When assessing speech development, the nurse should refer which child for further revaluation?

Paediatr Child Health. 2003 Jul-Aug; 8(6): 345–356.

Language: English | French

Abstract

Mental Retardation (MR) is a problem encountered in almost all paediatric clinical settings. The assessment of a child with MR is a common diagnostic and management dilemma for paediatricians. The field of MR research is currently in a state of flux regarding not just our understanding of the condition, but also in the language and the processes we use in naming, defining and describing MR. This article will provide a better understanding and a rational approach toward MR. Prevalence rates for MR are variable in the literature and may be attributable to the variation in major classification systems and the diversity in study operation definitions and methodologies. Etiologies of MR are diverse and include many different influences. MR most often presents during infancy or preschool years as developmental delay. There is no universally accepted approach to the etiological work-up of mental retardation. The number of medical conditions associated with MR that are completely treatable by medical means remains small. The paediatrician plays a key role establishing short and long term treatment goals, as well as providing support to families who have children with MR.

Keywords: Children, Developmental delay, Mental retardation

Résumé

Le retard intellectuel (RI) est un trouble observé dans presque toutes les cliniques de pédiatrie. Le RI constitue un diagnostic courant et un dilemme de prise en charge pour le pédiatre. La recherche sur le RI est en effervescence non seulement pour ce qui est de notre compréhension de la pathologie, mais également pour ce qui est du langage et des processus utilisés pour nommer, définir et décrire le RI. Le présent article permettra de mieux comprendre le RI et d’utiliser une démarche rationnelle face au RI. Les taux de prévalence du RI sont variables dans la documentation scientifique et peuvent être attribuables à la variation des divers systèmes de classification ainsi qu’à la diversité des définitions et des méthodologies utilisées pour mener les études. Les étiologies du RI sont diverses et incluent de nombreuses influences. La plupart du temps, le RI se présente pendant la première enfance ou l’âge préscolaire sous forme de retard de développement. Il n’existe aucune démarche universelle face au bilan étiologique du RI. Le nombre de troubles médicaux associés au RI qui sont entièrement traitables par des moyens médicaux demeure faible. Le pédiatre joue un rôle de premier plan dans l’établissement des objectifs de traitement à court et à long terme, ainsi que dans le soutien aux familles.

OBJECTIVES

1. Be familiar with the common presentations and causes of mental retardation (MR).

2. Be able to approach the ‘work-up’ of a child with suspected MR in a logical and efficient manner.

3. Gain an appreciation for the importance of a correct diagnosis of MR in a patient, for both the child and the family.

INTRODUCTION AND DEFINITION

MR is a problem encountered in almost all paediatric clinical settings. It is the final common pathway of various pathological processes that alter the functioning of the central nervous system. The field of MR research is currently in a state of flux regarding not just our understanding of the condition, but also in the language and the processes we use in naming, defining and describing MR. The name assigned to this condition varies internationally, and other related terms include ‘general learning disorder’, ‘intellectual disability’ and ‘intellectual impairment’ (1,2). There is ongoing discussion about changing the name from MR to one that better portrays those affected. However, at the present time no consensus has been reached. Therefore, in this paper, MR will be used in reference to this condition.

MR was defined by the American Association on Mental Retardation (AAMR) in 1992, as an intellectual disability, existing concurrently with deficits in two or more of the following applicable adaptive behavioural skill areas: communication, home living, community use, health and safety, leisure, self-care, social skills, self-direction, functional academics, and work (3). Since its publication, the 1992 classification system has generated healthy debate, discussion and critiques. The results of these activities have culminated in a new definition. The 2002 definition of MR by the AAMR has three components: MR is a disability; MR is characterized by significant limitations in both intellectual functioning and conceptual, social, and practical adaptive skills; and MR must manifest before the end of the developmental period defined as the first 18 years of life (4). The following assumptions are essential when applying this new definition of MR. First, a valid assessment should take into account cultural and linguistic differences in communication and behavioural factors. Second, any assessment should focus on an individual’s performance during normal daily routines and changing circumstances, and not on the person’s best performance.

Though far from perfect, intellectual functioning is still best represented by intelligence quotient (IQ) scores obtained from appropriate assessment instruments. Performance of two SDs below the mean of a corresponding group of people (for example, in age, culture and context) on an intelligence test is usually required to make the diagnosis. This correlates to a score of less than 68 on the Stanford-Binet, fourth edition (SB: IV) or below 70 on one of the Wechsler tests (ie, Wechsler Preschool and Primary Scale of Intelligence, Revised [WPPSI-R]; Wechsler Intelligence Scale for Children, third edition, Wechsler Adult Intelligence Scale, third edition). It should be noted, however, that both the SB: IV and WPPSI-R are limited in terms of their usefulness in establishing a diagnosis of MR in children three years of age and younger (5). This is because at the earliest year levels of the test, the floor (ie, the lowest possible score that can be obtained) results in a higher IQ score than at the later year levels. For example, on the WPPSI-R, the lowest possible Performance IQ score at three years is 66, and the lowest possible Verbal IQ score is 71, whereas at age five years the lowest possible Performance IQ is 47 and the lowest possible Verbal IQ is 48. As a result, in young, low functioning children, decreases in IQ on standardized measures from three to five years of age may not indicate a serious decrement in functioning. Rather, they may be a reflection of how the test was constructed. Therefore, if a young child fails most or all of the items on the SB: IV or the WPPSI-R, further assessment of the child’s functional abilities is warranted.

