Pervasive Developmental Disorder

Updated: Oct 19, 2018
  • Author: Sufen Chiu, MD, PhD; Chief Editor: Caroly Pataki, MD  more...
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Practice Essentials

Historically, pervasive developmental disorder (PDD) described a group of several disparate disorders unified under the main principle of delayed language development and deficits in social interaction. As molecular genetics and cognitive neuroscience developed, furthering the understanding of these disorders, new criteria now grouped them under autism spectrum disorder (ASD), emphasizing deficits in social interaction. This group of disorders will be referred to as ASD throughout the article.

In an effort to increase diagnostic sensitivity and specificity for disorders on the autism spectrum, various revisions to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were made in 2013. These revisions have generated new diagnostic criteria for ASD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). [1, 2]  Specifiers are used to designate conditions associated with known medical or genetic conditions. Conditions with social communication deficits without clear social interaction issues are now grouped under communication disorders.

The new criteria have raised concerns that a redefinition of the diagnosis of autism may exclude some children and render them ineligible for services. In a study from New York, the new DSM-5 criteria for ASD were found to identify 91% of children previously diagnosed with pervasive developmental disorder (PDD) on the basis of DSM-IV criteria. Many of the remaining 9% would probably have the diagnosis reinstated on the basis of clinician input. [3, 4]  Even when the researchers examined different PDD subgroups, they found that the new criteria had a high sensitivity for identifying girls with ASD, as well as those in the high-functioning range of cognitive ability and those with a nonverbal IQ of 70 or less. Previous DSM-IV criteria often overidentified children with intellectual disability (IQ of 70 or less) and missed girls or those who were high functioning.

Several additional retrospective studies assessed the impact of DSM-5 changes on diagnostic rates and reported considerably lower sensitivities. These studies demonstrated regional variation in application of  DSM-IV criteria. With the improved specificity of DSM-5 criteria, including the introduction of the new diagnosis "social (pragmatic) communication disorder," more consistent prevalence rates of communication disorders, distinct from ASDs, were determined. Further molecular genetic and cognitive neuroscience research will likely continue to shape the ASD criteria over time.



Under DSM-IV, pervasive developmental disorder included four separate disorders: autistic disorder, Asperger’s disorder, childhood disintegrative dsorder, and Rett syndrome in addition to the catch-all diagnosis of pervasive developmental disorder not otherwise specified (PDD-NOS). Molecular genetic research indentified a single defect as the basis of Rett's disorder, which then clarified that not all individuals with Rett syndrome have social deficits. The new diagnostic category of autism spectrum disorders (ASD) in DSM-5 sought to improve specificty of diagnosis by clarifying that ASD is not a degenerative disorder, thereby eliminating childhood disintegrative disorder. Most individuals diagnosed with a pervasive developmental disorder (PDD) from DSM-IV should still meet the criteria for ASD in DSM-5 or another, more accurate DSM-5 diagnosis. [2]

ASD in its most severe presentation may describe a preschool-aged child who presents with no expressive language, seeks comfort from parents in atypical ways, engages in repetitive hand flapping, and makes no eye contact. In the mildest presentation, the disorder may include a child aged 9 years with poor peer interactions, normal verbal abilities, and mild nonverbal disabilities. The mild nonverbal disabilities make it difficult for the child to follow subtle social cues and affective signals that most children easily interpret as anxiety, anger, or sadness. The child's preoccupation with a restricted interest and attention to detail often tries the patience of peers with similar interests who are developing normally. (See History, Etiology.)

Symptoms of PDD or ASD that may begin during the first year of life include lack of joint attention. A normally developing 1-year-old infant would make eye contact with a parent, point at an object for the parent to see, and smile responsively if the parent identifies the object. A child at risk for PDD or ASD often lacks these behaviors. While some toddlers may be identified through pediatric screening using instruments such as the M-CHAT, [5]  many children may escape clinical attention until adolescence. Adolescents with normal development begin to use abstract thinking, realize that people have differing opinions, and learn to accept them. Adolescents with PDD or ASD often present with rigid thinking, are unable to accept other's opinions, and explode behaviorally when they cannot convince others to adhere only to their opinion.

