Developmental disorders have a wide variety of causes, and few have a specific, identifiable genetic or neurobiologic etiology. Different etiologies converge on identical
behavioral phenotypes. The diagnostic yield is much greater if there is associated microcephaly, antenatal toxin exposure, or focal findings (19). In their absence, a thorough search for diagnostic clues includes family history with a three-generation pedigree and information from the prenatal, perinatal, and early postnatal periods. The development of motor skills; comprehension of speech; emergence of words and formed, intelligible sentences; and quality of social play skills are often relevant. The physical examination includes measuring head circumference as well as body size and growth; assessment of vision, hearing, and ocular funduscopy; searching for facial, skeletal, somatic, and dermatoglyphic anomalies and asymmetries; visceromegaly; neurocutaneous lesions and depigmentations; and other signs of chronic illness. Hand preference and pencil grip are noted as well as any abnormal postures and involuntary movements. Clinical clues in the evaluation of developmental disorders are presented in Table 18.2.

The mental status examination assesses the child’s orientation, relatedness to, and interest in the examiner, caregiver, siblings, peers, and other people in the child’s environment; the quality of reciprocal social exchange in verbal and nonverbal communication (e.g., eye contact, gestures, facial expression), ability to engage in reciprocal imaginative play with representational toys; presence of perseverative, stereotypic, and ritualistic behavior; and presence of problematic behaviors such as attention difficulties, overactivity, aggression, and self-injury.

The laboratory evaluation of choice for developmental disorders continues to evolve as increasingly detailed understanding of the human genome leads to improved delineation of syndromes and advances in cytogenetic,
molecular, and neuroimaging techniques. Routine test batteries are not effective. The incidence of identifiable metabolic disorders in children with developmental delay is low, ranging from 0% to 5% (20,21). In addition, nonspecific, nondiagnostic, or false-positive “abnormalities” are common in routine nondirected laboratory testing. This can lead to further futile laboratory pursuits. Most infants and children with inborn errors of metabolism show signs or symptoms of their metabolic disorder such as hepatosplenomegaly, failure to thrive, intolerance of certain food groups, intermittent emesis, recurrent unexplained illnesses, seizures, intermittent somnolence, or fluctuating hypotonia. The relevant metabolic tests are reviewed in Chapter 1. In patients with developmental disorders who lack signs or symptoms of a metabolic disorder, metabolic screening should be deferred (22,23,24).

Many individuals with mental retardation have associated behavioral, emotional, and psychiatric disorders and nonneurologic congenital anomalies. A composite pattern recognition or cytogenetic testing may lead to a specific diagnosis (25). In these circumstances, the diagnostic label refers to the most salient aspect of the condition or is noted by an acronym, such as CHARGE association (of congenital anomalies) or eponym (e.g., Angelman syndrome), or by the underlying chromosomal abnormality, such as at chromosome 22q11.2. A specific molecular cytogenetic analysis, such as fluorescence in situ hybridization (FISH), may be indicated if the child has features of a known mental retardation syndrome (e.g., Williams or fragile X syndrome) or autism (e.g., chromosome 15q11 duplication) (see Chapter 4).

In most individuals with mild mental retardation, there are no specific neuropathologic correlates. Neuroimaging has a low diagnostic yield unless there are suspicious physical findings or localized neurologic deficits (26). Delayed myelination visualized on magnetic resonance imaging (MRI) is nonspecific in infants and children with neurodevelopmental delays (27). The diagnostic yield of neuroimaging increases considerably if the mental retardation is severe or complicated by microcephaly or macrocephaly, major motor abnormalities, features of a genetic syndrome, or seizures. MRI may reveal migrational disorders (e.g., lissencephaly), midline defects (e.g., holoprosencephaly or septo-optic dysplasia), or other brain malformations and disruptions (e.g., schizencephaly) (see Chapter 5). When the history suggests metabolic insult, vascular compromise, infection, or trauma, neuroimaging may reveal evidence of destructive central nervous system (CNS) changes.