Classification of individuals with MR has been divided into ‘mild’ (IQ 50 to 55, to 70 to 75), ‘moderate’ (IQ 35 to 40, to 50 to 55), ‘severe’ (IQ 20 to 25, to 35 to 40) and ‘profound’ (IQ below 20 or 25) (6). When there is significant scatter in the subtest scores, the profile of strengths and weaknesses, rather than the mathematically derived IQ may be a more accurate reflection of the person’s cognitive abilities.

In this review, we will be presenting information on children with mild MR versus children with severe MR. This differentiation of MR into mild and severe categories may seem to be somewhat of an artificial separation. However, most of the published literature on the epidemiology of MR divides the population of individuals with MR into these two groups. In the newest AAMR definition, the classification of severity of MR has been replaced by the concept of intensity of support required. Such a classification is thought to be more functional and oriented to service delivery and outcomes (1).

In the following sections of this article, select studies drawn from the clinical and research literature that addressed MR and its diagnosis are presented. Most of the studies referenced have been published during the past decade. Further, none of these studies relating to the investigation of MR were undertaken in a primary care setting.

EPIDEMIOLOGY

A review of 33 studies conducted after 1963, predominantly from western industrialized countries, showed prevalence rates for mild MR ranged from 3.2 to 79.3 per 1000 and for severe MR from 2.8 to 7.3 per 1000 (7). While this variation in estimates of prevalence across countries and regions may represent some true differences, it is also largely attributable to the variations in the classification of MR and methodologies used by different studies (1). The most recent literature estimates an incidence of mild MR at 10.6 per 1000 and severe MR at 1.4 per 1000 (1). This is consistent with a recent study using a national survey of 46,000 households in the United States that found the prevalence of MR in the noninstitutionalized population to be 7.8 people per 1000 (8). MR has been found to occur more frequently in boys with a male to female ratio of 1.6 to one supporting the notion that an X-linked pattern of inheritance underlies a significant proportion of cases of MR (9,10). Mild MR tends to be familial or polygenic compared with severe MR, which tends to be sporadic. Severe MR has no socioeconomic, racial or geographic predilection.

ETIOLOGICAL CONSIDERATIONS

Etiologies of MR are diverse and include many different influences. A survey of physicians referring patients with MR to subspecialists has shown that a high priority is given to determining the cause of MR (11). Determining such etiology can be useful in counselling families about prognosis, recurrence risks and preferred modes of available therapy.

Malnutrition is probably the most common cause of mild MR worldwide, in conjunction with sociocultural deprivation and other problems related to poverty (12). In developed countries, the underlying causes of MR are various and heterogeneous and can remain unknown in up to 66% of cases (10). Gillerot et al (13) identified a subgroup of the population with MR (66% of a sample of 500 children affected by mild MR) that was thought to have ‘sociocultural handicap’ due to lack of stimulation in childhood. This suggests that in a significant proportion of children, mild MR is associated with growing up in a deprived environment.

Stromme and Hagberg (14) studied 178 children with MR derived from a population-based series of 30,000 children born between 1980 and 1985 in Norway. Forty-four per cent of these children had severe MR (IQ less than 50) and 56% had mild MR (IQ 50 to 70) as presented in Table 1. Monogenic and chromosomal disorders were more frequent in the severe MR group, whereas, less specific deficits were associated with mild MR. Prenatal factors were implicated more often than perinatal or postnatal factors combined.

TABLE 1

Classification of etiology of 178 children with mental retardation (MR)

Noteworthy, a study conducted in Atlanta, Georgia, of children born in the mid-1970s revealed that low birth weight was associated with a two-to fourfold increased risk for MR (15). Despite substantial changes in neonatal management in the interim, the smallest infants are still at increased risk for developing mild and severe MR. Finally, a recent longitudinal follow-up study of 242 very low birth weight infants (those weighing less than 1500 g) born between 1977 and 1979 found that they had lower mean IQs than controls. Interestingly, approximately 7% to 8% of these very low birth weight infants were found to be within the MR range on IQ testing (16).

SYNDROMES ASSOCIATED WITH MR

There are a number of syndromes that have a particular genetic etiology that typically have associated morphological and/or behavioural phenotypes, and are associated with MR (Table 2). Down syndrome is the most common with an incidence of one in 650 to 1000 live births (17). Some conditions occur predominantly in boys (eg, Fragile X and Coffin Lowry) (18,19). In a Norwegian population-based series, X-linked recessive conditions occurred in six of 63 (9.5%) children with a genetic cause for their MR (14). Other conditions, such as Rett syndrome, occur predominantly in girls (20). Fragile X syndrome is the most frequent form of inherited MR accounting for 1% to 6% of MR in boys (21). Angelman syndrome was found to account for 1.4% of the moderately to profoundly mentally retarded subjects screened for this syndrome in one study (22). About one-third of individuals with Noonan syndrome have a mild intellectual disability with an average IQ 10 points below that of unaffected family members (23).

