Unintended Diagnosis of Von Hippel Lindau Syndrome Using Array Comparative Genomic Hybridization (CGH): Counseling Challenges Arising from Unexpected Information

Array Comparative Genomic Hybridization (array CGH) is a powerful tool for identifying genomic imbalances and providing a diagnosis in individuals with a normal karyotype. It has been particularly useful in the investigation of individuals with developmental delay +/?, dysmorphic features and/or multiple congenital abnormalities. However, this non-targeted method of scanning the whole genome can reveal unexpected information. We present a case where array CGH identified the cause of a proband’s moderate mental retardation by discovery of a de novo deletion of chromosome 3p25.3. This deletion was shown to contain at least 25 genes including the VHL gene, the deletion or mutation of which leads to Von Hippel Lindau (VHL) syndrome. Presymptomatic testing for VHL is usually offered after appropriate genetic counseling about the implications of this condition. Therefore, scanning the genome by array CGH presents a number of challenges for the genetic counselor. We suggest that further understanding of the psychosocial effects of array CGH is needed in order for appropriate pre- and post-test counseling to be provided.     

Genetics and educational psychology

Background: Molecular genetics, one of the most energetic and exciting areas of science, is slowly but surely coming to educational psychology. Aims: We review recent molecular genetic research on learning disabilities as a sign of things to come in educational psychology. We also consider some misconceptions about genetics that have slowed the acceptance of genetics in educational psychology. Samples: Diverse samples of children with learning disabilities have been studied, primarily in the UK and the USA. Methods: Linkage analysis can detect genes that have large effects on learning disabilities. Association analysis can detect genes of much smaller effect size, which is important because common disorders such as learning disabilities are likely to be influenced by many genes as well as by many environmental factors. Results: For reading disability, replicated linkages have been identified on chromosomes 6, 15 and 18. A gene responsible for a rare type of language impairment has recently been identified. For common language impairment, linkages on chromosomes 16 and 19 have recently been reported. More than 200 genetic disorders, most extremely rare, include mental retardation among their symptoms, and chromosomal abnormalities are a major cause of mental retardation. Conclusions: Although finding specific genes associated with learning disabilities is unlikely to have much of a direct application for teachers in the classroom, such findings will have far‐reaching implications for diagnosis, treatment and prevention of learning disabilities and for research in educational psychology. Educational psychology has been slower to accept evidence for the importance of genetics than other areas of psychology in part because of misconceptions about what it means to say that genetics is important for common complex disorders such as learning disabilities.     

Rubinstein-Taybi syndrome.

Rubinstein-Taybi Syndrome was first described in 1957 but only in 1963 as a distinguishable type of moderate mental retardation. The cause is still unknown although some type of genetic origin is possible. No consistent chromosomal abnormality has been demonstrated, the chromosomal analysis is normal, and cases are generally not considered hereditary. The recurrent risk for siblings is approximately 0.1% but may be as high as 50% for offspring of patients with the syndrome. The Rubinstein-Taybi syndrome is not at present detectable before birth and is evenly found in both males and females. The syndrome was thought to be rare but an increase in the number of reported cases each year suggests it is not as rare as estimated. It is thought to occur in about 1 in 300,000 births, and since it has become readily identifiable, more than 400 cases have been reported worldwide.     

Word-attack skills in individuals with mental retardation

This article assesses the state of the literature on word-attack skills and phonological awareness (PA) in individuals with mental retardation, in light of progress towards the development of effective teaching procedures. The literature contains promising findings. Studies have shown PA to be correlated with word-attack skills in individuals with mental retardation, as has been shown conclusively in typically developing children. This suggests that instruction in PA would facilitate the acquisition of word-attack skills in individuals with mental retardation, as it does with typically developing children. As of yet, however, very few experimental studies designed to demonstrate effective teaching procedures for PA and word-attack skills have been published. This research field might evolve most effectively and efficiently by following a two-step research program. First, test new teaching procedures in a series of small-N studies, each study incorporating modifications of teaching procedures based on the results of the previous study. Once procedures prove effective at this level, the resources necessary to pursue large-scale studies can be used to their best advantage.     

