Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.3 Intellectual Disability

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.

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-