Genetic and cognitive neuroscience research is starting to provide a framework for understanding the biology of social interactions. Identification of social deficits is now possible even before one year of age. Early identification and treatment leads to better outcomes. For these reasons, mandated insurance coverage of  treatment for autism spectrum disorder is now available in California. Delayed treatment leads to greater impairment and utilization of future resources.

Go to Autism, Asperger Syndrome, and PET Scanning in Autism Spectrum Disorders for additional information on these topics.

Associated morbidities

Identified organic disorders that occur with PDD/ASD include epilepsy (the most common medical condition associated), cerebral palsy, fragile X syndrome, fragile X premutation involvement, tuberous sclerosis, phenylketonuria, neurofibromatosis, Down syndrome, and congenital rubella. Roughly 30% of patients with PDD/ASD present with a known medical disorder. [6] Seizures are the most frequent comorbidity. Deletions or duplications (eg, 15q duplication) are the most common genetic abnormality associated with PDD/ASD. [7] (See Etiology.)

ASD is commonly comorbid with intellectual disability. Fragile X syndrome is the most common genetic cause of intellectual disability. Therefore, autistic disorder should be common in those with fragile X syndrome. Several studies have demonstrated an excess of autistic symptom clusters and clinical findings, such as larger head circumference, in individuals with fragile X syndrome greater than would be expected among persons with intellectual disability without a genetic etiology. [8] These features are absent in cases of fragile X syndrome without autism. Therefore, a subtype of fragile X syndrome may be an ASD behavioral phenotype. As evidence mounts that ASDs have biological origins, these genetic syndromes may be used as models to develop new treatment strategies for them. (See Etiology.)

Symptoms of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) are often present in patients with ASD. Some clinicians label the OCD and ADHD symptoms separately, whereas others include them as part of the presentation of ASD. Regardless of the approach, the symptoms of OCD and ADHD may be disabling and require treatment with standard approaches that include, but are not limited to, medications and behavioral therapy.

Aggression is a symptom not specific to any particular psychiatric disorder but may be particularly troubling in ASD because the children cannot always communicate the cause of their distress. The etiologies are broad and include constipation, anxiety, depression, anxiety, psychosis, or adjustment disorder. Treatment requires clarification of etiology to help select medications and other appropriate therapies. [9, 10]

A study using subjects recruited from the Autism Speaks Autism Treatment Network consortium identified depression in 7% of individuals with ASD based on parent report. Age, IQ, history of seizures, and gastric complications increase the likelihood of depression. [11] Therefore, the prevalence of depression is likely to be higher because many children with ASD are unable to provide the subjective self-report that is traditionally needed for the identification and diagnosis of depression.

The evaluation of anxiety disorders in ASD is problematic as well given that symptoms often require subjective self-report. Evidence-based guidelines have been developed by a multidisciplinary work group of clinicians and researchers through the Autism Speaks Autism Treatment Network. [12] These assessments take extended time and sensitivity. For example, an assessment of the child's ability to understand and express emotion would first involve questions like, "Do you know what worried means?" Modified cognitive-behavioral therapy (CBT) has been shown to be beneficial for children with ASD in preliminary studies.

Sleep problems are extremely common in ASD. A study using the Children's Sleep Habits Questionnaire identified 715 of children with clinically significant sleep problems. [13] The number of children meeting criteria for a sleep disorder was 30%. Medications prescribed to 46% of 4- to 10-year-olds with a sleep disorder diagnosis.