There is no consensus on which children with developmental delay should be studied by imaging, and there are considerable variations in technique, methodology, demographics, and interpretation between the few available studies of computed tomography (CT) and MRI in children with mental retardation. Correspondingly, the reported frequency of abnormal neuroimaging findings in persons with mental retardation ranges from 9% to 80% (28,29,30,31). Positron emission tomography (PET), single photon emission CT (SPECT), functional MRI (fMRI) (32), and volumetric and morphometric MRI (33) provide insights into specific conditions but have limited overall application in the infant or child with a nonspecific developmental disorder. Formal audiologic testing is required to rule out hearing loss in all children who have language delay and may have isolated high-frequency hearing losses. Children with hearing impairment should be followed longitudinally for speech therapy and possible speech amplification.

Electroencephalography (EEG) is indicated if the history suggests seizures or regression or plateau in language acquisition (see Chapter 14). EEG can assist in the diagnosis of certain children with developmental disorders (34). Seizure disorders are often in their own right associated with diminishing IQ, as is their treatment with antiepileptic drugs (see Chapter 14). Memory may be deficient when the seizures are generalized. In complex partial seizure disorder, verbal and nonverbal memory may be impaired when there are left and right foci, respectively (35). Epileptic children as a group have inferior attention and general slowing of mental processes (36) as well as a varying degree of lag in language and reading ability (37). Children with frontal epileptic foci exhibited a relatively greater degree of impulsivity and disordered planning, verbal fluency, and motor coordination than generalized and temporal comparison groups (37). A comprehensive treatment of the neuropsychology of childhood epilepsy is available (38).

In habilitation, rehabilitation techniques are applied to individuals who, rather than having lost previously mastered skills, failed to master new skills at the expected age. This applies to children with developmental delay. For purposes of habilitation, the physician is less concerned about the level of function, and more with the implementation of evidence-based effective and enabling therapies, regardless of etiology. Schools are the primary venues of such therapies, and the consensus is swinging toward ever stricter demand for evidence-based justifications for such educational practices. For example, the Federal Department of Education maintains a “What Works Clearinghouse” that periodically reviews and reports educational efficacy evidence that meets high standards (39).

Children who are considered to have cognitive deficiency may come to attention because of poor academic achievement, abnormal behavior, or both. Is the lack of academic achievement due to limited cognitive ability, or does it represent underachievement relative to the child’s potential for other (e.g., psychosocial or emotional) reasons? If the child appears to be achieving at his or her
maximum level, consistent with that child’s specific profile of cognitive or attentional strengths or weaknessess, then special needs are identified, and an individualized educational plan (IEP) is implemented. If the child is underachieving, the causes are sometimes found in the child’s school and social setting or emotional well-being. In only a few developmental syndromes, notably attention-deficit hyperactivity disorder (ADHD), can cognitive potential be enhanced by medical means. In particular, there is as yet no evidence that learning disabilities, distinct from any comorbid attentional disorder, are pharmacologically treatable.

Most disorders of mental development are long lasting, if not permanent. Whether the child’s condition declares itself at or before birth or during early childhood, the parents have to adjust their previous expectations of a perfectly healthy child to the current reality. This adjustment is traumatic, and not all parents navigate its difficulties with success. The problem is amplified if, as is commonly the case, a specific diagnosis as well as a specific prognosis cannot be formulated. Such opinions as “developmental disability” convey confusion and are no substitute for the clarity and credibility of a specific diagnosis. When the disability is chronic and not fully explained—for instance, as in mental retardation and in autism—the quality of the parent–child relationship may suffer for lack of clarity about what to expect in the future. The clinician cannot always persuade the parents of what appears to be the reality of the situation, or even of the diagnosis, when that can be ascertained. Continued uncertainty is detrimental to parent–child attachment as well as to the functioning of the family unit. Under such circumstances, encouragement to seek a second opinion can with advantage be accompanied by referral for psychological counseling.

The Education for All Handicapped Children Act (EHA) was renamed the Individuals with Disabilities Education Act (IDEA) in 1990. This legislation requires schools to provide an appropriate individualized educational plan to students with disabilities, to be implemented in the “least restrictive environment.” The IDEA mandates a nondiscriminatory assessment, active involvement of parents in the educational process with due-process rights and hearing, and access to indicated ancillary services such as physical therapy, counseling, and transportation. The reauthorization of IDEA requires that students with disabilities be educated with their nondisabled peers to the extent possible, and that schools actively plan for student transitions (and that traumatic brain injury and autism be considered separate categories). The word handicapped in the original version of the law was replaced with the word disabled. Inclusion refers to the effort to include students with disabilities in general classrooms while providing special services outside the general classroom as needed. Currently, approximately 70% of all students with disabilities attend mainstream classes during part of the school day.

