31.3 Intellectual Disability
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syndrome is almost always associated with compulsive eating
disturbances, hyperphagia, and obesity. Socialization is an area
of weakness, especially in coping skills. Externalizing behavior
problems—such as temper tantrums, irritability, and arguing—
seem to be heightened in adolescence.
Down Syndrome.
The etiology of Down syndrome,
known to be caused by an extra copy of the entire chromosome
21, makes it one of the more complex disorders. The original
description of Down syndrome, first made by the English phy-
sician Langdon Down in 1866, was based on physical charac-
teristics associated with subnormal mental functioning. Since
then, Down syndrome has been the most investigated, and
most discussed, syndrome in intellectual disability. Recent data
have suggested that Down syndrome may be more amenable
to postnatal interventions to address the cognitive deficits that
it produces than was previously thought. Although still in the
early stages of animal research, data from experiments with one
mouse model, the Ts65Dn, indicates that pharmacologic inter-
ventions may influence learning and memory deficits known to
occur in Down syndrome.
Phenotypically, children with Down syndrome are observed
to have characteristic physical attributes, including slanted eyes,
epicanthal folds, and a flat nose.
The etiology of Down syndrome is complicated by the recognition
of three types of chromosomal aberrations in Down syndrome:
1. Patients with trisomy 21 (three chromosomes 21, instead of
the usual two) represent the overwhelming majority; they have
47 chromosomes, with an extra chromosome 21. The mothers’
karyotypes are normal. A nondisjunction during meiosis, occur-
ring for unknown reasons, is held responsible for the disorder.
2. Nondisjunction occurring after fertilization in any cell division
results in mosaicism, a condition in which both normal and triso-
mic cells are found in various tissues.
3. In translocation, a fusion occurs of two chromosomes, usually 21
and 15, resulting in a total of 46 chromosomes, despite the pres-
ence of an extra chromosome 21. The disorder, unlike trisomy
21, is usually inherited, and the translocated chromosome may be
found in unaffected parents and siblings. The asymptomatic carri-
ers have only 45 chromosomes.
Approximately 6,000 babies are affected with Down syndrome in
the United States, which makes the incidence of Down syndrome 1 in
every 700 births, or 15 per 10,000 live births. For women older than 32
years of age, the risk of having a child with Down syndrome (trisomy
21) is about 1 in 100 births, but when translocation is present, the risk
is about 1 in 3. Most children with Down syndrome are mildly to mod-
erately intellectually disabled, with a minority having an IQ above 50.
Cognitive development appears to progress normally from birth to 6
months of age; IQ scores gradually decrease from near normal at 1 year
of age to about 30 to 50 as development proceeds. The decline in intel-
lectual function may not be readily apparent. Infant tests may not reveal
the full extent of the deficits. According to anecdotal clinical reports,
children with Down syndrome are typically placid, cheerful, and coop-
erative and adapt easily at home. With adolescence, the picture changes:
youth with Down syndrome may experience more social and emotional
difficulties and behavior disorders, and there is an increased risk for
psychotic disorders.
In Down syndrome, language function is a relative weak-
ness, whereas sociability and social skills, such as interpersonal
cooperation and conformity with social conventions, are rela-
tive strengths. Children with Down syndrome typically manifest
deficits in scanning the environment; they are more likely to
focus on a single stimulus, leading to difficulty noticing envi-
ronmental changes. A variety of comorbid psychiatric disorders
emerge in persons with Down syndrome; however, the rates
appear to be lower than in children with intellectual disability
and autism spectrum disorder.
The diagnosis of Down syndrome is made with relative ease
in an older child, but it is often difficult in newborn infants. The
most important signs in a newborn include general hypotonia;
oblique palpebral fissures; abundant neck skin; a small, flattened
skull; high cheekbones; and a protruding tongue. The hands are
broad and thick, with a single palmar transversal crease, and the
little fingers are short and curved inward. Moro reflex is weak or
absent. More than 100 signs or stigmata are described in Down
syndrome, but rarely are all found in one person. Commonly
occurring physical problems in Down syndrome include cardiac
defects, thyroid abnormalities, and gastrointestinal problems.
Life expectancy was once drastically limited to about the age of
40; however, currently it is vastly increased, although still not as
long as those without intellectual disability.
Down syndrome is characterized by deterioration in lan-
guage, memory, self-care skills, and problem-solving by the
third decade of life. Postmortem studies of individuals with
Down syndrome older than age 40 have shown a high incidence
of senile plaques and neurofibrillary tangles, similar to those
seen in Alzheimer’s disease. Neurofibrillary tangles are known
to occur in a variety of degenerative diseases, whereas senile
plaques seem to be found most often in Alzheimer’s disease and
in Down syndrome.
Fragile X Syndrome.
Fragile X syndrome is the second
most common single cause of intellectual disability. The syn-
drome results from a mutation on the X chromosome at what is
known as the fragile site (Xq27.3). The fragile site is expressed
in only some cells, and it may be absent in asymptomatic males
and female carriers. Much variability is present in both genetic
and phenotypic expression. Fragile X syndrome is believed to
occur in about 1 of every 1,000 males and 1 of every 2,000
females. The typical phenotype includes a large, long head and
ears, short stature, hyperextensible joints, and postpubertal
macroorchidism. Associated intellectual disability ranges from
mild to severe. The behavioral profile of persons with the syn-
drome includes a high rate of ADHD, learning disorders, and
autism spectrum disorder. Deficits in language function include
rapid perseverative speech with abnormalities in combining
words into phrases and sentences. Persons with fragile X syn-
drome seem to have relatively strong skills in communication
and socialization; their intellectual functions seem to decline in
the pubertal period. Female carriers are often less impaired than
males with fragile X syndrome, but females can also manifest
the typical physical characteristics and may have mild intellec-
tual disability.
Prader-Willi Syndrome.
Prader-Willi syndrome is believed
to result from a small deletion involving chromosome 15,
occurring sporadically. Its prevalence is less than 1 in 10,000.
Persons with the syndrome exhibit compulsive eating behavior
and often obesity, intellectual disability, hypogonadism, small
stature, hypotonia, and small hands and feet.