A METHODOLOGY FOR DISTINGUISHING BETWEEN EXTINCTION AND PUNISHMENT EFFECTS ASSOCIATED WITH RESPONSE BLOCKING

We present one method for distinguishing between extinction and punishment effects. The proportion of responses that produced a consequence (blocking) was varied while hand mouthing was treated in a man diagnosed with profound mental retardation. Response patterns across the schedule changes suggested that the blocking procedure functioned as a punishing event.     

Developmental psychology and mental retardation. Integrating scientific principles with treatment practices

The current debates about "best practices" within mental retardation reflect key unresolved issues about the nature of mental retardation and the goals of treatment programs. The central axiom proposed is that better integration of basic principles about human development with treatment practices for children will yield substantial benefits to individuals and society. To illustrate the format for this proposed integration, three principles have been abstracted from scientific inquiry in human development: (a) targeted environmental prevention, (b) metacognitive conveyance, and (c) ecological dominion. A contextual analysis, using special education as an example of a major treatment setting, indicates that application of these developmental principles is likely to reduce the prevalence of mild retardation (as currently defined), to minimize social and behavioral problems, and to foster improved levels of environmental mastery (adaptive success) for many children with low IQs and cognitive deficiencies. Consistent with these developmental principles, the current construct of mental retardation is judged inadequate, and an alternative diagnostic strategy is proposed. This strategy is based on repeated developmental profiling of a child and his or her biosocial environmental history.     

Brief report: Contact desensitization in the treatment of dog phobias in persons who have mental retardation

In comparison with the research done on phobias in non-retarded individuals, there is a paucity of research in the treatment of phobias in persons with mental retardation. In this study, contact desensitization was evaluated as a treatment for two individuals who have mental retardation and an intense fear of dogs. Following base-line assessment using a behavioral avoidance test (BAT) measuring actual approach behavior, treatment was implemented in a multiple base-line across subjects design. Contact desensitization resulted in the elimination of avoidance behavior in both subjects during the BAT. Measures of generalization in an outdoor setting, and maintenance during a two-month follow-up, showed that the clients continued to be free of avoidance behavior. The implications for further application and research are discussed.     

Delayed matching to two-picture samples by individuals with and without disabilities: an analysis of the role of naming

Delayed matching to complex, two-picture samples (e.g., cat-dog) may be improved when the samples occasion differential verbal behavior. In Experiment 1, individuals with mental retardation matched picture comparisons to identical single-picture samples or to two-picture samples, one of which was identical to a comparison. Accuracy scores were typically high on single-picture trials under both simultaneous and delayed matching conditions. Scores on two-picture trials were also high during the simultaneous condition but were lower during the delay condition. However, scores improved on delayed two-picture trials when each of the sample pictures was named aloud before comparison responding. Experiment 2 replicated these results with preschoolers with typical development and a youth with mental retardation. Sample naming also improved the preschoolers' matching when the samples were pairs of spoken names and the correct comparison picture matched one of the names. Collectively, the participants could produce the verbal behavior that might have improved performance, but typically did not do so unless the procedure required it. The success of the naming intervention recommends it for improving the observing and remembering of multiple elements of complex instructional stimuli.     

An 8q21 deletion in a patient with comorbid psychosis and mental retardation

Systematic investigations indicate that some of the recognized psychiatric disorders can be identified among those with mental retardation due to chromosomal abnormalities. We report a psychotic patient with mild mental retardation (intelligence quotient: 68) and minor anomalies that had a chromosomal aberration not previously described in a psychotic patient. Our patient highlights the importance of the cytogenetic study in psychiatric patients with comorbid mental retardation or minor anomalies. In addition, her psychosis symptoms may be helpful to propose a new candidate gene for psychosis.     

Health-promoting physical activity of adults with mental retardation

This literature review describes the physical activity behavior of adults with mental retardation consistent with the U.S. Surgeon General's recommendation of 30 minutes of moderate intensity physical activity on 5 or more days per week. The proportion of participants achieving this criterion ranges from 17.5 to 33%. These data are likely to be generous estimates of activity as individuals included in physical activity studies to date have been relatively young and healthy volunteers with mild to moderate limitations. Major sources of physical activity were walking and cycling for transport, chores and work, dancing, and Special Olympics. There is a pressing need to conduct studies using appropriately powered representative samples and to validate measures that assess physical activity less directly; including methodologies in which proxy respondents are used. Accurate information about existing patterns of behavior will enhance the development of effective strategies to promote physical activity among persons with mental retardation.     