In infancy and early childhood, receptive and expressive language and play skills are the best indices of cognitive level. The prognostic reliability of cognitive testing improves when children reach an age at which some language competence is expected and a wider range of testing modalities becomes available. Language development up to age 3 years can initially be documented in the clinical setting with the Early Language Milestone Scale (40). Early cognitive and language developmental milestones in infancy and childhood are summarized in Table 18.1.

The diagnosis of a cognitive deficiency requires that a clinical impression be validated by standard psychometric assessment or referral report. The assessment that is appropriate for infants and children with developmental delays or disabilities depends on the child’s age, level of impairment, and the presence of additional sensory deficits. For clinical screening up to age 6 years, the Denver-II, formerly the Denver Developmental Screening Test–Revised (41), has been commonly used. The Denver-II draws on parent history, testing, and observation and takes approximately one-half hour to administer. However, for predictive value, the Battelle Developmental Inventory Screening Test (BDIST), which screens children up to age 8 years, is preferred (42) though it is not designed to identify specific learning disabilities. A trained infant psychometrist is likely to adminster the Bayley Scales of Infant Development II, which estimate the level of cognitive and motor deficits in infants (43). However, because infant cognition is limited, only sensorimotor functions can be evaluated accurately for normative purposes. These functions are nonspecifically correlated to an infant’s later emerging cognitive skills, the lack of which may result in a developmental disability in later years. More specific information about selective deficits in cognitive operations can be gleaned from the results of neuropsychologic testing. A cognitive profile is established for diagnoses and functional evaluation, the monitoring of further development, and rehabilitation planning. Some commonly used measures of cognitive and adaptive behavioral development are summarized in Table 18.3.

Administered with proper reservation, an IQ test is by far the most valid means toward establishing a child’s level of functioning—knowledge that has wide clinical application. Regardless of disagreements as to whether IQ is a valid measure of intellectual or educational potential (58), the IQ test result is unequivocably the best guide in estimating overall current levels of functioning. IQ within the normal range by definition eliminates mental retardation

as the reason for preschool or school achievement below the expected level. It does not exclude the possibility that specific learning disabilities are compromising the acquisition of some academic skills. Therefore, IQ has been withdrawn from the necessary definition of learning disability in the 2004 IDEA. Furthermore, no single IQ test measures all cognitive operations, and various subtests involve multiple cognitive processes. Therefore, a low score on a subtest would be unlikely to isolate the basic cognitive deficit that prevents the child from learning to read, write, or calculate.

Some “scatter” between the levels of subscale or subtest scores on an intelligence scale is normal. Only when it is statistically excessive might it reflect a disparity in the level of development of different intellectual skills. Verbal-performance discrepancy scores are often reported. Children with mild mental retardation tend to score somewhat lower on the Wechsler verbal subscale than on the performance subscale. A much lower verbal than performance IQ accompanies selective language delay; the converse discrepancy is often found in association with developmental difficulties in spatial orientation and visuomotor control, and to some extent in Asperger disorder.

The Stanford-Binet scale (46) and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (44) are most commonly used for preschoolers. The Wechsler Intelligence Scale for Children (WISC-III) is available for school-aged children (45). These are well-standardized test batteries that call for the use of a range of different cognitive skills. For deaf children, the WISC-III performance scale and the Hiskey-Nebraska Test of Learning Aptitude have been specifically standardized (59). On such tests, deaf children without additional disabilities score close to the population average. The Perkins-Binet (60) and the Blind Learning Aptitude Test (61) are suitable for blind children. However, the most widely used psychometric instruments lack sensitivity in the mental retardation range. Even simple tests that use single words, such as the Peabody Picture Vocabulary Test (56), cannot be used if the patient is nonverbal. The Leiter International Performance Scale is useful for evaluating low functioning individuals (50). The interpretation of psychometric findings in mentally retarded subjects is complicated by uncertainties about the child’s test orientation and motivation. Because IQ levels in children younger than 3 years are unstable, the low-scoring child should receive a more definitive evaluation at a later date.

