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Transcription defects induced by repeat expansion: fragile X syndrome, FRAXE mental retardation, progressive myoclonus epilepsy type 1, and Friedreich ataxia.

Fragile X mental retardation syndrome, FRAXE mental retardation, Progressive myoclonus epilepsy Type I, and Friedreich ataxia are members of a larger group of genetic disorders known as the Repeat Expansion Diseases. Unlike other members of this group, these four disorders all result from a primary defect in the initiation or elongation of transcription. In this review, we discuss current models for the relationship between the expanded repeat and the disease symptoms.

Base Sequence↗

Electroconvulsive therapy and mental retardation.

Reports on use of electroconvulsive therapy (ECT) in persons with mental retardation (MR) and mental illness are meager. We describe the successful use of ECT in the management of medication-resistant mental illness in persons with mental retardation. Details of the treatment of five patients with MR and psychotic disorders are reported. ECT was successful after the failure of adequate trials of traditional pharmacotherapy. Persons with MR did not have disproportionate adverse effects of ECT as a consequence of the MR. Four of the five cases reported received maintenance ECT. ECT should be considered in the affective and psychotic disorders occurring in persons with MR when traditional pharmacotherapy fails.

Adolescent↗

Photographic screening for strabismus among mentally retarded children.

The prevalence of squint among mentally retarded children is much higher than in the general population. A photographic screening method based on the positioning of the 1st and 4th Purkinje image was applied to 80 mentally retarded children. The method was validated against orthoptic examination of the children. Totally 320 exposures were taken. Fourth Purkinje image was visible on 73% of these. Five children were not evaluable from the 4th Purkinje image. The photographic technique was simple and easy to handle, but comparison between the clinical and photographic diagnoses were inconsistent in 12 out of 80 cases, which made the method unreliable. In some cases the clinical assessments also varied from time to time. A combination of clinical orthoptic assessment and the photographic method is suggested.

Adolescent↗

Severe mental retardation in Jordanian children. A retrospective study.

The etiology of severe mental retardation has not previously been studied in Jordan. In a group of 203 mainly severely mentally retarded children born 1975-1985, we found the etiology to be related to two main factors: (1) sequele from high perinatal morbidity or meningitis in infancy leading to a combination of severe mental retardation and cerebral palsy; (2) a high degree of intermarriage and a high frequency of retarded siblings indicating that genetic causes of MR are common. The results underscore the importance of further development of antenatal and perinatal care, especially for poor people and the need of genetic counselling.

Child↗

Efficacy of a pre-retirement planning intervention for aging individuals with mental retardation.

This report describes a study designed to identify variables related to attitudes toward retirement among adults with mental retardation. Seventy-five adults with mild to moderate mental retardation were compared to a group of age peers drawn from the employee population of a regional centre in a Southern American state. It was found that a general satisfaction with life and feelings of preparedness for retirement were strongly related to attitudes toward retirement among both groups. Other common correlates that were significantly related among both groups included financial preparedness, health perceptions, orientation to work and commitment to work. Also observed was a high correlation between life satisfaction and orientation to work and commitment to work among both groups. The authors also found that pre-retirement planning did prove to be a generally effective means of teaching older adults with mental retardation the options that are available during their retirement years, but did not seem to change their attitudes toward retirement or life satisfaction. The authors conclude that retirement has positive connotations for most individuals with mental retardation, particularly if they feel that they are prepared for it.

Adaptation, Psychological↗

Interpersonal tactics and communicative strategies of Anglo-American and Mexican-American mildly mentally retarded and nonretarded students.

In this investigation, we compared the preferred interpersonal tactics of mildly mentally retarded Mexican-American and Anglo-American children in an experimental social problem-solving situation. Sixty subjects were divided into four equal groups based upon ethnicity (Mexican-American or Anglo-American) and educational status (mildly mentally retarded or nonretarded). Results indicated that although there were no ethnic group differences, differences in preferred problem solving strategies were demonstrated by mentally retarded and nonretarded children. Overall, nonretarded children tended to utilize strategies such as cooperation and temporary withdrawal more often than mentally retarded children.

