Definition

Three criteria must be met to establish the diagnosis of intellectual disability: significantly subaverage intellectual function, significant impairments in adaptive function, and onset before 18 years of age. The three diagnostic formulations—Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), American Association on Intellectual and Developmental Disabilities (AAIDD), and Individuals with Disabilities Education Act (IDEA)—agree on the 3 criteria but define them differently.

Significantly subaverage general intellectual function refers to performance on an individually administered test of intelligence that is approximately two standard deviations (SD) below the mean. For a test that has a mean of 100 and SD of 15, IQ scores below 70 would meet these criteria. If the standard error of measurement is considered, the upper limits of subaverage intellectual function may extend to an IQ of 75. Using a score of 75 to delineate intellectual disability might double the number of children with intellectual disability, but the requirement for impairment of adaptive skills limits the false positives. Children with intellectual disability often show a variable pattern of strengths and weaknesses. Not all of their partial scores on IQ tests fall into the significantly subaverage range.

Significant impairment in adaptive behavior reflects the degree that the cognitive dysfunction impairs daily function. Adaptive behavior refers to the skills that are required for people to function in their everyday lives. Adaptive behavior may be assessed by three different constructs: the classification of DSM-IV-TR, the classification of AAIDD, and the IDEA.

The DSM-IV-TR classification of adaptive behavior addresses 10 domains: communication, self-care, home living, social and interpersonal skills, use of community resources, self-direction, functional academics, work, leisure, and health and safety. For a deficit in adaptive behavior to be present, a significant delay in 2 of the 10 areas must be present.

The AAIDD classification of adaptive behavior addresses 3 broad sets of skills: conceptual, social, and practical. Conceptual skills include language, reading and writing, money concepts, and self-direction. Social skills include interpersonal skills, personal responsibility, self-esteem, gullibility, naiveté, and ability to follow rules, obey laws, and avoid victimization. Representative practical skills are performance of activities of daily living (dressing, feeding, toileting and bathing, mobility), instrumental activities of daily living (housework, managing money, taking medication, shopping, preparing meals, using the telephone, etc) occupational skills, and the maintenance of a safe environment. For a deficit in adaptive behavior to be present, a significant delay in 1 of the 3 areas must be present. The rationale for requiring only 1 of the 3 areas is the empirically derived finding that people with intellectual disability can have varying patterns of ability and may not have deficits in all 3 areas.

The IDEA requires that the cognitive dysfunction affect school performance.

The requirement for adaptive behavior deficits is the most controversial aspect of the diagnostic formulation. The controversy centers on 2 broad areas: whether impairments in adaptive behavior are necessary for the construct of intellectual disability and what to measure. The adaptive behavior criterion may be irrelevant for many children; adaptive behavior is impaired in virtually all children who have IQ scores <50. The major utility of the adaptive behavior criterion is to confirm intellectual disability in children with IQ scores in the 65-75 range. It should be noted that deficits in adaptive behavior are often found in disorders such as Asperger syndrome (Chapter 28) and ADHD (Chapter 30) in the presence of typical intellectual function.

The issues of measurement are important as well. The independence of the 3 domains of the AAIDD and the 10 domains of the DSM-IV-TR has not been validated with research. The relationship between adaptive behavior and IQ performance is insufficiently explored. Most adults with mild intellectual disability do not have significant impairments in practical skills. It should be noted that adaptive behavior deficits must be distinguished from maladaptive behavior (e.g., aggression, inappropriate sexual contact).

Onset before age 18 yr distinguishes dysfunctions that originate during the developmental period. The diagnosis of intellectual disability may be made after 18 years of age, but the cognitive and adaptive dysfunction must have been manifested before age 18. The IDEA, because of its focus on school-aged children, does not require a limit of 18 years but refers to the “developmental period.”

The most commonly used medical diagnostic criteria for intellectual disability are those contained in the DSM-IV-TR (Table 33-1). The classification of intellectual disability that results from these definitions has been criticized for depending on IQ test performance rather than adaptive behavior, not taking the standard error of measurement into account, and not being predictive of outcomes for individuals. A new edition is currently being prepared that might address these issues. The AAIDD has proposed a different classification system. Instead of defining degrees of deficit (mild to profound), the AAIDD definition substitutes levels of support required in areas of adaptive function (intermittent, limited, extensive, or pervasive). The reliability of this approach has been challenged, and it blurs the distinction between intellectual and other developmental disabilities (communication disorder, autism, specific learning disabilities).

