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PubMed1995

Syndromal mental retardation due to mutations in a regulator of gene expression.

Mental handicap is a common clinical problem that has been a relatively neglected area of research. Though the causes are varied and complex, molecular biologists are making progress in understanding the mechanisms in some cases, particularly where there are distinguishing phenotypic or genetic markers. The fortuitous association of alpha thalassaemia with a form of mental retardation has allowed us to define a specific X-linked syndrome (ATR-X). Positional cloning was used to define a disease interval and examination of candidate genes demonstrated that mutations in a gene, XH2, showing homology to the SNF2 superfamily were responsible for this syndrome. The complex ATR-X phenotype suggests that this gene, when mutated, down-regulates the expression of several genes including the alpha-globin genes indicating that it could be a global transcriptional regulator. It is conceivable that this mechanism is involved in other forms of syndromal mental retardation.

Child↗
PubMed2001

Subcellular localization of fragile X mental retardation protein with the I304N mutation in the RNA-binding domain in cultured hippocampal neurons.

1. Fragile X syndrome, the most common form of inherited mental retardation, is caused by the lack or dysfunction of fragile X mental retardation protein (FMRP). The 1304N mutation in the RNA-binding domain of FMRP results in an exceptionally severe form of mental retardation. 2. We have investigated the subcellular localization of FMRP and its 1304N-mutated form in cultured hippocampal neurons and PC12 cells, using immunofluorescence microscopy. In PC12 cells, FMRP was predominantly localized to the cytoplasm and also to the processes after differentiation by NGF. 3. In cultured hippocampal neurons, granular labeling was detected along the neuronal processes. 4. Double-labeling with synaptophysin antibody revealed FMRP at synaptic sites in neurons. 5. The 1304N mutation did not appear to affect the transport of FMRP to dendrites or its localization at synaptic sites. Thus, FMRP is a synaptic protein and the severe phenotype observed in the patient with the 1304N mutation is not produced by alterations in dendritic transport.

Animals↗
PubMed1987

Mild mental retardation in northern Finland.

The occurrence and aetiology of mild mental retardation (IQ 50-70) and borderline retardation (IQ 71-85) were studied on the basis of a one-year (1966) birth cohort of 12,058 live-born infants, which were followed prospectively up to the age of 14 years. The cumulative incidences for MMR and borderline retardation were 5.5 and 13.4 per 1,000 respectively. In the borderline group there was a male preponderance of 2.3:1 as compared to 1.2:1 in MMR children. A causal factor could be identified for 46.9% of MMR children and 31.4% of borderline ones. Prenatal factors had very little bearing, since only 6% of the MMR and 6.7% of the borderline cases had such, as compared to 28.7% and 20.4% for perinatal factors and 12.1% and 4.3% for postnatal factors. An analysis of the impact of specific obstetrical and perinatal factors revealed that very few constituted relevant relative risks for mental retardation.

Adolescent↗
PubMed1986

[Behavior disorders in children with mental retardation (data of an epidemiologic study)].

An epidemiological examination of mentally retarded children aged 8-14 years revealed behavioural deviations hindering the patients' adaptation in 31.8%. Behavioural disorders were due to the psychopathy-like syndrome of organic genesis in one group of patients and psychogenic pathological formation of the personality in another. Apart from this, hyperdynamic syndrome (other than psychopathy-like) and neurosis-like disturbances were also attended by behavioural disorders. Among children who had been left without parents from early childhood behavioural difficulties were observed two times more frequently than among children brought up in families, including the so-called difficult families. A total of 66% of mentally-retarded children were either once or repeatedly hospitalized in psychiatric institutions, mainly, in connection with an insufficient correction of behavioural deviations at auxiliary and boarding schools.

Adolescent↗
PubMed1990

Dementia and depression in elders with mental retardation: a pilot study.

A preliminary investigation of cognitive decline and depressive symptomatology is presented with older adults who have mental retardation. A series of different assessment instruments are reviewed and tested in a pilot study. A review of dementia and depression with respect to elders with mental retardation is presented to place the study in perspective. Findings reveal decreasing cognitive ability is associated with higher rates of observed depression and reported behavioral problems. Trends suggested those more elderly displayed more depressive behaviors, psychotropic medication was a common treatment, and cognitive decline was associated with lower initial intellectual levels. Dementia and depression is a complicated symptom complex to identify in aging adults with mental retardation.

Activities of Daily Living↗
PubMed1990

[The mentally retarded in the local community--living conditions, family situation, school attendance, work, leisure and aid activities].