TABLE 2

Common syndromes associated with mental retardation (MR)

Some studies suggest that fetal alcohol syndrome (FAS) is the most common cause of MR among children in the United States (24–26). The literature on the prevalence of FAS is far from consistent. The occurrence of FAS can range from 0.6 to three per 1000 live births in most communities, with some communities (eg, inner city regions and people of African American or Native American background) having an increased prevalence (26,27). People with FAS can have IQs from well within the normal range to the severely mentally retarded range. On average, individuals with the full syndrome have mild MR with IQ scores in the 60s (27). Physical anomalies can be slight or quite striking. Table 3 presents the clinical features of FAS (27). Learning difficulties, poor attention, hyperactivity and adaptive functioning problems that grow more significant as the child matures have also been described with FAS.

TABLE 3

Clinical features of fetal alcohol syndrome (FAS)

It is well recognized that children who have been exposed to alcohol antenatally may be at risk for the primary and secondary disabilities associated with antenatal alcohol exposure even if the physical phenotype is normal. For this and other reasons, different groups have attempted to create accurate, reproducible tools for diagnosing FAS and related conditions. One such approach is the University of Washington 4-digit diagnostic code (28). This approach attempts to score the magnitude of expression of four key features (growth deficiency, facial phenotype, brain dysfunction and gestational alcohol exposure) in a reproducible manner. The end result is 22 possible unique clinical diagnoses (ranging from FAS, alcohol exposed to no cognitive, behavioural or sentinel physical findings detected, no alcohol exposure). These specific diagnoses can then be better used for educational planning, advocacy, reporting and research.

DISORDERS ASSOCIATED WITH MR

MR is also associated with a number of disorders. In this context, ‘disorder’ refers to a condition associated with an abnormality of function. Up to 30% of cases of MR are associated with epilepsy and/or cerebral palsy. Epilepsy has consistently been shown to be the single most common disorder associated with MR (in 15% to 30% of cases) (9). Cerebral palsy is a static disorder of motor function that occurs as a result of injury or abnormal morphogenesis of the motor region of the immature developing brain. It is found in approximately 20% to 30% of patients with MR (9). Sensory impairments (visual and hearing), psychiatric disorders and language deficits are also common among individuals with MR. Further, the co-occurrence of these disorders tends to increase with the severity of retardation.

Central nervous system malformations are present in some patients with MR (21). This can include neural tube defects and hydrocephalus. In a study of 60 patients with MR, 10 (16.7%) had cerebral dysgenesis such as cerebellar hypoplasia, agenesis and/or hypoplasia of the corpus callosum, and heterotopia (11). Neuronal migrational disorders, such as lissencephaly, and defects of cortical organization, such as polymicrogyria and schizencephaly, often present with MR along with other features, such as seizures, spasticity and microcephaly.

Other neurological conditions to be considered include neuromuscular disorders and neurocutaneous syndromes, such as tuberous sclerosis (TS) and neurofibromatosis type 1 (NF-1). One-third of patients with Duchenne muscular dystrophy can have mild to moderate MR (12). Approximately 45% to 60% of individuals with TS have mental disabilities (29). Seizures occur in 60% to 90% of individuals with TS. The degree of intellectual dysfunction ranges from very mild to severe. Individuals whose seizures continue after treatment and those with a large number of cortical tubers have a much greater likelihood of mental disability. MR occurs in 2% to 5% of patients with NF (30).

Autism is a neurobehavioural syndrome characterized by pervasive and severe deficits in verbal and nonverbal communication and social skills, and includes the presence of abnormal repetitive and stereotyped behaviours. It has been widely documented that the majority of individuals with autism also have MR. Bryson et al (31) reported that approximately 75% of their Canadian sample had IQs below 50. Ritvo and Freeman (32) found that 60% of individuals with autism had IQs below 50, 20% had IQs in the range 50 to 70 and only 20% had measured IQs above 70. There is a higher incidence of autism in boys, with one study (33) of 97 children finding 79.4% to be boys. It has also been established that, on average, the mean IQ scores of groups of girls with autism are slightly lower than for groups of boys with autism (34,35). Further, in the very severe and profound ranges of retardation, the sex ratio of males to females has been found to shift from 4.1 to 2.5, to 3.0 to 1. This suggests that there is an excess of girls with autism in the severe range of MR (34). Bailey et al (36) observed, however, that autistic disorder is also noted for some strengths in cognitive skills, or ‘islets of ability’, as well as a specific pattern of deficits. Visual-spatial abilities are usually better in autistic individuals, often resulting in a higher Performance IQ score than Verbal IQ score and, hence, an uneven cognitive profile.

While certain behavioural and cognitive features may be over-represented in all patients with MR, it is important to know that specific behavioural patterns may be associated with certain genetic syndromes. Recognizing these so-called ‘behavioural phenotypes’ may lead to the correct diagnosis of the underlying genetic syndrome, allowing for accurate genetic counselling and anticipatory care. Examples include: the over-friendliness and anxiety of children with Williams syndrome (37); the self-injurious or self-stimulatory behaviour and severe sleep disturbances of children with Smith-Magenis syndrome (38); the obsessions and compulsions of children with Prader-Willi syndrome (39); or the social anxiety, sensory defensiveness and hyperactivity of boys, and some girls, with Fragile X syndrome (40). Specific molecular or molecular cytogenetic tests exist for these and many other genetic syndromes associated with recognizable behavioural phenotypes.