The developmental history and physical findings in early infancy are unreliable bases for prognosis as to developmental outcome. For example, Apgar scores of 0 to 3 at 15 and 20 minutes are predictive of high mortality and high probability of disability; however, many of these infants score normally in later developmental assessment (see Chapter 6). Intelligence tests in infancy yield a developmental quotient (DQ) that is necessarily heavily loaded with factors that relate to motor development. Within a normal population, the DQ is a poor predictor of individual differences in cognitive development. It has some success, however, in distinguishing a normally functioning from a mentally retarded population. Infant testing is highly specialized and also calls for the child’s cooperation. If this cannot be enlisted, the mother can be asked standard questions about her child’s social development (53).

Taken literally, the IQ scores can underestimate the child’s cognitive potential. Specific adaptive limitations often coexist with strengths in other adaptive skills or other personal capabilities. Limitations in adaptive skills may reflect the context of the child’s community. Motivation to perform during testing cannot be taken for granted, particularly when the child’s cultural or ethnic background has little understanding of and interest in cognitive testing and its uses. Anxiety can block the child’s reasoning processes, alienation and withdrawal can render the child unavailable for the task, thought disorders can intrude, and impulsive behavior can disrupt test performance. Lapses of attention owing to subclinical absence seizures can interrupt concentration, and psychotropic and antiepileptic medication may impair some cognitive processes. The limited attention span of patients with ADHD can degrade performance on tasks that demand sustained attention and cognitive effort. In young children, even gross impairment of vision, hearing, or touch can go unrecognized, and the child’s imperfect response to instruction or questions can be misattributed to defiance or cognitive deficiency. Other factors that complicate the interpretation of mental test performance are extremely low or high parental educational level, poor motivation with failure to expend mental effort on the test, depression, fatigue, and fear of failure with low self-esteem. Such potential sources of misinterpretation, which almost always lead to underestimation rather than overestimation, can never be fully ruled out, but conventional best practices expect the psychologist’s report, usually in writing, to provide an estimate of the reliability of the reported score, taking such factors into consideration.

The terminology that is used to characterize persons with cognitive and adaptive behavioral disabilities has evolved, in repeated efforts to minimize social stigma. Terms such
as cognitive deficiency, intellectual disability, and learning disability have been suggested to replace mental retardation, a term that misleadingly implies delay and therefore the possibility that the child will catch up. A similar term is developmental delay, which is nonspecific and is more of a chief complaint or a symptom complex than a diagnosis (62). Whereas children with mental retardation may learn new skills as they mature and are taught, most functional neurologic impairments are associated with intractable deficits of intellectual capacity. Mental retardation is a compendium term that does not refer to particular groups of diseases, syndromes, or medical disorders. It is not applied to cognitive deficiency that is a result of neurodegenerative and progressive neurometabolic diseases, or is secondary to psychiatric disorders.

The World Health Organization (ICD-10) characterizes developmental disabilities as due to impairment of the central nervous system, causing a functional disability, which consequently handicaps the individual in activities of daily living (63). It characterizes mental retardation as “incomplete or insufficient general development of mental capacities.” Formal definitions of mental retardation that are currently recognized emphasize a descriptive diagnosis of persons with significant disability because of “subaverage intellectual functioning” and “concurrent deficits or impairments in present adaptive functioning [i.e., how effective persons are in meeting the standards expected for their age by their cultural group]” (64,65). In addition, the manifestation of brain dysfunction must originate during the developmental period of life. The three formal definitions differ slightly in their approach to the diagnosis because of differences in emphasis on adaptive skill symptom menus or underlying etiologic factors.

Because mental abilities are on a continuum, the quantitative definitions of mental retardation and its subdivisions based on the IQ are necessarily arbitrary cut-off points. The mental age (the age equivalent at which the child functions on the test) divided by the chronologic age is the IQ. The mean I.Q. for the general population is set at 100. Higher IQ predicts more academic success in such terms as higher grades, more years completed, and higher standardized test scores. It also predicts positive life outcomes, such as better mental health, lower divorce rate, lower level of criminality, and greater occupational success (66,67).