Child↗

Primary cutis verticis gyrata or pachydermia verticis gyrata: a peculiar scalp disorder of mentally retarded adult males.

BACKGROUND: Primary or idiopathic cutis verticis gyrata (CVG) is often associated with mental retardation or chronic schizophrenia. OBJECTIVE: The aim of the present study was to evaluate the prevalence of primary CVG and its histological aspects in a psychiatric adult population. METHODS: Eighty-three hospitalized psychiatric adult patients were examined for the primary form of CVG. Forty-nine (44 males and 5 females) out of them were schizophrenic, 16 (14 males and 2 females) were mentally retarded and the remaining 18 were affected by different psychiatric disorders. RESULTS: Three males, 2 mentally retarded and 1 schizophrenic, were found to be affected and the clinical diagnosis was confirmed histologically. CONCLUSION: The high prevalence of primary CVG in males with mental retardation might be explained by ethnic factors or by the use of an adequate diagnostic methodology, improved by shaving the scalp hair in patients suspected to be affected. The term pachydermia verticis gyrata is suggested for the primary CVG, which is the most common scalp disorder in such a population.

Adult↗

Chronological age and performance of persons with mental retardation on verbal subtests of the Wechsler Intelligence Scale for Children--Revised, French Version.

The Influence of chronological age on verbal intelligence of persons with metal retardation was studied using the French version of the Wechsler Intelligence Scale for Children--Revised. Participants were 1,101 children and adolescents divided into two groups according to the severity of metal retardation. The first group included 551 participants with moderate mental retardation, the second 550 participants with mild mental retardation. Analyses indicated a significant association between chronological age and raw scores on the four Verbal Comprehension subtests, even with performance on Perceptual Organization and Freedom from Distractibility subtests held constant. This finding suggests the relationship between chronological age and verbal intelligence is valid for persons with moderate mental retardation as well as for those with mild metal retardation.

Adolescent↗

A gene for nonsyndromic X-linked mental retardation (MRX77) maps to Xq12-Xq21.33.

Nonsyndromic X-linked mental retardation (MRX) is a highly heterogeneous condition in which mental retardation appears to be the only consistent manifestation. According to the most recent data, 77 MRX families with a lod score of >2 have been mapped and eight genes have been cloned. We hereby report on a linkage analysis performed on a Greek family with apparently nonsyndromic MRX. The affected males have moderate to severe mental retardation, severe speech problems, and aggressive behavior. Two-point linkage analysis with 26 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 27 Mb interval in Xq12-Xq21.33. The maximum LOD score was found for markers DXS1225, DXS8114, and DXS990 at 2.36, 2.06, 2.06, respectively at theta = 0.00. Recombination was observed for DXS983 at the proximal side and DXS6799 at the distal side. Nineteen other MRX families have been described with a partial overlapping disease gene interval in proximal Xq. No mutations were found in the MRX77 family for three known or candidate MRX genes, from this region OPHN1, RSK4, and ATR-X. These data indicate that the Xq12-Xq21.33 interval contains at least one additional MRX gene.

Chromosome Mapping↗

What individual, provider, and community characteristics predict employment of individuals with mental retardation?

Characteristics influencing employment of individuals with mental retardation were analyzed to evaluate employment rates for county providers. Participants in the sample (N = 11,743) earned at least $50 per week for a 6-month period. Good physical and emotional health, being male, age between 18 and 49, IQ between 50 and 75, and good adaptive skills were associated with employment. Eighteen percent of the variability in employment rates was explained by the ratio of individuals served by the Boards to the county population and the percentage of the county population living in rural settings. Median income, unemployment rates, and poverty explained 22% of the variance in noncompetitive employment rates. Results suggest that health promotion programs could help individuals with mental retardation obtain and sustain employment.

Adolescent↗

Social work services for elderly persons with mental retardation: a case example.

Elderly persons with mental retardation constitute a relatively small and often overlooked subgroup of our aged population. As their numbers continue to grow, it is likely that social workers in health care and social service agencies serving either the mentally retarded or the aged will increasingly encounter such older persons as clients. This paper presents a case study that illustrates some of the problems and issues that social workers in a variety of community-based and institutional-based agencies are likely to face in helping to provide for the health and residential care needs of members of this group.

