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Developmental disorders are a group of conditions in which early brain
development is impaired. This very large group of disorders includes
diagnoses such as intellectual disability (ID) and autism spectrum
disorder (ASD). The core diagnostic features of ASD include
impairment in reciprocalsocial communication and social interaction,
and restricted, repetitive patterns of behavior, interests, or activities.
These symptoms must be present from early childhood and impair
everyday functioning. ASD is diagnosed clinically, though standardized
behavioral diagnostic instruments can assist this process. ASD is more
common in boys than girls, and the core diagnostic features can be
addressed through multiple different types of nonpharmacologic
interventions, including specialized education, physical therapy,
occupational therapy, speech and language therapy, and behavioral
therapy, such as applied behavior analysis (ABA).
Individuals with ID/ASD have high rates of comorbid ADHD.
Treatment of ADHD, especially hyperactivity, in individuals with
ID/ASD is similar to the treatment of ADHD in neurotypical individuals,
agonists, and atomoxetine. Compared to
their neurotypical peers though, individuals with ID/ASD and comorbid
ADHD experience lower effect sizes with ADHD treatment, lower
tolerated doses of ADHD medication, and more risk of adverse effects,
including increased rates of decreased appetite, insomnia, depressive
symptoms, irritability, and social withdrawal.
Some individuals with developmental disorders demonstrate symptoms of
irritability and aggression, which can sometimes be helped with a
pharmacologic intervention if nonpharmacologic interventions are
ineffective. The strongest evidence for the pharmacologic treatment of
irritability/aggression in individuals with developmental disorders exists
for the use of risperidone and aripiprazole to treat irritability in children
with ASD. Doses for this purpose are likely lower than those used to
treat schizophrenia or bipolar disorder, and adverse events are relatively
common and may include sedation, weight gain, and extrapyramidal
Individuals with developmental disorders are at high risk of having
comorbid anxiety and depression. Although no large prospective,
randomized, controlled trials (RCTs) exist to support the use of selective
serotonin reuptake inhibitors (SSRI) for this purpose, case studies and
open-labelstudies have shown possible benefits. RCTs of SSRIs for the
treatment of repetitive behavior in children with developmental disorders
have shown mixed results, although they have demonstrated that
individuals with developmental disorders may be at increased risk of
emotional and behavioral adverse events from SSRIs, and therefore,
target dosing should be lower than in individuals with typical
Individuals with developmental disorders have high rates of comorbid
medical and psychiatric disorders, and therefore may often be
prescribed multiple different concurrent medications. Precaution should
be taken to avoid any pharmacodynamic or pharmacokinetic drug–drug
interactions, and such interactions should always be considered to
Sleep disturbances are common in individuals with developmental
disorders. Melatonin has the strongest body of evidence for being a safe
and effective treatment of sleep disturbances in this population.
Developmental disorders are a group of conditions characterized by impaired early
brain development, resulting in deficits of cognitive, communicative, behavioral,
sensory, or motor functioning. This broad group of disorders includes diagnoses such
as intellectual disability, and autism spectrum disorder (ASD), which will be the
focus of this chapter, attention-deficit/hyperactivity disorder (ADHD) and tic
disorder, which are covered in another chapter, and communication disorders,
learning disorders, cerebral palsy, congenital hearing loss, and congenital blindness.
Intellectual disability (ID), previously labeled mental retardation, is a disorder with
deficits in intellectual and adaptive functioning. Although ID is typically reserved for
older children, for whom intellectual testing is more valid and reliable, global
developmental delay (GDD) is the diagnosis given to younger children in which
delays exist in two or more developmental domains. ASD, which includes prior
diagnoses of autistic disorder, Asperger disorder, and pervasive developmental
disorder (PDD) not otherwise specified, is a condition involving deficits in social
communication, as well as the presence of restricted and repetitive patterns of
behavior, interests, or activities.