The standard deviation (SD) of a test refers to the distribution of scores around the mean. Mild, moderate, severe, and profound mental retardation have been traditionally associated with cutoff points in standard deviations below the mean of –2, –3, –4, and –5, respectively (68) (roughly corresponding to IQs of 70, 55, 40, and 25). IQ scores between 70 and 85 are sometimes referred to as borderline. But measured intelligence does not offer specific information about the individual’s adaptive skills (Table 18.4). There is ongoing controversy on whether to emphasize IQ level or adaptive behavioral deficits as the central defining characteristic of mental retardation (69). The extent to which persons with mental retardation succeed in life is determined by their level of adaptive skills rather than by their IQ. However, there is no single measure of
adaptive behavior. Newer efforts to define mental retardation have emphasized the amount of support needed for an individual to succeed or maintain basic activities of daily living, instead of focusing on global degrees of impairment (70). Support intensities are subdivided into four levels: intermittent, limited, extensive, and pervasive. Support functions are classified into eight categories: teaching, befriending, financial planning, behavioral support, in-home living assistance, community and school access and use, and health assistance. This categorization acknowledges that the diagnosis of mental retardation is useful only as a pointer toward providing the individual with additional supports for activities of everyday living beyond those that are considered to be customary for the child’s age.

Further insight into the child’ strengths and weaknesses is afforded by neuropsychological testing, which attempts to tease out of the cognitive spectrum different domains of functioning that can be differentially affected by brain damage, depending on which areas have borne the brunt of the insult. These techniques are most frequently used with normal functioning children who have school problems but also can be applied to mildly mentally retarded children. The resulting information may be helpful with respect to diagnosis, prognosis, and educational and vocational planning (e.g., 71). IQ labeling should not replace repeated educational and achievement assessments. Not only is the IQ score unreliable below age 3 years, but also deficits in visual, spatial, and motor function, as well as expressive language, may influence early testing. Underprivileged and understimulated children may perform poorly on language-based tests for reasons that are sociocultural rather than neurobiological. Such a child’s level of functioning is better reflected in the results of nonverbal testing, as on the Culture-Fair Intelligence Test, Scale 2 (72), Raven’s Progressive Matrices (73), and the Universal Nonverbal Intelligence Test (74). The interpretation of IQ test results should take into account cultural and linguistic diversity, differences in communication ability, and attentional and behavioral factors.

A syndrome is a recognizable and consistent pattern of multiple manifestations that are known to have a specific etiology (75). More than 1,000 defined syndromes involve multiple congenital abnormalities (76). Most feature some pattern of impaired mental development. The degree of mental retardation is quite variable in most of these syndromes and is not indicated by the severity of neurobiologic concomitants, such as degree of abnormality of brain structure as visualized on MRI. Also, the deficit is often compounded by social factors. Dysmorphic facial features may give a misleading impression of low intelligence, and severe neurologic handicap may limit the children’s ability to express their intellect. Striking instances are athetosis and Lesch-Nyhan syndrome. Teachers may underestimate the child’s learning potential and offer a restricted number of learning opportunities. Nonetheless, some syndromes are characterized by specific behavioral phenotypes—of cognition, personality, and psychopathology—over and above the generally diminished level of functioning and any negative effects of the child’s environment.

Behavioral phenotypes have been characterized as follows, “a number of conditions, recognizable by a common physical phenotype, single gene defect or chromosomal abnormality, seem also to have a constellation of behaviors or cognitive anomalies which are characteristic” (77). Although mentally retarded children are by definition impaired in all or most cognitive domains, certain mental retardation syndromes present striking cognitive and behavioral dissociations. Selective neuropsychological deficits can occur against a background of generally deficient intellect as well as in otherwise normally functioning children. The adverse influence, whether genetic or due to intercurrent insults, is widespread, but lowering the level of intelligence below normative expectations, is not homogeneous, perhaps reflecting unequal impact on areas of the brain that differ in functional specialization. Examples of dissociations follow.