Activities of Daily Living↗

Familial mental retardation: a continuing dilemma.

The heterogeneous nature of mental retardation, as well as certain common practices of workers in the area, has resulted in a variety of conceptual am biguities. Considerable order could be brought to the area if, instead of viewing all retardates as a homogeneous group arbitrarily defined by some I.Q. score, workers would clearly distinguish between the group of retardates known to suffer from some organic defect and the larger group of retardates referred to as familial retardates. It is the etiology of familial retardation that currently constitutes the greatest mystery. A number of authorities have emphasized the need for employing recent polygenic models of inheritance in an effort to understand the familial retardate. While appreciating the importance of environment in affecting the distribution determined by genetic inheritance, these workers have argued that familial retardates are not essentially different from individuals of greater intellect, but represent, rather, the lower portion of the intellectual curve which reflects normal intellectual variability. As emphasized by the two-group approach, retardates with known physiological or organic defect are viewed as presenting a quite different etiological problem. The familial retardate, on the other hand, is seen as a perfectly normal expression of the population gene pool, of slower and more limited intellectual development than the individual of average intellect. This view generates the proposition that retardates and normals at the same general cognitive level-that is, of the same mental age-are similar in respect to their cognitive functioning. However, such a proposition runs headlong into findings that retardates and normals of the same mental age often differ in performance. Such findings have bolstered what is currently the most popular theoretical approach to retarded functioning-namely, the view that all retardates suffer from some specific defect which inheres in mental retardation and thus makes the retardate immutably "different" from normals, even when the general level of intellectual development is controlled. While these defect or difference approaches, as exemplified in the work of Luria, Spitz, Ellis, and Lewin and Kounin, dominate the area of mental retardation, the indirect, and therefore equivocal, nature of the evidence of these workers has generated considerable controversy. In contrast to this approach, the general developmental position has emphasized systematic evaluation of the role of experiential, motivational, and personality factors. As a central thesis, this position asserts that performance on experimental and real-life tasks is never the single inexorable product of the retardate's cognitive structure but, rather, reflects a wide variety of relatively nonintellective factors which greatly influence the general adequacy of performance. Thus, many of the reported behavioral differences between normals and retardates of the same mental age are seen as products of motivational and experiential differences between these groups, rather than as the result of any inherent cognitive deficiency in the retardates. Factors thought to be of particular importance in the behavior of the retardate are social deprivation and the positive- and negative-reaction tendencies to which such deprivation gives rise; the high number of failure experiences and the particular approach to problem-solving which they generate; and atypical reinforcer hierarchies. There is little question that we are witnessing a productive, exciting, and perhaps inevitably chaotic period in the history of man's concern with the problem of mental retardation. Even the disagreements that presently exist must be considered rather healthy phenomena. These disagreements will unquestionably generate new knowledge which, in the hands of practitioners, may become the vehicle through which the performance of children, regardless of intellectual level, may be improved.

Humans↗

Living circumstances of children and adults with mental retardation or developmental disabilities in the United States, Canada, England and Wales, and Australia.

The purpose of this article was to collate evidence to describe where people with mental retardation or developmental disabilities live in five developed countries: United States, Canada, England, Wales, and Australia. Family homes are important dwelling places for people with mental retardation. They are the home of the great majority of children with mental retardation and a considerable proportion of adults with mental retardation. The likelihood of placement outside the family home increases with adulthood and progressively as people age. Adults with mental retardation live in a wide variety of settings, with formal residential provision frequently dependent on the arrangements that the authorities responsible for providing service support have chosen to make. There has been a considerable move away from accommodating people in large segregated and geographically isolated institutions in the countries considered. However, the current range of accommodation includes much with a distinctively different character to the homes where other citizens live. Many people still live in larger groups than would be ordinarily found in typical homes and this may necessitate departure from the architectural norm. In all of the countries considered, there has been a recent trend towards small community settings, compatible with typical housing architecture. This appears furthest advanced in the U.S. but is discernible elsewhere. Availability of residential services at a national level varies between 100 and 155 places per 100,000 total population. Regional variation within countries is even greater. In no case is the national availability considered adequate to meet the demand arising from changing need or expectations. MRDD Research Reviews 7:115-121, 2001. (c) 2001 Wiley-Liss, Inc.

