ADHD), tic disorders, anxiety, depression, and epilepsy. In contrast, ADHD, depression, bipolar disorders, anxiety, and tic disorders, are common co-occurring conditions associated with AS and HFA subpopulation of ASD.[23][26]

History and Physical

ASD is a heterogeneous, neurodevelopmental disorder encompassing a range of features and impairments. It is characterized by abnormal social communication and interaction; and restricted and repetitive behavior patterns. Symptoms in the early developmental period may not become fully evident until social demands exceed limited capacities. Specifiers in the diagnosis of ASD include the presence of intellectual disability, language impairment, medical or genetic condition, catatonia, and other neurodevelopmental, mental, or behavioral disorders. Each core symptom domain has 3 levels of severity, which are classified based on the severity of symptoms and the required level of support needed to assist with impairments. Separate ratings are necessary for each part (table 1).[15]

Individuals typically exhibit distinct clinical traits and presentations in the case of ASD-AS. AS is a subpopulation on the autism spectrum, presenting with core symptoms of ASD in the absence of intellectual disability or language delay. The clinical features are heterogeneous, varying according to age and psychiatric comorbidities.[27] While the early symptoms of ASD can be identified as early as 1 to 3 years, the diagnosis of AS is often delayed and commonly occurs around the age of 11 or even later.[27][28] The average age of diagnosis is around 5 years.

Illustrative Examples of Impaired Social Communication and Interaction[15]

1 - Deficits in social-emotional reciprocity:

  • Absent or limited interest in social interactions
  • Abnormal social approach
  • Failure of normal back-and-forth conversation
  • Reduced sharing of interests, emotions, or effects
  • Inability to start or appropriately respond to social interactions

2 - Deficits in nonverbal communicative behaviors used for social interaction

  • Poorly integrated verbal and nonverbal communication
  • Abnormal eye contact
  • Abnormal body language, facial expressions, and nonverbal communication
  • Abnormalities in understanding and use of gestures

3 - Deficits in developing, sustaining, and understanding relationships

  • Failure to adjust behavior to suit different social contexts
  • Absence of interest in peers
  • Difficulties in making friends

Illustrative Examples of Restricted and Repetitive Behavior, Interests, and Activities[15]

1 - Stereotyped and repetitive behaviors

  • Patterns of restricted and repetitive motor movements such as hand or finger flapping, toe walking
  • Patterns of restricted and repetitive use of objects
  • Patterns of restricted and repetitive speech

2 - Insistence on sameness and inflexible adherence to routines

  • Resistance to change routines such as eating particular foods, repetitive questioning about a specific topic
  • Ritualized patterns of verbal or nonverbal behavior

3 - Highly restricted interests that are unusual and abnormal in intensity or focus

4 - Atypical sensory behaviors, hyperreactivity or hyporeactivity to sensory input, unusual interest in sensory aspects of the environment

Specific symptoms of ASD are particularly relevant to specific age groups or certain subpopulations. For example, indicators such as a lack of orientation to name or failure to follow pointing gestures are reliable in identifying autism in toddlers and preschool children but may not hold the same significance in older children and adults. Similarly, the absence of close friendships is not developmentally concerning for a toddler but becomes more significant as individuals reach adulthood.[29]

Identifying the various clinical situations associated with ASD at different ages allows clinicians to provide appropriate screening, referral, diagnosis, and treatment. Practitioners commonly encounter various clinical settings at different ages of life in patients with ASD-AS, including the following:

Children and Adolescents

Social Isolation and Bullying at School[30]

Friendship is an essential social experience for children. It provides a context where they can develop the social skills required for friendship, including good social adaptability, understanding of emotions, empathy, and concern for others. Children with ASD-AS have difficulties with these social skills and therefore struggle to build friendships. However, research has shown that they are interested in having a relationship, ask themselves the reason for their loneliness, and identify the feeling of loneliness at an early stage.