Mentally retarded children with autism are disproportionately handicapped in the language and social domains, domains that are relatively spared in children with Williams syndrome (78 and see Chapter 4). Children with Williams syndrome speak with appropriate phonology and syntax, although their comprehension and pragmatics are weak (see Chapter 4). However, they are especially deficient in visual-spatial construction and number sense. Conversely, visuospatial skills are a strong point for children with Prader-Willi syndrome, who display a specific flair for jigsaw puzzles (79). Down syndrome children are particularly impaired in receptive and still more in expressive language, long-term memory (80,81), and gross and especially fine motor skills (82). Particularly with respect to language, these impairments become more obvious after the initial relatively rapid development of the first three years has decelerated. Some Down children become autistic, especially if there is an autistic spectrum disorder family history (83). Girls with Down syndrome as a group consistently perform better than boys (84). Children with hydrocephalus tend to be disproportionately strong in speech production, producing rapid uninformative “cocktail chatter,” though not in speech comprehension and pragmatics. They are weak in face recognition and social cognition (85). Among X-linked chromosomal aberrations, fragile X syndrome (85a) is particularly handicapping in language development and social skills (86). Speech development is delayed, perseverative, and echolalic, and the children are
shy, anxious, and show many autistic features. There is fine and gross motor delay. The language and social domains also are problematic for children with XXX (87), whereas Turner syndrome (XO) is associated with visuospatial, arithmetic, and memory deficits (88) as well as deficient recognition of faces and facial expressions (89), while language is intact. XYY syndrome is characterized behaviorally by language disability, lack of sociability and aggressiveness, and Klinefelter syndrome (XXY) boys tend to exhibit low verbal abilities, clumsiness, and introversion (90). In Cornelia de Lange syndrome, nonverbal abilities may be selectively impaired (91). Untreated, phenylketonuria results in severe mental retardation. Even when effectively treated, children with phenylketonuria exhibit impaired performance on executive function tests (92), apparently implicating dopaminergic projections to dorsolateral prefrontal cortex (93). The characterization of the selective deficit as involving executive functions is disputed, however (94). Untreated children with congenital hypothyroidism are severely mentally retarded. After early treatment, deficits are confined to the domains of visuospatial skills, attention, and fine motor control (95). In galactosemia, language and executive impairments as well as fine motor deficits have been reported. Some of the children are mentally retarded (96).

It is apparent from the highly diverse listing presented above that deficits in cases of atypical development are not interpretable in terms of selective loss with respect to a single behavioral module or a single functional domain. Rather, there is a suite of more impaired domains, and a suite of better functioning domains, in every type of affected child. The cognitive phenotypes associated with a specific genetic abnormality also can be quite diverse, as for instance in Williams syndrome (97). Therefore, the phenotypes even of genetically determined syndromes appear to be multiply determined, with some effect of environment, in the broad sense that encompasses both prenatal and postnatal factors, interacting with the genetically determined susceptibility. Notably, language ability does not fall out or remain intact in one piece (98). The classical dispute about whether language skill is modular and unique among cognitive skills (99) is not resolved by the study of atypical development.

Persons with mental retardation are at increased risk for psychiatric disorders. Whereas the incidence of psychiatric disorders in the general childhood population is 7% to 10% (100), approximately one-third of all children with developmental disorders also have psychiatric disorders (100,101,102,103). In the severely retarded subpopulation, the frequency of psychiatric disorders is much higher and approaches two-thirds by adolescence (104). The broad spectrum of psychopathology includes affective disorders (105), anxiety disorders, autisticlike behaviors (106), conduct disorders (107), maladaptive behaviors (repetitive self-stimulation, self-injurious behavior, pica) (108,109), and psychosis. These emotional and behavioral disturbances are caused by multiple factors, both primary psychopathologies and neuropsychologic disorders and the secondary effects of illness, dependency, environmental deprivation, frustration, and low self-esteem (110).