Adult↗

Observations of the role relations and behavior between older children with mental retardation and their younger siblings.

Children with mental retardation and their younger siblings without retardation were observed interacting in three naturally occurring in-home contexts (toy play, television viewing, and snack). Comparison siblings without retardation who were matched on age, sex, race, parental marital status, education, and family income were also observed. Interactions between children with retardation and their siblings were characterized by accentuated role asymmetries that favored the younger siblings, whereas the older siblings were dominant in the comparison group. No differences in affect were found between the sibling groups. The competence of the child with mental retardation reliably predicted sibling role asymmetries, and the observational contexts influenced sibling behavior in both groups. Gender differences in roles and behavior were minimal.

Activities of Daily Living↗

Sixty years of X-linked mental retardation: a historical footnote.

X-linked mental retardation (XLMR) is a most exciting field of modern medical genetics. It made spectacular advances over the last twenty years, after the advent of molecular genetics. The discovery of the FMR1 gene unraveled the cause of the most common form of heritable mental retardation and provided the prototype of dynamic mutations. New genes continue to be mapped to the X chromosome and more and more are being cloned and characterized, clarifying the nosology of XLMR and, more importantly, adding to our understanding of the mechanisms of intellectual development, normal and abnormal. Looking back to a more or less recent past may provide clues for future discoveries.

Chromosome Mapping↗

Attitudes of parents of mentally retarded children toward normalization activities.

Parents of mentally retarded children were surveyed via a 5-point Likert scale to determine their attitudes toward normalization in general and in relation to their child. Results indicated significant differences in response, with the more positive attitudes being those associated with a general (the mentally retarded population) rather than specific (my child) referent. Within the general-referent group, parents of TMR children displayed the most positive attitudes. Age, sex, and level of retardation had no effect on child-specific responses.

Adolescent↗

X-linked mental retardation (XLMR): from clinical conditions to cloned genes.

X-linked mental retardation (XLMR) is a heterogenous set of conditions responsible for a large proportion of inherited mental retardation. Approximately 200 XLMR conditions and 45 cloned genes are now listed in our catalogue on the Internet at http://xlmr.interfree.it/home.htm. Traditionally, XLMR conditions were subdivided into specific (MRXS) and nonspecific (MRX) forms, depending on their clinical presentation. Now that a growing number of candidate genes have become available for screening XLMR families and patients, this distinction is becoming less useful and similar conditions that had been previously listed as separate can now be grouped together because different mutations in the same gene have been identified. Furthermore, different mutations in the same XLMR gene may account for diseases of increasing severity, but can also cause different phenotypes. As the functions of proteins corresponding to these genes are characterized, biological networks involved in causing mental retardation and conversely in supporting normal intellectual functioning will be discovered. Molecular biologists and neurobiologists will need to cooperate in order to verify the effects of XLMR gene mutations in the context of neuronal circuitry. Eventually, DNA and protein microarray technologies will assist researchers and physicians in reaching a diagnosis even in small families or in individual patients with XLMR.

Cloning, Molecular↗

The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2.

Fragile X Mental Retardation Syndrome is the most common form of hereditary mental retardation, and is caused by defects in the FMR1 gene. FMR1 is an RNA-binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. The specific function of FMR1 is not known. As a step towards understanding the function of FMR1 we searched for proteins that interact with it in vivo. We have cloned and sequenced a protein that interacts tightly with FMR1 in vivo and in vitro. This novel protein, FXR2, is very similar to FMR1 (60% identity). FXR2 encodes a 74 kDa protein which, like FMR1, contains two KH domains, has the capacity to bind RNA and is localized to the cytoplasm. The FXR2 gene is located on human chromosome 17 at 17p13.1. In addition, FMR1 and FXR2 interact tightly with the recently described autosomal homolog FXR1. Each of these three proteins is capable of forming heteromers with the others, and each can also form homomers. FXR1 and FXR2 are thus likely to play important roles in the function of FMR1 and in the pathogenesis of the Fragile X Mental Retardation Syndrome.

Amino Acid Sequence↗