Children with ASD-AS have difficulty interpreting details of nonverbal language, gestures, and facial expressions. They also do not fully understand humor and metaphors, have limited and sometimes unusual interests, and may speak with an unnatural intonation. Their unique challenges and limited social skills put them at a higher risk of experiencing interpersonal difficulties, making them vulnerable to being mocked by their peers. More than 40% of children with ASD have been victims of bullying and intimidation at school. It is not uncommon to see individuals with AS drop out of school due to developing significant anxiety and depressive symptoms as a result of their interpersonal difficulties.

Limited Fields of Interest, Awkwardness, and Clumsiness[31]

Some children with ASD-AS play repetitive and stereotypical games with no creativity. For example, they can play “pretending” for days. They exhibit an intense and focused preoccupation with limited interests that are often unusual or abnormal in their intensity. Children with ASD-AS often display a strong interest in specific objects or topics, such as technical train data, mechanics, space, history, music, or meteorology. They exhibit exceptional abilities in memorization. Motor coordination disorders and unusual gait and posture are common; thus, they have little interest in sports and experience difficulties performing activities such as drawing, writing, or fastening shirt buttons.

ADHD and Autism

Attention deficit hyperactivity disorder (ADHD), with or without hyperactivity, is the most common mental disorder among children and adolescents. Research has revealed overlapping symptoms between ADHD and ASD-AS, suggesting the need to consider ASD-AS when diagnosing ADHD in individuals experiencing significant interpersonal difficulties.[32] The high distractibility observed in ADHD and the reduced mental flexibility seen in ASD-AS can manifest as decreased attention levels. Furthermore, both conditions can contribute to difficulties in interpersonal relationships and exhibit a remarkable ability to engage intensely in their respective interests.

Heterogeneous Neurocognitive Profile

The neurocognitive profile of children with AS has been heterogeneous, although the verbal intelligence quotient (IQ) is generally higher than the performance IQ. Contrary to popular belief, not all individuals with Asperger syndrome are geniuses, and there is significant variability in cognitive abilities across different tasks. Individuals with ASD-AS often exhibit deficits in executive functions and tasks that require comprehensive treatment. However, they tend to excel in areas of fluid intelligence and problem-solving.

Sensory and Perceptual Characteristics

More than 90% of people with autism experience atypical sensory perceptions that could involve all senses and may lead to severe anxiety. Hypersensitivity is a common observation that may present with food selectivity or overreaction to a noisy environment, certain types of contacts, or body odor. Hyposensitivity symptoms such as lower pain thresholds, indifference to temperature, or circular movements could also be present.[6]


Delayed Diagnosis

It is not uncommon for ASD-AS to be diagnosed in adulthood. This delay in diagnosis is more likely because this subpopulation of ASD can fairly compensate for their social difficulties. Individuals with ASD-AS have average or superior intelligence, which can lead them to mask their deficits in social interaction and communication skills.[33] However, maintaining these compensatory strategies becomes increasingly challenging as the social environment becomes more complex. Additionally, their inflexibility of behavior and difficulties in coping with changes, such as entering into a romantic relationship or starting a professional career, eventually lead to a breakdown in their adaptive functioning. This can put them at risk for anxiety and depression. Warning signs in these individuals lack specificity and are mostly related to social interactions.

Potential for Misdiagnosis as Schizophrenia

Accurately distinguishing between schizophrenia and AS is not always easy. Misdiagnosing AS as schizophrenia can hinder effective therapy and lead to significant issues. Impaired social communication and interaction, limited interests, and delusions of persecution are clinical features that can be present in both conditions.[34] The apparent lack of affect, visual contact, and facial expressiveness in individuals with AS can be mistaken for the discordance of schizophrenia. Also, altering social interactions may be challenging to differentiate from the withdrawal period in schizophrenia subjects.