Sensory integrations disorder is not found in the DSM-IV, DSM-5 or the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) but best captures the behavioral problems that result when individuals with ASD become disruptive when bothered by loud noises, tags on clothing, or textures of food. They may also be disruptive while trying to seek alternative methods of self-soothing, such as swinging, wrapping themselves in heavy blankets, or eating nonnutritive items. Identification of these sensory needs or deficits is integral to the behavioral management of individuals with ASD. Emerging controlled studies support the efficacy of these interventions in improving behavior in ASD.

Milestone regression

Regression, or the loss of developmental milestones, was once a controversial finding in autistic disorder. Today, differing degrees of regression are recognized as part of the developmental presentation of ASD. [14]  However, major losses of multiple developmental milestones suggest Rett syndrome or other genetic or metabolic disorders. Certain mitochondrial disorders occur only in the brain and therefore may present without any motor or peripheral deficits. Landau-Kleffner syndrome (LKS) is an epileptic disorder that typically has a fluctuating course. In LKS, regression in language development occurs repeatedly due to seizure activity. Childhood disintegrative disorder is no longer in the DSM-5 because of the difficulty in clarifying diagnostic criteria. Many cases diagnosed in the past were likely due to genetic causes that now are readily diagnosed with improvements in technology.

Also see Acquired Epileptic Aphasia.



Researchers continue to identify multiple etiologies for the underlying pathophysiology of pervasive developmental disorder (PDD/ASD). Different levels of dysfunction in CNS systems are most likely involved. For example, at the molecular level, the type of serotonin-transporter gene promoter may modulate the severity of ASD or increase the risk for its development. [15] Data from a blood genomic study have suggested that the immune system plays a role. [16] At the neuroanatomic level, preliminary brain imaging studies have shown differences that may manifest clinically as a larger head size. [17]  Environmental factors such as paternal age may also contribute to development of ASD, although mercury exposure and vaccinations have mostly been dismissed.

Changes in culture may explain some of the increased rates of ASD. A study correlated increased time spent indoors with increased rates of ASD and suggested that this was caused by increased television viewing. [18] Television may reinforce repetitive behaviors in vulnerable children who, in a different era, would not have spent so much time with computer games and television programming. Screen time may also take away from opportunities for interpersonal interactions and social skill development.

Children with ASD may have other specific cognitive deficits, including central auditory processing problems, which imply distorted pathways between hearing and cortical processing. They may also have specific cognitive strengths. In isolated cases, these special cognitive talents lead to these individuals being labeled savants.

Some of these deficits and strengths may manifest as sensory integration issues. For example, children with ASD may have hyperacoustic hearing, predisposing them to act erratically around loud noises. The hyperacoustic hearing may enable some children with ASD to be gifted musicians. [19] Temple Grandin, a distinguished author and professor with Asperger disorder, writes about her need for increased tactile stimulation, which helped her develop a more humane way to move cattle. [20]

Children with fragile X syndrome have many of these cognitive deficits. The genetic and molecular basis of fragile X syndrome has been described in detail, supporting the premise that deficits in the protein encoded by the fragile X syndrome gene result in glutamate disturbance and abnormal neuronal axonal development. [21] The protein FMRP, encoded by the fragile X syndrome gene, may interact with other neurotransmitters or processes to cause autistic symptoms in fragile X syndrome more often than in other genetic syndromes or nonsyndromic intellectual disability.

Since the identification of the genetic abnormality in Rett syndrome, milder cases of Rett syndrome with smaller deletions have been identified. [22] Individuals with milder cases of Rett syndrome have better intellectual ability and more classic symptoms of ASD. The genetic defect in Rett syndrome results in alterations in the power center equivalents of brain cells, also known as mitochondria. [23]



Incidence in the United States

A survey of existing literature by Fombonne in 2003 indicated that the rate for all forms of pervasive developmental disorder (PDD/ASD) was 30-60 cases per 10,000 population, while the rate for Asperger disorder was 2.5 cases for 10,000 population and the rate for childhood disintegrative disorder was 0.2 case per 10,000 population. Fombonne attributed an increase in prevalences over time to changes in case definitions and to improved awareness. [24]