The Norwegian Government has decided to reform the care of the mentally retarded by closing the institutions and by placing the whole responsibility for all mentally retarded with the local authorities. The idea is to integrate the mentally retarded into the community in order to normalize their living conditions. A survey on the demand for housing, work, schooling, leisure activities and home support was carried out in order to establish the consequences of the reform. 3/4 of the whole group are adults, and both the group now living at home and the group in institutions will need new housing, either individually or in small groups. The same groups will have to be offered specially adopted work. Several have never attended school or at most have very incomplete schooling compared with what the law prescribes. Offers of leisure activities and home support will have to be expanded by three or four times the present level. An important finding was that the group who lived at home were in greatest need of the care and activities for which the local authorities will be responsible. They have very old parents and for many of them the situation will soon become critical. The reform will have large economic consequences, and the Government is willing to pay only a part of these costs.

Adult↗
PubMed1996

Families of adults with mental retardation: stress levels and need for services.

The study described in this article sought to determine whether stress experienced by families of adults with mental retardation was a function of characteristics of caregivers or care recipients, support service needs, and needs for personal care and supervision. Data from interviews with 105 families indicated that the marital status of the caregiver; the level of retardation, frequency of maladaptive behaviors, and health status of the adult family member with mental retardation; and the number and level of services needed were factors in the stress experienced by families. This examination of how perceived stress and needs for services interact provides information essential to developing and funding effective supports to families caring for adults with mental retardation and other developmental disorders.

Adult↗
PubMed1981

A review of training programs for providers of foster family care to mentally retarded persons.

The training needs of foster care providers serving mentally retarded persons have been acknowledged for some time. This review of specific training programs demonstrates that a variety of excellent materials and strategies for meeting these needs are now available. A number of important tasks remain. First, existing training programs need to be implemented more widely. Second, new programs and training materials need to be developed to address needs not adequately met by existing programs. Finally, there is a need to conduct systematic evaluations of care provider training on a more regular basis. The results of these evaluations must then be used to guide refinements in future training efforts. This is an essential step if these programs are to be effective in meeting their goal of improving the quality of care offered to mentally retarded persons by foster family care providers.

Education↗
PubMed1984

A true experiment evaluating adult skill training for severely mentally retarded secondary students.

Skill acquisition by secondary-level severely mentally retarded students was assessed on functional community and living skills task analyses. Students were trained in natural settings according to a behavioral analysis of the curriculum into systematic teaching and error-correction procedures. Classroom training in the district high school supported the teaching that occurred in the community. The evaluation of student performance on specific skills was done using random assignment to training and control conditions in a cross-over design. Students showed significantly greater gains on those tasks for which they were trained than on those for which they were not. In addition to this specific skill training, a daily checklist showed significant progress by all students on a broad array of skill sequences. Discussion stressed the contribution of the project to ideologically appropriate public school programs for severely mentally retarded students, to behaviorally based instructional technology, and to evaluation using true experimental designs.

Activities of Daily Living↗
PubMed1993

Span of apprehension in mentally retarded children: an initial investigation.

The present investigation is the first to apply Estes' (1965) span of apprehension task to the study of attentional functioning in mentally retarded persons. Detection accuracies of 25 children diagnosed as mildly mentally retarded and 25 non-retarded children were compared under conditions of 100-ms exposure duration, and either two, four, six or eight distractor letters. Significant main effects of subject group and distractor number were found, with no interaction. These results provide converging evidence in support of previous positions that posit a structural deficit in mentally retarded individuals with respect to centrally mediated processing.

Attention↗
PubMed2001

Characterization of ARHGEF6, a guanine nucleotide exchange factor for Rho GTPases and a candidate gene for X-linked mental retardation: mutation screening in Börjeson-Forssman-Lehmann syndrome and MRX27.

Börjeson-Forssman-Lehmann syndrome (BFLS) is a syndromic X-linked mental retardation that has been mapped by linkage to Xq26-q27. A nonsyndromic mental retardation family, MRX27, has also been localized to a region of the X chromosome overlapping Xq26-q27. The gene for ARHGEF6 (also known as alphaPIX or Cool-2), a newly identified guanine nucleotide exchange factor, was identified as a potential candidate XLMR gene, due to its location within the BFLS and MRX27 critical regions and its function in the regulation of PAK3 (a known MRX gene). The full coding sequence and genomic structure of the gene for ARHGEF6 was established in silico, based on available genomic, EST, and cDNA sequence information. Mutation analysis in BFLS- and MRX27-affected individuals was carried out. No mutations were found in two BFLS families or MRX27. Although ARHGEF6 is unlikely to be the gene responsible for either BFLS or MRX27, it remains a prime candidate for nonspecific or syndromic mental retardation linked to Xq26.

Alternative Splicing↗
PubMed1982

Concurrent occurrence of rapid eye movement with spindle burst during nocturnal sleep in mentally retarded children.