BEHAVIORAL ASSESSMENT OF FEEDING PROBLEMS OF INDIVIDUALS WITH SEVERE DISABILITIES

As many as 80% of the individuals with severe or profound mental retardation exhibit feeding problems. Although behavioral interventions have been used to treat these problems, no assessment procedure for determining a functional relationship between a person's acceptance of food and the type and texture of that food has been reported. The purpose of this study was to test a behavioral assessment procedure for a feeding problem of limited intake. Five individuals with severe or profound mental retardation were fed 10 to 12 types of foods with one or more textures. Behavioral categories of acceptance, rejection, expulsion, and other negative behavior were recorded. Results indicated that each subject fit into one of four categories of feeding problems: (a) total refusal, (b) type selectivity, (c) texture selectivity, or (d) type and texture selectivity. Thus, although all 5 subjects exhibited limited intake, the food characteristics correlated with the problem were different for each individual. Results suggest that treatments for limited intake may be based on assessments that show the association of food type or texture to a person's rejection or expulsion of food.     

Measuring behavior in genetic disorders of mental retardation

As researchers have examined the so-called "behavioral phenotypes" of different genetic mental retardation conditions, the measurement of behavior becomes increasingly important. From earlier, more global examinations of noteworthy behaviors or profiles, recent researchers have moved from reliance on a single, all-encompassing questionnaire to more multimethod, multireporter approaches. This paper summarizes strengths and weaknesses in utilizing parent-report questionnaires and checklists; psychiatric nosology and specific psychiatric questionnaires; observational studies; reports from individuals with mental retardation themselves; profile analyses of psychometric test and subtest scores; and "grouping" analyses of items (factor analysis) and people (cluster analysis). Although we advocate a mixture of approaches to behavioral assessment, in future work researchers will require more theoretically driven methods for studying behavior, greater acknowledgment that the child's behavior is simply one event in ongoing interactions-transactions with other people, and more attention to age-related changes in behavioral phenotypes.     

ASSESSMENT AND TREATMENT OF EXCESSIVE STRAIGHTENING AND DESTRUCTIVE BEHAVIOR IN AN ADOLESCENT DIAGNOSED WITH AUTISM

Repetitive behaviors such as excessive straightening are commonly observed among individuals with autism. Attempts to prevent these behaviors may increase the likelihood of other problem behaviors. The present study was designed to assess and treat the excessive straightening and associated destructive behaviors of a 16‐year‐old boy who had been diagnosed with autism and moderate mental retardation. Following a series of functional analyses, an intervention that incorporated functional communication, extinction of destructive behavior, and blocking of repetitive straightening was demonstrated to be effective in reducing straightening and destructive behavior.     

A Better Look at Intelligence

The Planning, Attention, Simultaneous, and Successive (PASS) model is offered as an alternative to the unidimensional conceptualization of intelligence as a general ability. The unidimensional conceptualization has not helped researchers and clinicians understand variations of cognitive functions within special populations such as individuals with learning disabilities, disorders of attention, or mental retardation. Neither has this conceptualization aided in program planning for these individuals. PASS is a model of cognitive function based on contemporary research in both cognition and neuropsychology and provides a theory for both assessment and intervention. This article reviews concepts and examples of PASS theory and its application to reading disabilities and mental retardation. For example, the article links dyslexia with a deficit in successive processing. It also identifies the major difficulties of individuals with Down syndrome in phonological memory and articulation. Further research on successive processing, and planning as it relates to language, is suggested.     

Psychotic manifestations in a patient with mental retardation and a 6.2 megabase deletion at the distal short arm of chromosome 12

Genetic factors are known to contribute to the development of schizophrenia and related psychoses. Cytogenetic abnormalities have been occasionally found in patients with psychotic disorders and, thus, have helped identify candidate gene contributors for these conditions. The individual described here first presented with mental retardation and anxiety disorder in his mid-childhood. In his early 20s, the patient started exhibiting various psychotic manifestations, including delusions and hallucinations. His psychotic symptoms were difficult to control with psychotropic medications. The family history was negative for psychiatric disorders. This patient was found to have a 6.2 megabase deletion of the terminal portion of the short arm of chromosome 12 that was characterized using fluorescence in situ hybridization and microarray comparative genomic hybridization analysis. The maternal chromosomes were normal, but the paternal chromosomes could not be tested. To-date such a chromosomal abnormality has not been described in association with schizophrenia/psychosis. This case suggests that psychosis-associated gene(s) may be located in the terminal region of the short arm of chromosome 12.     