The behavioral phenotypes of certain genetic syndromes are associated with typical personality characteristics and reproducible behavioral mannerisms (Table 18.5). Though otherwise often of even temperament, Down syndrome children may be irritable and inattentive because they are prone to obstructive sleep apnea (120), which in turn is a separate risk factor for neurocognitive (especially right hemisphere) deficits (121) and for depression (122). Specific personality differences also may occur in mental retardation syndromes, such as unusual sociability and distractibility in Williams syndrome and compulsivity, excessive talkativeness, impulsivity, and low activity level as well as compulsive eating and foraging for food in Prader-Willi syndrome (79).

Children with velocardiofacial syndrome have on average a borderline IQ, concrete thinking, bland affect, and little social interaction. They are highly susceptible to
psychiatric disorders, particularly schizophrenia, with which they may have a frequently occurring deletion on chromosome 22 in common (123). Twenty-five percent of children with velocardiofacial syndrome present with schizophrenia by early adulthood. A higher proportion still presents with ADHD in childhood and responds favorably to stimulant therapy (124). Girls with Turner syndrome tend to be unassertive and compliant and maintain poor and sparse social relationships (125). Children with Lesch-Nyhan syndrome have a unique form of compulsive behavior, which is expressed by an apparently involuntary drive toward self-injury and aggression. The children apologize and ask to be restrained in the act of attacking others or themselves (126). Abnormal dopamine functioning during early development may be implicated (126).

Since the frequency with which a disorder arises in a population during a stated period of time is its incidence, and since its prevalence describes the amount within a population at a given time, the prevalence of the condition is the product of its incidence and its duration. The prevalence of a developmental disorder, therefore, may change over the years because of prenatal diagnosis and more frequent termination of pregnancy, changes in the maternal population, and changes in health care. For example, the prevalence of Down syndrome increased from the 1920s through the 1960s, as persons with this condition began to live much longer because of improvements in medical care. However, since 1980, further increases have been slight (127,128).

The prevalence of mental retardation is 6 to 20 per 1,000 (129,130,131,132). The published estimates vary on account of regional differences, ascertainment biases, and variations in diagnostic criteria and study methodology. Mild mental retardation is 10 to 12 times more common than severe retardation. Mental retardation is more common among males because of X-linked syndromes involving mental retardation, especially fragile X syndrome. The male to female ratio ranges from 1.3:1 to 1.9:1 (133). Morbidity and mortality are greater in persons with severe mental retardation, not due to the mental retardation itself, but because of the severe cerebral palsy that is often associated with it. Total immobility and feeding by nasogastric tube are the features that are most predictive of curtailed life span (134,135).

As a psychopathology, autism is profoundly internalizing. The children are deeply preoccupied with their internal states of mind and feeling and only minimally engage the outside world for purposes of activities of daily living. The majority of children with autism are to a varying degree atypical even at an early age, moving and crying little, averse to being held, and content to be alone. Scales that assist earlier diagnosis are available, and home videos reviewed retrospectively can reveal a previously unsuspected onset during infancy (315,316). The children may reject solid foods, and toys elicit little interest or are held onto with unusual obstinacy. Their motor development is usually normal, but minor physical anomalies are more frequently found in autistic children than in controls (317). During the second year of life, children with autism are typically unusually sensitive to auditory, visual, tactile, and movement stimulation, and repetitive mannerisms or gestures begin to appear. The older child with autism has restricted and stereotyped behaviors and activities and markedly impaired creativity, social relations, language, and perception. Disturbances in social relations are manifested by poor or absent eye contact and a lack of interest in people, whom the child uses instrumentally rather than interactively. Toys are handled bizarrely or are dropped when handed to the child. Mannerisms include repetitive, stereotyped movements, such as hand flapping, ear flicking, or head banging (318). Toe walking, whirling, and rocking also are common. These movements, often complex, increase when the child is anxious or is confronted with a novel situation (319).

Language disturbances can consist of complete lack of speech, failure to communicate by pointing, failure to imitate (320), perseveration, echolalia (repeating words or phrases out of communicative context), and lack of reciprocity in dialogue (321). If speech does develop, its prosody is often monotonal, pronouns are used poorly, and humor is not understood. Speech in children with autism differs qualitatively from the speech of children with mild mental retardation. Within the limits of a restricted vocabulary, children with mild mental retardation typically speak normally, whereas children with autism use abnormal prosody, syntax, semantics, and pragmatics (322). In some children, termed hyperlexic, mechanical reading skills develop out of proportion to spontaneous verbal expression or reading comprehension (323,324).