In addition to the above disorders, studies have reported significant psychiatric morbidity in individuals with MR. Hoare et al (41) found that 38% of 143 children with severe disability had significant psychiatric morbidity. Psychiatric disorders such as depression (including bipolar affective disorder), psychosis and anxiety disorders (including obsessive compulsive disorder and phobias) were noted. Behavioural problems were also reported to be prominent in another study. They included problems in feeding, elimination, sleeping, hyperkinesis, hypokinesis, stereotyped behaviours, self-injurious behaviour and licking. Further, these behaviours were closely associated with cognitive development level (42).

CLINICAL ASPECTS OF THE DIAGNOSIS

MR most often presents during infancy or preschool years as developmental delay. Other presentations may include congenital hypotonia, seizures, feeding problems, or other symptoms associated with CNS malformations. Milder forms of MR may not be picked up until the school years. Impairments in adaptive functioning, rather than low IQ, are the usual presenting features. Lack of communication skills may predispose to disruptive and aggressive behaviours. Therefore, careful attention to the rate of development in separate developmental streams in children is very important.

The history, including pre-, peri-and postnatal features, could assist in determining an etiology. The use of prescribed medications and other drugs during pregnancy should be closely reviewed. Consumption of an average daily alcohol volume of one or more drinks during pregnancy has been associated with an increased risk of FAS and related disorders (43). A rash or fever during the pregnancy should raise the possibility of a congenital infection. Recurrent unexplained illness, seizures or loss of psychomotor skills raise the possibility of a metabolic disorder. Childhood human immunodeficiency virus-related encephalopathy may also present with unexplained illnesses and global impairment of cognitive and social functioning (44). Gathering a careful family history is essential in the etiological search of MR. A three-generation pedigree, paying attention to unexplained deaths in infancy and/or childhood, recurrent fetal losses, learning problems, psychiatric disorders, nonspecific developmental problems, autism and MR in relatives as well as inquiring about consanguinity, is mandatory.

When MR is suspected, the child should always have a complete physical examination. A thorough physical examination helped to determine a diagnosis in 22 of 120 patients (18.3%) in one study (45). Such an examination should incorporate a review of growth parameters (including head circumference) and the skin (looking at neurocutaneous stigmata, abnormal pigmentation and dermatoglyphics) (29,46). Dysmorphic features looking especially at the face, hands and feet and genitalia can be suggestive of aneuploidy. This is particularly the case if there is reduced family resemblance. The presence of three minor anomalies and/or unusual appearance helped to make a diagnosis of MR in one Canadian series (47). Finally, a detailed neurological examination should always be performed.

Clinical photographs may be useful to document and follow findings. A behavioural phenotype may be apparent after observing cognitive, language and social skills during the consultation. Audiological assessment and an ophthalmological review can supplement the initial clinical examination. Information from other sources (eg, past health records, teacher reports) may also be of help.

Obviously, the need for referral depends on the comfort and competency of the primary practitioner to take the history outlined above and elicit the appropriate clinical findings. Access to and familiarity with the investigations, which are outlined below, will also play a role in the decision of whether to refer. A number of recent reports have highlighted the beneficial role played by subspecialist involvement (be it by a neurologist, geneticist or developmental paediatrician) in the diagnosis and management of MR (47,48).

INVESTIGATIONS

There is no universally accepted approach to the etiological work-up of developmental delay and MR (49). A consensus conference using available literature and expert opinion sponsored by the American College of Medical Genetics in 1995 attempted to identify some consensus recommendations and is summarized in Table 4 (50). Selective laboratory testing in most patients should include a karyotype at the 500-band level, especially if the diagnosis is not apparent. Chromosomal abnormalities are one of the most common causes of MR (10). The severity of MR and presence of congenital anomalies has been thought to increase the yield of abnormality (50).

TABLE 4

Key features of management of mental retardation (MR)

Fluorescent in situ hybridization (FISH) allows the detection of gain and/or loss of genetic material from 0.1 megabases. FISH probes exist for such disorders as Williams syndrome, Velocardiofacial syndrome, Smith-Magenis syndrome and some cases of Prader-Willi and Angelman syndromes. Such microdeletion syndromes represent cytogenetic alterations not observed in a routine karyotype. These probes should be considered when clinically indicated (Table 2). It is important to remember that if FISH testing is ordered, you must specify which disorder is under consideration. Direct diagnosis by DNA analysis for Fragile X was described by Rousseau et al (51). It should be considered in both boys and girls with unexplained MR, especially in the presence of a positive family history, or a suggestive physical or psychiatric phenotype (50). It has been argued that screening for Fragile X in all patients with idiopathic MR would result in the detection in 0.6% to 14% of the cases, even if there were no features to suggest the diagnosis (21). There is debate, however, about whether Fragile X screening can be refined with screening checklists (47,52).