The term mental retardation should be cast aside because it is stigmatizing, has been used to limit the achievements of the individual, and has not met its initial objective of providing assistance to people with the disorder. The term intellectual disability is increasingly used in its place but has not been adopted universally; existing laws and their attendant entitlements still use the term mental retardation. In Europe, the term learning disability is often used to describe intellectual disability. Global developmental delay is a term often used to describe young children whose limitations have not yet resulted in a formal diagnosis of intellectual disability; it is often inappropriately used beyond the point when it is clear the child has intellectual disability, usually age 3 years.

Etiology

There appear to be 2 overlapping populations of children with intellectual disability: mild (IQ >50-70), which is more associated with environmental influences, and severe (IQ < 50), which is more frequently linked to biologic causes. Mild intellectual disability is 4 times more likely to be found in the offspring of women who have not completed high school than in women who have graduated. This is presumably a consequence of both genetic (children can inherit an intellectual impairment) and socioeconomic (poverty, malnutrition) factors. The specific causes of mild intellectual disability are identifiable in <50% of affected individuals. The most common biologic causes of mild intellectual disability include genetic or chromosomal syndromes with multiple, major, or minor congenital anomalies (velocardiofacial syndrome, Williams syndrome, Noonan’s syndrome), intrauterine growth restriction, prematurity, perinatal insults, intrauterine exposure to drugs of abuse (including alcohol), and sex chromosomal abnormalities. Familial clustering is common.

In children with severe intellectual disability, a biologic cause (most commonly prenatal) can be identified in >75% of cases. Causes include chromosomal (e.g., Down syndrome Wolf-Hirschhorn syndrome, deletion 1p36 syndrome) and other genetic and epigenetic disorders (e.g., fragile X syndrome, Rett syndrome, Angelman and Prader-Willi syndromes), abnormalities of brain development (e.g., lissencephaly), and inborn errors of metabolism or neurodegenerative disorders (e.g, mucopolysaccharidoses) (Table 33-2). Consistent with the finding that disorders that alter early embryogenesis are the most common and severe, the earlier the problem occurs in development, the more severe its consequences tend to be.

Table 33-2 IDENTIFICATION OF CAUSE IN CHILDREN WITH SEVERE INTELLECTUAL DISABILITY

CAUSE	EXAMPLES	PERCENT OF TOTAL
Chromosomal disorder	Trisomies 21, 18, 13, Deletion 1p36 Klinefelter’s syndrome Wolf Hirschhorn syndrome

∼20 Genetic syndrome ∼20 Nonsyndromic autosomal mutations Variations in copy number, Mutations in SYNGAP1, GRIK2, TUSC3 and oligosaccharyl transferase ∼10 Developmental brain abnormality Hydrocephalus ± meningomyelocele, lissencephaly ∼8 Inborn errors of metabolism or neurodegenerative disorder PKU, Tay-Sachs, various storage diseases ∼7 Congenital infections HIV, toxoplasmosis, rubella, CMV, syphilis, herpes simplex ∼3 Familial intellectual disability Environment, syndromic, or genetic ∼5 Perinatal causes HIE, meningitis, IVH, PVL, fetal alcohol syndrome 4 Postnatal causes Trauma (abuse), meningitis, hypothyroidism ∼4 Unknown Cerebral palsy 20

CMV, cytomegalovirus; HIE, hypoxic ischemic encephalopathy; HIV, human immunodeficiency virus; IVH, intraventricular hemorrhage; PKU, phenylketonuria; PVL, periventricular leukomalacia.

Modified from Stromme P, Hayberg G: Aetiology in severe and mild mental retardation: a population based study of Norwegian children, Dev Med Child Neurol 42:76–86, 2000.