An epidemiologic survey confirmed the prevalence of ASD to be 1 in 150 children. [25]  The increase in reported cases of ASD probably results from an increased identification of cases that do not meet specific criteria for autistic disorder or Asperger disorder but are diagnosed as PDD not otherwise specified (PDD-NOS) under DSM-IV. The DSM-5 reports the prevalence as 1%. [2]

The Centers for Disease Control and Prevention reported the prevalence of ASD to be one in 59 children aged 8 years from 11 sites of the Autism and Developmental Disabilities Monitoring (ADDM) Network. Only 86% of the children met both DSM-IV-TR and DSM-5 criteria. They also reported that the prevalence varied among racial/ethnic groups and communities. The main limitation of this study is that the sites were not selected to represent the United States as a whole. [26]

International incidence

No evidence suggests that the international prevalence of ASD differs from the prevalence in the United States. However, the literature indicates that these disorders are identified at a later age in specific regions of the United States than in other countries. [27]

Race predilection

Race has not been implicated as a risk factor for ASD.

Sex predilection

Sex bias for ASD is significant. ASD may be 5 times more common in boys than in girls. Asperger syndrome as defined in the DSM-IV may be 10 times more common in boys than in girls.

Only Rett syndrome affects more girls than boys; in fact, Rett syndrome is rarely diagnosed in boys. However, new molecular testing for Rett syndrome indicates that the incidence of the condition is greater in boys than previously reported.

Age predilection

Previously, autistic disorder carried an onset criterion; evidence of the disorder must be present by age 3 years. DSM-5 allows for a wider range of age onset, specifying only that symptoms begin in the early developmental period. Symptoms may have onset later if more subtle or may be masked in adults who developed compensatory behaviors. Regression in domains other than social communication after age 2 years usually warrants further evaluation for Rett syndrome and other genetic disorders. 

As noted earlier, ASDs are diagnosed relatively late in United States compared with other countries. [27] Within the United States, geographical differences in age of diagnosis present a significant public health challenge as evidence mounts to support early diagnosis and intervention.


Patient Education

Many parents of children with ASD need legal guidance to help them understand their legal rights to benefits and services available from public schools and from the medical system. Educational advocates are often necessary. Alternative treatments may drain the financial resources of families and potentially cause harm to the child. [28]

One study showed that parents with private insurance have a much higher financial burden for medical care than those with combined public (Medicaid) and private insurance. [29] Parents should be informed that they may qualify for Medicaid through the Family Opportunity Act of 2005, eligibility rules that exclude parental income. Interestingly, parents preferred Medicaid alone to combined coverage even though they had the greatest financial burden. Having combined insurance may lead to more difficulties in navigating health care systems.

For patient education information, see the Brain and Nervous System Center, as well as Autism and Asperger Syndrome.



A unified pathophysiology understanding of autism spectrum disorders will include a complex model of genetic, molecular, and system changes. For example, genes like SHANK, which are postsynaptic scaffolding proteins, alter synapse formation and maintence. [30] Scaffolding proteins interact with cell adhesion molecules (CAMs). Mouse models with altered CAM functioning have social deficits. These molecular changes then lead to altered inhibitory GABAergic synaptic transmission in the somatosensory cortex. Downstream effects on excitatory transmission and long-term potentiation may result. The mTor Pathway is important in growth regulation and protein synthesis, which affects neuronal plasticity. Changes in these systems ultimately result in neuroanatomical and cognitive deficits found in ASD. Environmental influences from toxins to learning will modulate and ultimately determine the severity of the symptoms associated with ASD.



Absence of intellectual disability and languague disability are the best prognostic factors for pervasive developmental disorders (PDD/ASD). [2] Functional language by age 5 is associated with better outcomes. In contrast, epilepsy associated with intellectual disability predicts poorer outcomes. Adaptive skills are usually below expected for intellectual ability which then impacts education and independence as adults.