Neuroimaging should be considered in patients without a known diagnosis especially in the presence of focal neurological abnormalities, cranial contour abnormalities, macrocephaly, or microcephaly (50). Shevell et al (48) found that imaging studies performed for a specific indication (eg, microcephaly) were more than three times as likely to result in an etiological yield than when done on a screening basis. The magnetic resonance imaging (MRI) scan is superior to the computed tomography (CT) scan because it provides more accurate images of the structures of the posterior fossa and of maturational differences in the brain including myelination. A higher rate of abnormality detected by MRI compared with CT has been observed in the literature (47). There is also lack of exposure to ionizing radiation. The CT scan is useful, however, for conditions associated with intracranial calcifications and suspected craniosynostosis. Neuroimaging is not required in known syndromes unless there are additional neurological signs not consistent with the diagnosis.

Careful analysis of brain neuroimaging, combined with a detailed history and physical examination, enables clinicians to establish etiological links and insights into the developmental brain problems associated with MR. Recent investigations have reported that high intensity lesions on T2-weighted images and hyperintense lesions on T1-weighted images could be disease specific abnormalities for NF-1 (53). Although the significance of such lesions and their relationship to clinical features such as MR has not been established, this is an example of how imaging techniques are shedding new insights into conditions associated with MR (54). It remains controversial, however, whether neuroimaging is indicated in all cases of NF-1.

It has been argued that routine metabolic screening should be abandoned because of its low yield in the work-up of MR (48). Endocrine and metabolic causes of MR accounted for only 0.8% of causes of MR in a survey of children born in California (10). This figure is in agreement with a recent Australian study that showed the diagnostic yield of urine amino and organic acid screening tests to be 1.1% for patients with ‘developmental delay’ or ‘intellectual disability’ (55). The authors of this study (55) argue that despite the low diagnostic yield, these investigations should still be strongly considered. Specific therapies were available for 69% of the diagnoses and 87.5% had known Mendelian or mitochondrial inheritance. It is argued that the expense of these investigations is outweighed by the early diagnosis of inborn errors of metabolism. Such benefits include early therapeutic intervention, assisting couples in making reproductive decisions and the potential reduced costs to society with respect to the long term supervised care that affected individuals may require as adults.

Certainly, if the clinical picture suggests such a cause (eg, growth failure, hypoglycemia or acidosis), then metabolic studies are mandatory (Table 5). Such a screen would include screening the urine (amino acids, organic acids, complex and simple sugars and mucopolysaccharides) and blood (plasma amino acids, serum lactate and serum ammonia).

TABLE 5

Features to suggest a metabolic disorder

In addition, other metabolic investigations that may be considered depending on the scenario could include very long chain fatty acids, serum 7-dehydrocholesterol and total cholesterol, thyroid function studies, lactate to pyruvate ratios and cerebral spinal fluid studies (lactate, amino acids and glucose). These latter investigations should not be considered ‘routine’ in the investigation of MR.

A creatinine phosphokinase may be fruitful in boys in the preschool years presenting with developmental delay, particularly, if there are concerns about gross motor skills given the association of MR with some forms of muscular dystrophy such as Duchenne. Congenital infection accounted for 0.4% of the patients with MR in the study by Croen et al (10). Serology, however, is not useful in diagnosing such infections beyond the newborn period.

Battaglia et al (45) found a relatively high diagnostic yield (8.3%) in the group of patients they assessed using electroencephalogram (EEG). The use of EEG should be considered in any patient with seizures and/or epilepsy. Seizures often coexist with Rett and Angelman syndromes. Table 6 summarizes the investigations outlined above and is in keeping with “Evaluation of mental retardation: Recommendations of a Consensus Conference” (50).

TABLE 6

Investigations recommended in work-up of mental retardation

Despite all of the tests at our disposal, the majority of cases of MR, even when there is a presumed ‘genetic’ origin, remain unexplained. For this reason, new technologies are being developed. At present, one exciting new test modality is the ability to screen for subtelomeric chromosome deletions. The telomeres are the gene-rich ends of the chromosomes. It is now recognized that a significant proportion (perhaps 7% to 10%) of unexplained MR is actually due to small deletions or rearrangements of the chromosomes at the telomeres that cannot be seen by routine cytogenetics. The results of such tests are of clinical importance because occasionally the parents may be carriers of ‘cryptic’ subtelomeric rearrangements and would be at risk for further affected offspring (56). While these tests are not yet widely available, these and other tests should become more accessible on a clinical basis within the next few years. It remains to be seen whether specific checklists may help triage which patients should be studied using these techniques (57).

It should be noted that most of the studies cited were performed by subspecialists (eg, neurologists, developmental paediatricians or geneticists). Therefore, general paediatricians may be unlikely to undertake such investigations. However, it is useful for them to be aware of the above tests and procedures so that they can refer patients who may be appropriate. While some studies of investigations of MR in children have been retrospective chart reviews (45,47), there have also been some prospective studies conducted (48). All these studies have confirmed that the most important aspect of any evaluation remains a thorough history and physical examination (49). It can be argued that laboratory investigations should be used in a ‘directed fashion’ rather than as ‘screening’ tools (49). This was the case in the study by Shevell et al (48) where physicians did not follow a specified template, but rather used their own discretion when ordering tests. However, this makes it difficult to generalize the yield of such tests to all populations (49). It has been suggested that a multisite, protocol-driven study would be of value in obtaining a degree of uniformity in investigations carried out and hence allow some estimation of the yield of the investigations outlined above.