Moreover, impaired communication skills in AS can resemble the thought disorder observed in schizophrenia. However, certain clinical features are more indicative of AS, such as an earlier age of onset, repetitive behaviors, impaired pragmatic language, lack of imagination, peculiar intonation, and a strong inclination to engage in conversations about their favorite subject. It is also worth noting that individuals with ASD-AS may experience transient psychotic episodes characterized by depersonalization, derealization, and hallucinatory experiences.[6]

Decrease in Symptoms into Adulthood

Studies have indicated that ASD symptoms generally diminish as individuals with ASD transition into adulthood. This symptom reduction is more pronounced among those with average or above-average intelligence compared to individuals with ASD and intellectual disability. Social challenges, perceptual deficits, difficulties with nonverbal communication, and restricted and repetitive behaviors are reported to remain stable over time.[35]


Regarding sexuality, individuals with ASD-AS do not appear to differ significantly from the general population. People with autism have sexual and romantic desires and actively seek romantic relationships. However, they often struggle with the necessary social skills, and their behavior may be perceived as bizarre or disturbing. Failure to understand the appropriateness of behaviors in different social situations can result in individuals with ASD-AS engaging in behaviors that may be considered inappropriate in public settings. These behaviors can include unclothing, masturbating, engaging in awkward sexual conversations, or making improper attempts at seduction. These actions are not intended to be harmful or malicious but may be interpreted as harassment. Their repetitive and restricted behaviors and sensory fascinations may also disturb their sexual development; thereby, they may develop obsessions with sexual references, abnormal sexual fears, or compulsive masturbation with an object like fetishism.

Professional Scope

Due to the impaired pragmatic language skills in individuals with ASD-AS, they may communicate in a formal, direct manner without considering the social context or making efforts to avoid offending others. These challenges can be particularly evident in the workplace, especially in occupations that require teamwork and flexibility. Individuals with ASD-AS may struggle with cognitive inflexibility and adhere strictly to certain rituals or routines. Disruption of these rituals can lead to heightened anxiety and distress. For example, they may have specific preferences for placing items on their desk or rigid adherence to specific start and end times for their workday.

Obtaining their first job can be particularly challenging, despite having a university degree, due to the difficulties they may encounter during job interviews. Expressing their skills and behaviors in a way that aligns with social expectations can be perplexing for them. However, individuals with ASD-AS possess many valuable qualities, such as punctuality, honesty, creativity, and logical reasoning abilities.[6]


It is widely acknowledged that the core features of Asperger syndrome share similarities with other subpopulations within the ASD umbrella. Therefore, the ASD evaluation methods are broken up into screening and diagnostic assessment.

1. Screening

Screening tests are not used for diagnosis; they help identify individuals requiring further evaluation. Therefore, it is recommended to conduct general developmental screening at 9, 18, and 30 months to determine potential language, cognitive, and motor delays. However, these tests are not sensitive enough to capture differences in social interaction, playing, and repetitive behaviors associated with ASD. Thereby, it has been recommended to screen for ASD through a combination of the following:

A) Routine developmental surveillance at all visits: Developmental surveillance for ASD includes asking parents or caregivers about their concerns, observing caregiver-child interactions, and monitoring symptoms in every routine well-child visit.

B) Standardized autism-specific screening tests at 18 and 24 months of age: Screening tools are designed based on the early manifestations of ASD that providers or their caregivers can detect. Some of these early indicators are called "red flags," meaning they should alert providers to a higher risk for ASD.[14]