Concurrence of REM and sleep spindle in 45 mentally retarded children (from 4 months to 8 years of age) was studied throughout nocturnal sleep, and the following results were obtained. (1) Twenty-five cases showed a single or burst of REMs during stage NREM with sleep spindles. (2) Twenty-nine cases showed sleep spindles at the beginning or toward the end of stage REM sleep. (3) No significant difference in DQ was found between the subjects with and without REMs during stage NREM sleep. The former subjects, however, had more normal clinical EEGs than the latter. (4) No significant difference in DQ or clinical EEG classification was revealed between the subjects with REMs during stage NREM sleep and those with spindles during stage REM sleep. (5) It was concluded that the concurrence of REM and sleep spindle during stage NREM is a useful sign for early diagnosis of mental retardation.

Child↗
PubMedDate not supplied

Oral ketamine facilitates induction in a combative mentally retarded patient.

Induction of general anesthesia in the agitated or combative mentally retarded patient is challenging. Oral ketamine facilitated the smooth and safe induction of anesthesia in an adult mentally retarded patient with a history of violent behavior toward health care providers. The oral administration of ketamine is an effective alternative induction technique in situations where the intravenous (IV), intramuscular (IM), or inhalation approach may be difficult or hazardous.

Administration, Oral↗
PubMed1976

Low lead levels and mental retardation.

Borderline and mildly retarded children attending the hospital developmental evaluation clinic were divided into two groups on the basis of the presence or absence of a pred with a paediatric control group using blood-lead concentration as the independent variable. Children with a history of diagnosed lead posisoning were excluded from the study. The group of mentally retarded children "aetiology unknown" had statistically significantly raised blood-lead concentrations but the mentally retarded sample with "probable aetiology" showed no significant difference in lead concentrations from those of the normal controls. It is concluded that the association between lead and mental retardation extends over a much wider range than hitherto suspected and that the nature of this association is independent of a history of "encephalopathic" lead poisoning. It is suggested that physicians should consider raised lead levels in their examination of all children suspected of mental retardation and that the numerical definition of lead toxicity should be re-evaluated.

Child↗
PubMed1981

Can nutritional supplements help mentally retarded children? an exploratory study.

To explore the hypothesis that mental retardations are in part genetotrophic diseases (diseases in which the genetic pattern of the afflicted individual requires an augmented supply of one or more nutrients such that when these nutrients are adequately supplied the disease is ameliorated), we carried out a partially double-blind experiment with 16 retarded children (initial IQs, approximately 17-70) of school age who wee given nutritional supplements or placebos during a period of 8 months. The supplement contained 8 minerals in moderate amounts and 11 vitamins, mostly in relatively large amounts. During the first 4- month period (double-blind) the 5 children who received supplements increased their average IQ by 5.0-9.6, depending on the investigator, whereas the 11 subjects given placebos showed negligible change. The difference between these two groups is statistically significant (P less than 0.05). During the second period, the subjects who had been given placebos in the first study received supplements; they showed an average IQ increase of at least 10.2, a highly significant gain (P less than 0.001). Three of the five subjects who were given supplements for both periods showed additional IQ gains during the second 4 months. Three of four children with Down syndrome gained between 10 and 25 units in IQ and also showed physical changes toward normal. Other evidence suggests that the supplement improved visual acuity in two children and increased growth rates. These results support the hypothesis that mental retardations are in part genetotrophic in origin.

Adolescent↗
PubMed2000

Sensory stimulation increases cortical expression of the fragile X mental retardation protein in vivo.

Fragile X syndrome is a common cause of mental retardation that results from the absence of the fragile X mental retardation protein (FMRP), an RNA binding protein whose function remains unclear. Recent in vitro work has demonstrated that the protein is translated near the synapse in an activity dependent manner [33]. We therefore asked whether expression of FMRP might be altered by neuronal activity in vivo. Using immunoblots of different sub-cellular fractions of the rat somatosensory cortex, we show that the levels of FMRP increase significantly following unilateral whisker stimulation, a model of experience dependent plasticity. This increase is greatest between 2 and 8 h after the stimulus and is seen in both a synaptosomal fraction as well as a sub-cellular fraction enriched for polyribosomal complexes. In contrast, detectable levels of FMRP within the somatosensory cortex show either a decrease or no change after a kainic acid induced seizure compared to water treated controls. Our findings demonstrate that FMRP expression levels are modulated in vivo in response to neuronal activity and suggest a role for FMRP in activity dependent plasticity.

Animals↗
PubMed1993

New X-linked syndrome with severe mental retardation, severely impaired vision, severe hearing defect, epileptic seizures, spasticity, restricted joint mobility, and early death.

A family with an X-linked mental retardation syndrome involving seven children in two generations is reported. The syndrome includes microcephaly, severe mental retardation, optic atrophy with severely impaired vision or blindness, a severe hearing defect, spasticity, epileptic seizures, restricted movement of the large joints, and death in infancy or early childhood. We conclude that this is a distinct, previously unrecognized X-linked mental retardation syndrome.

Abnormalities, Multiple↗