MANAGEMENT

The aims of paediatric management are to provide support to people with MR and their families and to assist them in creating personally satisfying lives (Table 4). It is vital that the practitioner not fail to diagnose specific syndromes or treatable genetic conditions. Patients with MR, along with their families, benefit from a directed clinical and laboratory evaluation aimed at establishing etiology, as outlined in the preceding paragraphs. This in turn provides a focus for education about the diagnosis and counselling about prognosis. Paediatricians must be aware, however, that most causes of MR are not treatable directly. Nevertheless, accurate diagnosis may aid in genetic counselling, and alleviate parental guilt. More importantly, even if an etiological diagnosis cannot be made, the provision of sound advice and emotional support from both the primary physician and sometimes from other parents (through support groups) can assist in planning for future needs.

While few details of the consultation in which a diagnosis (or lack thereof) will be remembered in later years, the way in which this information is conveyed may well be. In a study of 103 parents of children with severe physical disability, only 37% of parents were satisfied with how the disclosure was made (58). Key components leading to increased satisfaction in this study included a sympathetic and approachable manner, combined with direct and clear communication. A range of emotions and reactions from the parents is possible, ranging from wanting to be left alone to having questions answered immediately (59). Research has demonstrated that parents wish to be given as much information as early as possible and to be treated as the people primarily responsible for their child (60). Physicians can learn directly from parents and people with MR about the best way to communicate a diagnosis of MR. A summary of key components involved in informing parents about a diagnosis of MR are presented in Table 7.

TABLE 7

Key components in conveying a diagnosis of mental retardation (MR)

Recurrence risks, where appropriate, and guidelines for management, such as referral to appropriate services for therapy, education, financial and other support services should be addressed (50). Provision of accurate recurrence risk counselling depends on identifying the correct underlying diagnosis. If a specific diagnosis is reached, then the possibility for carrier testing or prenatal diagnosis may exist. In addition, the child with MR should personally receive recurrence risk counselling in adolescence or adulthood when appropriate. If a specific diagnosis cannot be identified, then it is appropriate to quote ‘empiric’ recurrence risk figures, which vary depending on the scenario (61).

It is important that the practitioner has an intricate knowledge of community resources for the family. Services will vary from province to province and may involve both government and subsidized agencies. Services for children of different ages may also be provided by different government departments. For the family of a child with MR, this array of services may be confusing. Obviously each family will have their own particular needs for their child but the United Nations has listed a number of services that governments should provide (62). This includes provisions discussed elsewhere including information, counselling and consumer or parent support groups. Other important services include financial assistance, equipment (at low cost), recreation or community access facilitation and, ultimately, vocational training. Respite care (often with other families) has been found to be an important resource for families of children with MR, particularly if the primary caregiver has some underlying distress (41). Further, it has been found to reduce the incidence of child maltreatment (63).

The medical practitioner also plays a crucial role in managing medical problems, such as those related to nutrition, epilepsy and spasticity. The incidence of feeding problems in those with MR has been estimated to be 33% in the literature (64,65). Anticipatory guidance on expected medical complications is also of benefit to the patient and family. There are now some excellent resources to help physicians and other healthcare professionals manage their patients who present with common syndromes. One such example is the textbook Management of Genetic Syndromes (66).

The number of medical conditions associated with MR that are completely treatable by medical means is small. The prototypical example is phenylketonuria (PKU). The profound MR and autistic features associated with untreated PKU can now be completely prevented by dietary manipulation. It is for this reason that newborn screening programs for PKU exist in virtually every jurisdiction. It is now recognized that treatment for PKU should continue life-long to prevent subtle effects on IQ and performance. It is also well known that women with a known history of PKU, or with a previously undiagnosed case of hyperphenylalaninemia, are at significant risk for having children with MR. For this reason, strict management is needed during pregnancy. In addition, consideration should be given to checking a mother’s plasma amino acids if she has children with MR and microcephaly with or without congenital heart disease (67). In other disorders associated with MR, specific therapies may help at least modify behavioural symptoms. The autosomal recessive disorder Smith-Lemli-Opitz (SLO) syndrome is caused by an inborn error of cholesterol metabolism. Replacement therapy with high doses of cholesterol is associated with improved growth in patients with SLO. Many of the behavioural manifestations of SLO may also improve with cholesterol therapy, however, the MR cannot be reversed (68). Some of the severe behavioural and sleep disturbances associated with Smith-Magenis syndrome respond to treatment with melatonin or beta-adrenergic antagonists (69).

Identification of developmental disabilities may enable children to be placed in an early intervention program. Such programs can promote development of language, physical, behavioural and self-help skills, and provide educational intervention to prepare the child for school (eg, applied behaviour analyses for children with autism, early speech and language therapy for children with significant language delays). During the school years, integrated programs with appropriate support can allow ongoing development. In the case of FAS, it is important to recognize that although children are affected by prenatal exposure to alcohol, a great deal of neurological development occurs postnatally and if child care, nutrition and the environment are adequate it is probable that children can make considerable progress. Adequate education and training, together with protection from negative child rearing environments and attention to predictable crises at various development stages, can make the difference between achieving a reasonable degree of independence and life satisfaction compared with other more negative outcomes (27). Similarly, intervention with children with autism has shown that these children can show improvements in their functioning regardless of the type of intervention (70). It has been argued that early guidance and monitoring of subjects and their families thought to have ‘sociocultural handicap’ due to lack of stimulation in childhood could have a large impact on the reduction of this condition (13). Thus, early educational and psychosocial intervention with all children with MR and their families could have a significant impact on the eventual outcome.