2. Screening Tools Used ASD Screening

  • Quantitative Checklist for Autism in Toddlers (Q-CHAT): one of the oldest methods to detect autism in children younger than 24 months.[36]
  • Modified Checklist for Autism in Toddlers (M-CHAT): A modified version of Q-CHAT and the most widely studied and used tool for screening toddlers for ASD. It is helpful for children younger than 30 months of age.[14]
  • Modified Checklist for Autism in Toddlers, Revised, with Follow-up (M-CHAT-R/F): A two-phase parent screening. This is a valuable method for research, educational and clinical purposes. It is helpful for children younger than 30 months of age.
  • Screening Tool for Autism in Toddlers and Young Children (STAT): A tool to screen children aged between 24 to 36 months. This is administered by a trained professional examiner who requires specific training to administer the assessment accurately. It can be used to support a preliminary diagnosis of ASD.
  • Autism Screening Instrument for Educational Planning, 3rd Version (ASIEP-3): A tool designed to identify children between 2 to 13 years and 11 months with a high level of autistic behavior. It is the most time-consuming screening tool, taking approximately 90 to 120 min to complete.
  • Autism Behavior Checklist (ABC): The ABC is a subtest of ASIEP-3.
  • Childhood Asperger Syndrome Test (CAST): A tool to screen children between 5 to 11 years suspected of having AS.[36]
  • Social Communication Questionnaire (SCQ): A tool to screen children older than 30 months.[14]
  • Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): A self-scoring ASD screening tool developed for adults.[36]

2. Diagnostic Assessment

Once the screening or developmental surveillance indicates a risk for diagnosis of ASD, a comprehensive diagnostic evaluation is indicated to determine the presence of ASD and the need for early intervention. 

2.1 Standard Psychiatric Assessment

A standard psychiatric assessment involves conducting thorough interviews with patients and caregivers to obtain a comprehensive understanding of an individual's psychiatric condition. This assessment aims to gather detailed information about the individual's history, including descriptions of behavior during formal testing, reports of behavior in various environments, past and current educational and behavioral interventions, family history, and relevant psychosocial issues. The history and examination should be conducted with careful consideration of diagnostic criteria according to DSM-5.[14][24]

2.2. Assessment Tools

Various tools for the assessment of ASD have been developed. Although none of these questionnaires alone is sufficient for diagnosis, they can provide a structured approach and support a knowledgeable clinician in applying diagnostic criteria of ASD.[14]

  • Autism Diagnostic Interview-Revised (ADI-R)
  • Autism Diagnostic Observation Schedule, Second Edition (ADOS-2)
  • Diagnostic Interview for Social and Communication Disorders (DISCO)[24]
  • The Asperger Syndrome Diagnostic Scale (ASDS)[5]

2.3. Evaluation of Co-occurring Developmental Conditions

Attention to other potential comorbid diagnoses is also an essential component of assessment. Co-occurring conditions may impact the symptomology of ASD in different ways and at different ages. Therefore, formal assessments of language, cognitive abilities, motor capabilities, sensory skills, and adaptive functions are integral to the diagnostic process.[24]

2.4. Medical Workup

  • Genetic testing: Practitioners should recommend and offer a genetic evaluation to all families as part of the etiologic assessment.[37] Potential benefits of establishing a genetic etiologic diagnosis include improved counseling provided to patients and families, preventing morbidity by treating medical conditions associated with the genotype, refining treatment options, and avoiding additional unnecessary tests.
  • Neuroimaging: MRI is not recommended for routine assessment, although it may be indicated in certain conditions such as atypical regression, micro- or macrocephaly, seizures, or abnormal neurologic examination.
  • Electroencephalogram (EEG): This is not recommended for routine assessment, although it may be indicated in some instances with seizures, atypical regression, or other neurologic symptoms.[14]

2.5. Physical Examination

A thorough and differential diagnosis-directed physical examination is essential to guide appropriate workup. This includes evaluation of growth, organomegaly, dysmorphic features, neurologic abnormalities, and skin manifestations of neurocutaneous disorders.[14]

Treatment / Management

Treatment strategies in individuals with AS/ASD may vary according to the patient's age, strengths, weaknesses, and needs. Treatment can also vary due to delivery modality and targeted areas of intervention. The goal of treatment includes minimizing core deficits, maximizing functional independence, and decreasing problematic behaviors that may restrict functional skills.[14] While various interventions are helpful for individuals with ASD, many do not have a solid evidence base, and none have emerged as superior.[24] Understanding intervention terminology helps clinicians appropriately and effectively communicate and advise families on therapy choices.(B2)

