1122
Chapter 31: Child Psychiatry
behaviors (e.g., head-banging and self-biting), and repetitive
stereotypical behaviors (hand-flapping and toe-walking). In
children and adults with milder forms of intellectual disability,
negative self-image, low self-esteem, poor frustration tolerance,
interpersonal dependence, and a rigid problem-solving style are
frequent.
Neurological Disorders
Seizure disorders occur more frequently in individuals with
intellectual disability than in the general population, and preva-
lence rates for seizures increase proportionally to severity level
of intellectual disability. A review of psychiatric disorders in
children and adolescents with intellectual disability and epi-
lepsy, found that approximately one third had comorbid autism
spectrum disorder. The combination of intellectual disability,
epilepsy, and autism spectrum disorder has been estimated to
occur in 0.07 percent of the general population.
Psychosocial Features
A negative self-image and poor self-esteem are common fea-
tures of mildly and moderately intellectually disabled persons
who are aware of their social and academic differences from
others. Given their experience of repeated failure and disap-
pointment in being unable to meet their parents’ and society’s
expectations, they may also be faced with falling progres-
sively behind younger siblings. Communication difficulties
further increase their vulnerability to feelings of ineptness
and frustration. Inappropriate behaviors, such as withdrawal,
are common. The perpetual sense of isolation and inadequacy
has been linked to feelings of anxiety, anger, dysphoria, and
depression.
Etiology
Etiological factors in intellectual disability can be genetic, devel-
opmental, environmental, or a combination. Genetic causes
include chromosomal and inherited conditions; developmental
and environmental factors include prenatal exposure to infec-
tions and toxins; and environmental or acquired factors include
prenatal trauma (e.g., prematurity) and sociocultural factors.
The severity of intellectual disability may be related to the tim-
ing and duration of a given trauma as well as to the degree of
exposure to the central nervous system (CNS). In about three
fourths of persons diagnosed with severe intellectual disability,
the etiology is known, whereas the etiology is apparent in up to
half of those diagnosed with mild intellectual disability. A study
of 100 consecutive children diagnosed with intellectual disabil-
ity admitted to a clinical genetics unit of a university pediatric
hospital reported that in 41 percent of cases, a causative diag-
nosis was made. No cause is known for three fourths of persons
with IQ ranging from 70 to 80 and variable adaptive function-
ing. Among chromosomal disorders, Down syndrome and frag-
ile X syndrome are the most common disorders that usually
produce at least moderate intellectual disability. A prototype
of a metabolic disorder associated with intellectual disability
is phenylketonuria (PKU). Deprivation of nutrition, nurturance,
and social stimulation can potentially contribute to the develop-
ment of at least mild forms of intellectual disability. Current
knowledge suggests that genetic, environmental, biological, and
psychosocial factors work additively in the emergence of intel-
lectual disability.
Genetic Etiological Factors in
Intellectual Disability
Single-Gene Causes.
One of the most well-known sin-
gle gene causes of intellectually disability is found in the
FMR1
gene whose mutations cause fragile X syndrome. It
is the most common and first X-linked gene to be identified
as a direct cause of intellectual disability. Abnormalities
in autosomal chromosomes are frequently associated with
intellectual disability, whereas aberrations in sex chromo-
somes can result in characteristic physical syndromes that
do not include intellectual disability (e.g., Turner’s syndrome
with XO and Klinefelter’s syndrome with XXY, XXXY, and
XXYY variations). Some children with Turner’s syndrome
have normal to superior intelligence. Agreement exists on
a few predisposing factors for chromosomal disorders—
among them, advanced maternal age, increased age of the
father, and X-ray radiation.
Visible and Submicroscopic Chromosomal Causes of
Intellectual Disability.
Trisomy 21 (Down syndrome) is a pro-
totype of a cytogenetically visible abnormality that accounts
for about two-thirds of the 15 percent of intellectual disabil-
ity attributable to visible abnormal cytogenetics. Other micro-
scopically visible chromosomal abnormalities associated with
intellectual disability include deletions, translocations, and
supernumerary marker chromosomes. Typically, microscopic
chromosome analysis is able to identify abnormalities of 5 to
10 million base pairs or greater.
Submicroscopic identification requires the use of microar-
rays that can identify losses of chromosomal segments too small
to be picked up by light microscopy. The altered copy number
variants (CNVs) in submicroscopic segments of the chromo-
some have been identified to be associated with up to 13 to
20 percent of cases of intellectual disability. That is, the genes
associated with a particular developmental abnormality have
been identified to be located in the critical regions of the patho-
genic copy number variants.
Genetic Intellectual Disability and
Behavioral Phenotype
Specific and predictable behaviors have been found to be asso-
ciated with certain genetically based cases of intellectual dis-
ability. These behavioral phenotypes are defined as a syndrome
of observable behaviors that occur with a significantly greater
probability than expected among those individuals with a spe-
cific genetic abnormality.
Examples of behavioral phenotypes occur in genetically
determined syndromes such as fragile X syndrome, Prader-
Willi syndrome, and Down syndrome in which specific behav-
ioral manifestations can be expected. Persons with fragile X
syndrome have extremely high rates (up to three fourths of
those studied) of ADHD. High rates of aberrant interpersonal
behavior and language function often meet the criteria for autis-
tic disorder and avoidant personality disorder. Prader-Willi