Repeat assessments, especially if a diagnosis has not been reached, are recommended as the phenotype (either physical or psychiatric) may develop over time. The features of many syndromes, such as Fragile X syndrome, are neither specific nor constant and can evolve over time. It is preferable to continue monitoring a patient rather than risk making a diagnosis that may need to be retracted at a later time. For such patients, annual evaluations until school age and a revaluation at puberty are considered to be appropriate, when possible (50). Fifteen per cent of children had their etiological diagnoses revised in one recent study (14). The ability to reach a diagnosis is also likely to increase slowly over time as newer molecular and/or cytogenetic techniques and improved intracranial imaging methods evolve. Evaluating the patient over time also allows a ‘step-wise’ rather than a ‘shotgun’ approach to investigations. Prognostic and reproductive counselling is also best done over a longer time frame.

One challenge for the paediatrician, related to the difficulty of making a definitive diagnosis of MR in a preschool child, is not to miss the ‘window of opportunity’ for early intervention.

The family environment can act as a source of strength or alternatively as a source of stress for a child with MR. Strutton (71) noted that a family member with MR brings to family members (be it father, mother, grandparent or sibling) different ways of coping with the changes. Research that has investigated parental coping has found that mothers of children with MR experience more stress and problems in psychosocial adjustment than fathers (72–75). In addition, both mothers and fathers are at higher risk for depression than parents of typically developing children (73). Investigations of siblings of children with MR suggest that they experience unique stresses. There is conflicting evidence about whether siblings receive less attention and possibly even fewer holidays and outings than their friends (71). Studies have also suggested that siblings of children with MR take on more caretaking responsibilities in the household than siblings of typically developing children (76,77). Many siblings may be unable to account for or understand their parent’s increased level of preoccupation, sadness or anger at the realization that a family member has MR (71). Further, siblings of children with MR may feel that their parents favour the disabled children (78). Some siblings, however, cope quite well with having a disabled sibling (80,81). Exploring the changed relationships that a child with MR brings to a family should not be neglected and requires time and expertise.

Despite the additional stress associated with having a child with MR, many families take on the responsibility of caring for the child (with MR) with love. Unfortunately, this is not always the case (71). There is evidence to suggest that siblings of children with MR are well adjusted (80). Krauss et al (81) found that this continues into adult life with a high level of contact between siblings with disabilities and siblings without disabilities. In one study, 41% of siblings without disability reported in-person visits to their sibling with a disability at least once a week or more, while 58% reported living within a 30-min drive of each other’s residence. Among the most commonly shared activities were going to a restaurant (63%), shopping together (56%) and going to the movies (44%) (81).

Behaviours associated with self-harm, harm to others, damage of property should be monitored for, as this will obviously hinder social interaction. Appropriate behavioural modification, such as applied behaviour analysis, may assist with such difficult behaviours(82). Any behaviour modification program will require a thorough description of the problem behaviours including possible triggering factors. Behavioural interventions are normally developed and implemented by a psychologist. The paediatrician can, however, provide support and assistance with the intervention plan. Modifications of such behaviours will reduce stress on the family, make it easier for participation in an educational and/or day program, and ultimately improve the chances of the individual being able to live in the noninstitutionalized community in the long term. All these facets will lead to improved quality of life. Inappropriate sexual behaviour can often be managed by changes in the environment, training of the care givers and behaviour programs. Such behaviour may lead to social isolation and lack of opportunity and should be anticipated at the time of puberty.

Restrictions in finances and time, and the lack of a clear alternative may add pressure to use medication to resolve the behavioural problem (83). While there are some situations where medication may result in improvement, there is no solid research evidence of their benefit (83). Certainly medication can be considered when there are unacceptable restrictions on the person’s lifestyle or stigmatization of that person within a community. Such therapeutic options may include beta blockers, psychotropics, and serotonin-selective reuptake inhibitors (SSRIs) (84). Risperidone, a psychotropic drug, has the advantage of not having the degree of sedation or parkinsonian adverse effects of the older psychotropics, but initial orthostatic hypotension is common (83).

Depression may be difficult to diagnose in people with developmental disability making a trial of an SSRI worth considering. Citalopram has been found to be a safe and effective antidepressant in mentally retarded subjects with depressive disorders (85). Aggression may sometimes be due to irritability associated with depression. SSRIs may have a beneficial effect due to both their antidepressant and anxiolytic effects on aggressive behaviour. Recently, fluoxetine has been found to modify aggressive behaviour even without proven depression (86). The response to treatment of any pharmacological treatment should be monitored regularly and weighed against any adverse effects. The temptation to continue increasing doses should be avoided at the expense of exploring other possible causes and management options of problem behaviours. Chemical restraint of such patients should be avoided at all costs. Finally, the involvement of child psychiatrists may be strongly considered especially with these above issues.