Behavioral Interventions

Behavioral interventions are started early in life through an intensive delivery, targeting the core symptoms through behavior modification and learning theory principles.[15] Most evidence-based intervention models are rooted in applied behavioral analysis (ABA) principles, which involve intensive behavioral interventions to enhance socially desirable behaviors and reduce undesirable behaviors that may impede an individual's progress. Behavior analysts design and supervise ABA interventions with different approaches based on goals, age, or the targeted skill.[14] An early intensive behavioral intervention (EIBI) program based on ABA is widely supported for young children. This highly individualized program utilizes various trials to teach and develop simple skills, gradually progressing to more complex skills. ABA techniques effectively improve social skills, academic tasks, communication abilities, adaptive living skills, and occupational skills.[24](B2)

Some argue that a dominant form of ABA therapy for ASD systematically violates the fundamental tenets of bioethics.[38]

Educational Interventions[39](A1)

Children with ASD need a structured educational plan involving strategic, intensive, and individualized interventions.[24] The Learning Experiences and Alternative Programs for Preschoolers and their Parents (LEAP) and the Treatment and Education of Autism and Related Communication Handicapped Children Program (TEACCH) are highly regarded and influential classroom-based models.[14] Although the curricula vary among programs, the goals are to enhance verbal and nonverbal communication and improve social, academic, and motor skills.[24](B2)

Speech and Language Interventions

Communication is an essential focused intervention in ASD management. Speech-language therapy is the most common intervention for children with ASD, which includes strategies such as reinforcement of speech sounds, exaggerated imitation, enhancing communicative acts, and imitation of the sounds. Augmentative and Alternative Communication (AAC) is introduced for children who do not speak spontaneously. AAC modalities include picture exchange communication systems, sign language, speech-generating devices, communication boards, and visual supports. Several methods are also available to enhance pragmatic language skills for individuals with fluent speech but impaired pragmatic language skills.[14][24](B2)

Developmental Interventions

Developmental interventions are designed based on developmental theory. Children learn social interaction, communication, and emotional regulation through interaction. Developmental interventions are focused on the relationship between the patient and the adult (parents or caregivers). These interventions teach adults to increase their level of responsiveness and engage in nondirective interactive strategies that can help the child develop social and communication skills in the context of playing activities.[14]

Pharmacologic Interventions

Presently, no medications are available explicitly targeting the core social and communication symptoms of ASD. However, the U.S. Food and Drug Administration (FDA) has approved two medications for treating specific associated symptoms of ASD. Risperidone and aripiprazole can be prescribed for short-term management of aggression, self-injury, irritability, and tantrums in children and adolescents with ASD.[15](B3)

Differential Diagnosis

Although relatively adequate language and cognitive development distinguish Asperger syndrome from other neurodevelopmental disorders, the social limitations associated with this condition are also found in the following:

  • Intellectual disability
  • Language disorders
  • Sensory impairments (hearing impairment)
  • Reactive attachment disorder
  • Obsessive-compulsive disorder
  • Anxiety disorders, including selective mutism
  • Childhood-onset schizophrenia
  • Rett syndrome
  • Social (pragmatic) communication disorder[24]
  • Attachment disorder[40]
  • Tic disorders (stereotypic movement disorder)[41]
  • Schizoid personality disorder

  • Schizotypal personality disorder

  • Semantic-pragmatic processing disorder


The outcome for patients with ASD-AS has shown to be variable in the literature, depending on the study sample size and population, inclusion criteria, case definition, and outcome measures. However, several factors appear to be related to prognosis, including IQ, language skills, and co-occurring psychiatric conditions.[42] A longitudinal study of patients with AS has found that approximately 23% of patients had a restricted outcome, 47% had a fair outcome, and 27% had a good outcome.[43]

Individuals with AS have a more favorable prognosis when they receive support from their families who possess knowledge about the disorder. These individuals can benefit from learning specific social guidelines; however, it is important to recognize that the underlying social impairment is expected to persist throughout their lives.