Children with autism may be oversensitive to stimuli, notably self-created sounds or spinning objects (325). This oversensitivity can alternate with periods of nonresponsiveness to speech, objects, or pain. Affected children frequently ignore sounds and are “aloof,” provoking testing for possible hearing loss. Some have prolonged attention spans during self-initiated activity (326). Observational studies demonstrate hyperselectivity of attention in children with autism (319). They focus exclusively on a single distinctive aspect of a display, while ignoring its other features. They are impaired in broadening the spatial spread of visual attention (326a). Conversely, the excel as compaud to their typical peers on tests that calls for local perceptual processing, in which context has got to be discounted. An example is the Embedded Figures Task (326b). The propensity of some people with autism to achieve savant status on very narrowly defined skells (326c) also reflects their narrow focus. Children with autism also have been shown to be impaired in perceiving faces, but not objects (327). People’s clothing was more salient to autistic children then their emotional expressions (328). They fail as compaud to age-matched peers in infering other
people’s perspectives and mental states, focusing narrowly on their own (326d).

Some children exhibit transitional or milder degrees of autistic behavior, within the PDD spectrum. After age 5 to 6 years, such behaviors may merge with those observed in mental retardation. Others deviate into childhood disintegrative disorder (329) or Asperger disorder (330). The natural history and outcome of autism is variable. Some 80% manifest a pronounced impairment in intelligence. Approximately one-third of children with autism do not develop communicative speech. Others develop rudimentary language, although their communication remains literal and concrete and their affect flat. In yet other affected children, characteristics of organic brain disease become apparent over subsequent years, including auditory or visuoperceptual impairment. A small subset of children with autism develops bizarre thoughts and even delusions. About 75% of children who fail to show language skills by age 5 years fail to adjust personally or socially. Other children with autism make a fairly adequate social adjustment but retain certain peculiarities of personality, lack of humor, and unawareness of social nuances (331). Neuropsychologic testing reveals deficits on problem-solving tasks (332). Standard diagnostic instruments include the ADI (332a) and the ADOS (332b). Early diagnosis is facilitated by the use of standard instruments such as the Checklist for Autism in Toddlers (CHAT) (333). It consists of nine questions asked of the parents, and five items that call for observation by the clinician. The latter include pointing and looking to where a parent is pointing and pretend play, activities that are available to a normal 18 month old. Approximately one-half of the population with autism have an IQ above 50, and one-fourth to one-third have an IQ above 70. Children who regressed into autism after initially developing normally generally are ultimately more impaired cognitively (312,334). Even when they are enrolled in treatment programs, only some children with ASD improve significantly. If children improve, they usually do so during the second half of their first decade.

Based on twin studies, autism is thought to have the heaviest genetic loading of the chief developmental disorders, with more than 50% hereditability for the narrowly defined autistic disorder (335), and as much as 90% for the wider range of ASD (336). Moreover, autistic individuals rarely reproduce (337). Autism would therefore be expected to have a stable incidence. On the contrary, its prevalence across the ASD spectrum has risen from 2 to 4 in 10,000 children in the 1970s to 60 in 10,000 children in recent years, that is, 0.6% of the population (338,339,340,341,342,343,344,345). The rate of increase in autism is highest in developed countries, in the United States among children of American rather than immigrant mothers, and for autistic children who are high-functioning (346). It has been argued that the rise in prevalence is due to relaxation in diagnostic criteria, diagnostic substitution [e.g., ASD diagnosis substituted for Developmental Language Disorder (DLD) diagnosis—(346)], changes in and increasing availability of special education services, mandatory notification of ASD diagnoses, and increasing awareness and earlier recognition of ASD. However, the rise in incidence is so worldwide that it cannot be attributed to regulatory changes in just one country. Potential alternative causes and a true rise in incidence are not mutually exclusive, and the explanatory power of the alternative factors is open to challenge (347,348). No published research has managed to determine how much of the variance in the spectacular increase in ASD diagnoses is attributable to each of the various factors that have been suggested. Pending such information, it is unwarranted to assume that the true incidence of ASD is not increasing.