Most studies investigating stimulant medication in children with attention deficits excluded patients with MR, despite attention deficit and hyperactivity being common clinical problems in this group. Approximately 7% of mentally retarded children received stimulant medication in one series (87). There have been only a few controlled trials looking at the efficacy of stimulant medications in children with MR and attention deficit hyperactivity disorder (88). It is thought that children with an IQ between 45 and 75 respond in a similar way to children with a normal IQ, with improvements being observed in impulsivity, hyperactivity and attention deficits (88). Only minor effects were observed in social skills and academic performance. Stimulant response is much lower in children between four and five years of age, and is not recommended for those younger than three years. A positive effect of methylphenidate has not been documented in children with Fragile X syndrome or an IQ less than 45 (88,89). Finally, children with MR are at greater risk of developing side effects, with up to one in five children stopping therapy due to tics and social withdrawal (90). More research is needed in this area particularly looking at the efficacy of stimulants combined with a parent’s training program or behavioural modification program and the effects of stimulants on the long term course of MR.

When considering the management of children with MR, it is also important to consider the important role of preventive medicine. Vaccination against rubella infection can protect pregnant women and thus reduce the occurrence of multiple disabilities. Public education about the effects of environmental teratogens such as cigarette smoke, alcohol and other substance abuse is crucial. Neonatal screening programs can allow early treatment of conditions such as PKU and congenital hypothyroidism. Finally, genetic counselling can outline the risks involved to future children and allow parents to make an informed decision about whether to have any further children.

PROGNOSIS

An important role for the physician is to assist families in planning for the future of their disabled child. This includes the transition to adult medical care. The prognosis is in part determined by the underlying diagnosis or syndrome if found (6). Children with mild MR can often acquire social and vocational skills adequate for minimum self-support. They may need supervision and assistance, especially when under stress. Most individuals with moderate MR acquire communication skills during the early childhood years. They may learn to travel independently to familiar places and in their adult years are able to perform unskilled or semiskilled work under supervision in sheltered workshops or the general work force. Those with severe MR may learn to talk during the school years and can be trained in elementary self-care skills. In the adult years, they can perform simple tasks in closely supervised settings. Vocational support can provide dignified and productive work and leisure pursuits.

Most adults with severe MR will live in the community in group homes or with their families, unless an associated handicap requires specialized nursing or other care (91). The provision of community-based residential support for people with MR and their families may enable the person to remain a part of his or her community and avoid institutionalization. After reviewing the literature, Seltzer and Krauss (91) observed that most patients with MR (60%) live at home with their families as opposed to in institutions (15%). The important role of relationships with siblings and planning for care of adults who no longer have family has been noted in the literature (91). Features that may negatively affect the quality of life of adults who live at home include poor functional and cognitive abilities, more serious behavioural problems and nonparticipation in a day program. These features make it less likely for the adult to have friends or a sibling willing to become a caregiver. Adults with no explicit future plan for placement are at risk for emergency placements or placements not consistent with the parents’ wishes.

Individuals with MR who do not have appropriate supports are vulnerable to exploitation by others or being denied rights and opportunities. Access to advocacy can support the person with MR and the family and also press service providers and governments to respond appropriately to their needs. Enlightened policy and legislation can establish and support the rights of people with MR as citizens (92).

CONCLUSION

The key to managing children with MR involves four basic elements:

• Early identification.

• Determination of an underlying etiology (if possible).

• Prompt provision of rehabilitation or support services.

• Being an advocate for the parent(s) or caregiver (s) and helping them to advocate rights for their child.

This review has sought to provide a definition of MR and its severity. The assessment of a child with MR is a common diagnostic and management dilemma for paediatricians. The prevalence of mild MR varies inversely with socioeconomic status of the family, but moderate-to-severe MR occurs with equal frequency across all social classes. Therefore, diagnosis of MR includes a search for etiology in every case in childhood.

A number of etiologies should be strongly considered including chromosomal abnormalities, Fragile X syndrome and FAS. A thorough and careful delineation of the degree and profile of cognitive deficits and any associated dysfunctions should be done in all cases of suspected MR. The sociocultural and home environment should also be evaluated. There are a number of key points in the history (prenatal factors, family pedigree) and examination (skin, growth parameters, dysmorphisms, neurology) that may help point to a diagnosis or suggest the timing of the insult.

A banded karyotype and Fragile X molecular study should be strongly considered in all patients, particularly if there is a suggestive family history or no other apparent diagnosis. MRI of the head is the preferred mode of imaging but is not mandatory. However, it should be considered if there is abnormal head size or cranial contour, seizures, neurocutaneous stigmata or neurological findings. Metabolic screens and EEG are likely to have a low yield unless there are specific clinical indications, which were outlined above. The involvement of a sub-specialist (genetics, neurology or developmentalist) is likely to augment the above work-up and help with counselling about prognosis and recurrence.

Repeat assessments are quite beneficial, particularly if the diagnosis is not apparent. Anticipating possible medical complications and referral to appropriate agencies (therapy, educational, support, financial) early on is key to management. Long term planning, such as vocational training, living arrangements and medical care in the adult years, is also best started sooner rather than later. The paediatrician has a central role in establishing short and long term treatment goals, as well as providing support to families who have children with MR.

Acknowledgments

We would like to thank Brenda Greig for her support and assistance in the preparation of this manuscript.

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