EFFECTS OF REINFORCEMENT FOR ALTERNATIVE BEHAVIOR DURING PUNISHMENT OF SELF-INJURY

A number of variables influence the effectiveness of punishment and may determine the extent to which less intrusive forms of punishment may be used as alternatives to more intrusive interventions. For example, it has been suggested that response suppression during punishment may be facilitated if reinforcement is concurrently available for an alternative response. However, results of basic research demonstrating this finding have not been replicated with interventions more commonly prescribed as treatments for problem behavior. We evaluated the effects of relatively benign punishment procedures (reprimands or brief manual restraint) on the self-injurious behavior of 4 individuals who had been diagnosed with mental retardation, when access to reinforcement for alternative behavior (manipulation of leisure materials) was and was not available. In all cases, punishment produced greater response suppression when reinforcement for an alternative response was available.     

Positron emission tomography methods with potential for increased understanding of mental retardation and developmental disabilities

Positron emission tomography (PET) is a technique that enables imaging of the distribution of radiolabeled tracers designed to track biochemical and molecular processes in the body after intravenous injection or inhalation. New strategies for the use of radiolabeled tracers hold potential for imaging gene expression in the brain during development and following interventions. In addition, PET may be key in identifying the physiological consequences of gene mutations associated with mental retardation. The development of high spatial resolution microPET scanners for imaging of rodents provides a means for longitudinal study of transgenic mouse models of genetic disorders associated with mental retardation. In this review, we describe PET methodology, illustrate how PET can be used to delineate biochemical changes during brain development, and provide examples of how PET has been applied to study brain glucose metabolism in Rett syndrome, serotonin synthesis in autism, and GABAA receptors in Angelman's syndrome and Prader-Willi syndrome. Future application of PET scanning in the study of mental retardation might include measurements of brain protein synthesis in fragile X syndrome and tuberous sclerosis complex, two common conditions associated with mental retardation in which cellular mechanisms involve dysregulation of protein synthesis. Mental retardation results in life-long disability, and application of new PET technologies holds promise for a better understanding of the biological underpinnings of mental retardation, with the potential to uncover new treatment options.     

On the displacement of leisure items by food during multiple-stimulus preference assessments

Previous studies have demonstrated that when food and leisure stimuli are combined in multiple-stimulus preference assessments, individuals typically select food more often, although the leisure stimuli also have known reinforcing properties. The purpose of the current study was to replicate this effect and determine its durability by examining the effect after mealtimes. Four adults who had been diagnosed with severe mental retardation were given three initial multiple-stimulus (without replacement) preference assessments (i.e., food, leisure stimuli, and combined). All participants selected food items as the most preferred stimuli in the combined assessments. Combined assessments were then administered immediately before and after the evening meal for each participant for 1 week. The results showed similar data both before and after mealtimes.     

Short-Term Memory Deficits Are Not Uniform in Down and Williams Syndromes

Neuropsychological investigation of the development of the mnesic function in mental retardation has primarily focused on evaluating short-term memory (STM). Studies have often documented a reduced verbal short-term memory span in individuals with mental retardation and with Down syndrome in particular, compared to groups of mental age-matched controls. However, recent evidence suggests that verbal short-term memory is not equally impaired in all individuals with mental retardation. Findings in children with Williams syndrome are particularly relevant in this regard. Also, data concerning STM for visual information suggest that visual-object and visual-spatial working memory may be differently compromised in people with mental retardation. In particular, individuals with Williams syndrome exhibit specific difficulties in visual-spatial but not in visual-object working memory tasks compared to typically-developing children matched for mental age. Instead, people with Down syndrome show reduced performance in both visual-spatial and visual-object tests. Taken together, these results reinforce the view that intellectual disability is not a unitary condition characterized by homogeneous slowness of cognitive development but a variety of conditions in which some cognitive functions may be more disrupted than others. The finding that the working memory deficit in individuals with Williams and Down syndrome may be qualitatively differentiated also supports the hypothesis that it is not simply a manifestation of general cognitive impairment but, rather, the expression of a specific deficit of a discrete cognitive ability.