The presence of intellectual disability in individuals with AS and ASD is often associated with significant challenges in developing social competence. Additionally, when ASD is accompanied by language impairment, it further increases the risk of experiencing social difficulties. In other words, intelligence and language ability during childhood can serve as predictors of outcomes in adulthood. Approximately 9% of children diagnosed with ASD at an early age may no longer meet the diagnostic criteria for ASD in adulthood. Positive outcomes are more likely for those with higher cognitive skills and participation in early intervention services. Individuals who experience a significant increase in tested verbal IQ tend to show improved severity scores in adulthood. It is important to highlight that family and community support play a crucial role and have a greater impact on the reported quality of life for adults with ASD-AS or Asperger syndrome compared to the specific symptoms associated with the condition.[14]

Deterrence and Patient Education

Parents and families with children diagnosed with AS face numerous challenges, including feelings of frustration, social isolation, conflicts within relationships, and financial difficulties. They may experience heightened stress levels and are more prone to encountering negative consequences than parents of children with other disabilities.[44] Nevertheless, parental and family involvement plays a crucial role in managing AS. Specific interventions involve training parents and can be provided in the home setting.

Parent support interventions are knowledge-based training programs that indirectly impact the child by enhancing parental self-efficacy, providing care coordination, and offering psychoeducation. These interventions help parents gain skills and resources to support their children effectively. On the other hand, parent-mediated interventions focus on teaching specific techniques and involve trained parents or caregivers who directly apply these techniques to benefit the child. Parents or caregivers also play a vital role in teaching social skills, especially for young children. Emphasizing the importance of this responsibility is crucial for families. Additionally, educational interventions that include social skill instruction are essential for effectively managing individuals with autism spectrum disorder (ASD).[14]

Enhancing Healthcare Team Outcomes

All patients with Asperger syndrome should have a thorough medical assessment, including standard psychiatric assessment, physical examination, hearing screening, eye examination for signs of tuberous sclerosis, and genetic testing. Medical geneticists have recommended chromosomal microarray as the standard of care for the initial evaluation of children with ASD or other developmental disabilities.[24][45] [Level 1]

Additional evaluations may be warranted if the child presents with any atypical characteristics, such as a notable family history, dysmorphology, or a history of regression. Other potential organic etiologies such as infections, endocrinopathies, metabolic disorders, trauma, or fetal alcohol syndrome should also prompt further evaluation. Landau-Kleffner syndrome, a neurodevelopmental disorder associated with highly distinctive EEG abnormalities, should be considered. Neurologic consultation, neuroimaging, EEG, and additional laboratory tests may be indicated depending on history or physical examination.[24] [Level 1]

For diagnostic evaluation, most patients with Asperger syndrome need to see specialists such as a psychiatrist, psychologist, developmental-behavioral or neurodevelopmental pediatrician, or neurologist. Earlier clinical diagnosis is essential to facilitate the initiation of services. A detailed history of behavioral symptomology and direct observation of symptoms is necessary to make a diagnosis since no diagnostic laboratory tests are available.[14] [Level 1]

Psychological assessment is recommended for treatment planning as it assists in identifying the areas of strength and weakness in an individual. Various measures of cognitive ability and adaptive skills are employed to design effective intervention programs. It is important to note that intelligence tests may yield diverse and widely dispersed results, particularly in individuals with unique skills or special interests, especially those with higher functioning abilities. However, the intense focus on these specific interests may sometimes impede learning abilities. In addition to cognitive assessment, receptive and expressive vocabulary, and social and pragmatic language skills are evaluated to assess an individual's communication abilities. Occupational assessment may also be indicated to evaluate sensory and motor deficits that could impact daily functioning. Furthermore, a comprehensive evaluation should include an assessment of sleep patterns, as sleep disturbances can significantly impact overall well-being and functioning. Careful planning with interprofessional coordination helps optimize outcomes.[24] [Level 1]



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