Epidemiology

The prevalence of intellectual disability depends on the definition, the method of ascertainment, and the population. According to statistics (based on the DSM-IV-TR definition), 2.5% of the population should have intellectual disability, and 85% of these individuals should fall into the mild range. In 2005-2006, ∼556,000 or only 1.1% of school-aged children received services for intellectual disability in federally supported school programs in the US. For several reasons, fewer children than predicted are identified as having mild intellectual disability. Because it is more difficult to diagnose mild intellectual disability than the more severe forms, professionals might defer the diagnosis and give the benefit of the doubt to the child. Other reasons that contribute to the discrepancy are use of instruments that underidentify young children with mild intellectual disability, some children being diagnosed as having autism spectrum disorders and their intellectual disability not addressed, and a disinclination to make the diagnosis in poor or minority students because of previous overdiagnosis.

Young children might show cognitive limitations without significant delays in adaptive behavior. As a result, new cases of mild intellectual disability continue to be diagnosed among children up to 9 yr of age. Children with intellectual disability also may be incorporated into another diagnosis (e.g., autism, cerebral palsy). Furthermore, it is possible that the number of children with mild intellectual disability is actually decreasing as a result of public health and education measures to prevent prematurity and provide early intervention and head start programs. In fact, the number of school children who receive services for intellectual disability has not changed appreciably since 1997.

Unlike mild intellectual disability, where the prevalence may be decreasing, the occurrence of severe intellectual disability has not changed appreciably since the 1940s and is 0.3-0.5% of the population. Many of the causes of severe intellectual disability involve genetic or congenital brain malformations that can neither be anticipated nor treated at present. In addition, new populations with severe intellectual disability have offset the decreases in the prevalence of severe intellectual disability that have resulted from improved health care. Although prenatal diagnosis and subsequent pregnancy terminations have resulted in a decreased prevalence of Down syndrome (Chapter 76), and newborn screening with early treatment has virtually eliminated intellectual disability caused by phenylketonuria and congenital hypothyroidism, an increased prevalence of maternal prenatal drug use (Chapter 90.4) and improved survival of very low birthweight premature infants has counterbalanced this effect.

Overall, intellectual disability occurs more in boys than in girls: 2 : 1 in mild intellectual disability and 1.5 : 1 in severe intellectual disability. In part this may be a consequence of the many X-linked disorders associated with intellectual disability, the most prominent being fragile X syndrome.

Pathology and Pathogenesis

The limitations in our knowledge of the neuropathology of intellectual disability are exemplified by the fact that 10-20% of brains of persons with severe intellectual disability appear entirely normal by standard neuropathologic study. The majority of brains of these persons show only mild, nonspecific changes that correlate poorly with the degree of intellectual disability. These changes include microcephaly, gray matter heterotopias in the subcortical white matter, unusually regular columnar arrangement of the cortex, and neurons that are more tightly packed than usual. Only a minority of the brain shows more specific changes in dendritic and synaptic organization, with dysgenesis of dendritic spines or cortical pyramidal neurons, or impaired growth of dendritic trees.

The programming of the central nervous system (CNS) involves a process of induction; CNS maturation is defined in terms of genetic, molecular, autocrine, paracrine, and endocrine influences. Receptors, signaling molecules, and genes are critical to brain development. The maintenance of different neuronal phenotypes in the adult brain involves the same genetic transcripts that play a crucial role during fetal development, with activation of similar intracellular signal transduction mechanisms. Several syndromes that were thought to involve complex chromosomal abnormalities are, in fact, caused by single gene mutations involving induction. Rubinstein-Taybi syndrome (Chapter 76), a disorder marked clinically by broad thumbs and great toes, characteristic facies, and severe intellectual disability, has been shown to result from a mutation in the gene encoding for the transcriptional co-activator CREB binding protein (CBP), a factor important in the control of gene expression in early embryogenesis.

Clinical Manifestations

Early diagnosis of intellectual disability facilitates earlier intervention, identification of abilities, realistic goal setting, easing of parental anxiety, and greater acceptance of the child in the community. Most children with intellectual disability first come to the pediatrician’s attention in infancy because of dysmorphisms, associated developmental disabilities, or failure to meet age-appropriate developmental milestones. There are no specific physical characteristics of intellectual disability, but dysmorphisms may be the earliest signs that bring children to the attention of the pediatrician. They might fall within a genetic syndrome such as Down syndrome or be isolated, as in microcephaly or failure to thrive. Associated developmental disabilities include seizure disorders, cerebral palsy, hypotonia, and autism; these conditions are seen more commonly in conjunction with intellectual disability than in the general population.