EPIDEMIOLOGY, NATURAL COURSE OF THE
Developmental disorders are common in the community, affecting as many as 15% of
children in the U.S., based on parent report.
2 Collectively, developmental disorders
are nearly twice as likely in boys and children insured by Medicaid, relative to girls
and those insured by private insurance, respectively.
prevalence of developmental disorders is reported by families with incomes below
the federal poverty level and with lower maternal education (any educational
attainment less than a college degree).
For ID and GDD, the overall prevalence is estimated to be between 1% and 3% of
the population, though with considerable variability depending on how the diagnosis
is defined and reported in the literature.
Intellectual disability is more prevalent in
males versus females, and in low- and middle-income countries relative to highincome countries.
ASD is increasing in prevalence, with the Centers for Disease Control and
Prevention reporting about 1 in 68 children (1.47%) being identified with the
5 Although around one-third of children with ASD may also qualify for
intellectual disability, the proportion of children with average or above average
intelligence being diagnosed with ASD has been steadily increasing over the years
and may explain some of the increase in overall ASD prevalence.
children with ASD who are boys has consistently been 4 to 5 times that of girls.
the United States, around 30% of children with ASD have some level of ID.
The course and prognosis of both ID and ASD vary considerably depending on the
severity of the deficits, the impact of comorbid medical and psychiatric conditions,
and the access to services and treatments. Many individuals will go on to live rich
and fulfilling lives, with minimal required assistance in daily life functioning, though
some will require constant supervision in supportive group housing, and assistance
for basic tasks of daily living.
PATHOPHYSIOLOGY: DISEASE ETIOLOGY,
Many different known and unknown genetic and environmental factors can lead to the
impairment in early brain development associated with developmental disorders.
For both ID and ASD, risk factors include preterm birth, low birth weight, small
for gestational age, and low Apgar scores, though all of these are associated more
6 For ID specifically, risk factors may differ depending on the
severity of ID. Studies have shown risk factors for mild ID to include mothers under
the age of 20 years or older than 30 years, paternal age greater than 40 years,
increasing birth order, increasing social disadvantage, maternal education less than
high school, being part of a multiple birth, and being second or later in the birth
7,8 The risk of severe ID was consistently increased with increasing maternal
age and decreasing level of maternal education.
7 For ASD without ID, additional risk
factors include mothers aged 35 years or older, first-born infants, male infants, and
increasing socioeconomic advantage.
In only about half of all cases of ID can a specific etiology be identified and may
include genetic anomalies, intrapartum asphyxia, cerebral dysgenesis, and
In only about 30% of children with ASD can an identifiable
genetic etiology be determined.
10 Although inherited genetic forms of ID likely
represent a minority of identified cases, ASD on the other hand is widely considered
to be one of the most heritable neuropsychiatric conditions with heritability estimates
11 For parents with one child with ASD, the recurrence rate in future
siblings is thought to be 5% to 20%, with higher rates if the original child with ASD
12 This recurrence rate increases to about 33% if a family already has two
For inherited genetic anomalies, X-linked gene defects account for 10% to 12% of
all ID cases in males, with fragile X syndrome being the most common.
syndrome, marked by a CGG triplet repeat expansion in the FMR1 gene on the X
chromosome, is also the most common single-gene cause of ID, accounting for about
0.5% to 3% of individuals with ID,
14 and ASD, accounting for around 1% to 3% of
10,15 Single-gene disorders, some heritable like fragile X syndrome, account for
about 5% to 7% of ASD cases and include PTEN macrocephaly syndrome (~1%),
tuberous sclerosis complex (~1%), and Rett syndrome (~1%).
causes of ID and ASD include inherited metabolic disorders, such as
phenylketonuria, adenylosuccinate lyase deficiency, and Smith–Lemli–Opitz
15 Although inherited metabolic disorders are relatively rare, accounting
for only 1% to 5% of cases of ID, the potential for positive prognosis with treatment
Other genetic anomalies that can lead to ID and ASD include noninherited, or de
novo, single-gene mutations, chromosomal aberrations, and imprinting/epigenetic
14 Chromosomal aberrations may account for up to 25% of individuals with
ID, about 8% or 9% of which is due to trisomy 21, or Down syndrome, the most
14,16 Prader–Willi and Angelman syndromes, both
associated with developmental delays, are two examples of disorders involving
Environmental causes of ID range in the literature from 2% to 13% and include
antenatal toxin exposure (e.g., fetal alcohol spectrum disorders), antenatal infection
(e.g., TORCH infections), and early severe psychosocial deprivation.
Environmental causes of ASD include first trimester intrauterine exposure to
valproic acid, thalidomide, misoprostol, the organophosphate insecticide
chlorpyrifos, and phthalates, in addition to first trimester rubella infection.
receiving much scrutiny, multiple studies have shown no support linking vaccines to
Developmental disorders are typically recognized clinically once it becomes clear
that a child is delayed in meeting one or more developmental milestones. Primary
tasked by the American Academy of Pediatrics (AAP) to assess development at
every routine preventative visit throughout childhood.
encourages pediatricians to use standardized developmental screening tools (e.g.,
Ages and Stages Questionnaires—ASQ and Parents’ Evaluation of Developmental
Status—PEDS) at the 9-, 18-, and 24- or 30-month visit, and an autism-specific
screening tool at the 18- and 24-month visits (e.g., Modified Checklist for Autism in
21,22 Once concerns are raised by routine surveillance or
screening measures, children should be referred to early intervention and early
childhood programs, as well as to developmental specialists, when indicated.
Early recognition of developmental disorders depends on children having access
to preventative medical care, and almost 25% of children with special health care
needs might not have that access.
23 The nature and severity of the developmental
deficits also contribute to the age at recognition. The sensitivity of developmental
and autism screening measures rarely reaches 0.9,
developmental deficits may go undetected. For children with ASD, the mean age of
diagnosis has been around 53 months,
though children with intellectual disability
and those diagnosed with autistic disorder are typically diagnosed earlier; children
with higher IQ scores and those eventually diagnosed with Asperger disorder, whose
limitations do not include communication delays, are typically diagnosed later.
Some individuals with particularly subtle deficits may not be diagnosed until
adulthood. Individual symptoms that may lead to an earlier diagnosis of ASD may
include severe language deficits, hand flapping, toe walking, and sustained odd
ID is defined by both the American Psychiatric Association and the American
Association on Intellectual and Developmental Disability (AAIDD) as a disorder
with deficits in intellectual and adaptive functioning in conceptual, social, and
1,25 The Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-V) requires that the disability has onset “during the
developmental period,” whereas the AAIDD requires the disability to start before
age 18 years. Intellectual functioning is assessed clinically and by standardized tests
of intelligence, like IQ testing (e.g., Wechsler Intelligence Scale for Children and the
Stanford–Binet Intelligence Scale), with a cutoff being two standard deviations
below the mean for the general population, or a score of around 65 to 75, for
1 Older references focused diagnosis primarily around IQ scores, and
subcategories of intellectual disability (then called mental retardation) were set to
1 Current methods of diagnosis focus more on measures of
adaptive functioning, because this is more relevant to planning treatment and
supports. Adaptive functioning is also assessed clinically or with standardized tests
of adaptive functioning (e.g., Vineland Adaptive Behavior Scales). Subcategories for
intellectual disability in the DSM-V are now based on levels of adaptive functioning,
mild, moderate, severe, and profound. As standardized testing for intellectual and
adaptive functioning is typically valid for children above the age of 5 years, for
children younger than 5 years, the diagnosis of GDD is used and describes significant
delays in two or more developmental domains, including gross/fine motor,
speech/language, cognition, social/personal, and activities of daily living.
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