A mere glance at a family photograph of the Victorian era leaves little doubt of the position of the figure exuding impervious, authoritarian detachment. Austere, rigid and solemn, it is not hard to guess who cast the shadow over the picture. Arrestingly imposing in his role as backbone of the family, this is the nineteenth century legacy image of the father. However, the last century has seen fatherhood redefine itself and the more liberal, lenient and openly loving figure replaced the strict patriarchal model. In contemporary times, fathers are regularly seen comfortably behind a stroller, outdoors with children on their shoulders, at home tousling with their children, and considerably more involved in school and social events. Unashamedly, fathers have moved toward both acknowledging and displaying a softer paternal image. By definition fatherhood is a decidedly individual concept and a unique experience, involving much more than being the male parent in a family, the family protector, or the provider of paycheques. Although the past decade has seen a surge of research and interest in fatherhood with an increased recognition that the involvement of fathers contribute to the well-being, cognitive growth and social competence of their children, there remains a deficit in research on the experiences, perceptions and involvement of fathers of children diagnosed with Down syndrome. And whilst most of this knowledge base is extrapolated from studies about the mother’s experience, true understanding requires that fathers are studied directly. Mothers and fathers respond differently to the pressure associated with raising a child with Down syndrome and literature supports the common view that men are less likely and easy to engage in therapy than women, are less likely to attend therapy, or seek help for physical or psychological problems. For fathers of any differently abled child, the distance between the idealized fathering experience and the actual one may be enormous. Based upon the patriarchy model of the family, in many conventional homes, the wife and mother is like a thermometer, sensing and reflecting the home’s temperature, whilst the father and husband is like the home’s thermostat, which determines and regulates the temperature. The equilibrium of the father plays an important role in his ‘thermostat settings’ to set the right temperature in the marriage and his family. Having a differently abled child is almost never expected and often necessitates a change in plans as the family members adjust their views of their own future, their future with their child, as well as how they will henceforth operate as a family.Some fathers may experience uncertainty about their parenting role of a child diagnosed with Down syndrome, often resulting in peculiar behaviours of the father. This may include engrossing themselves into their work, hobbies, sport, and so forth, almost abdicating their duty as father; believing that the mother knows best (sometimes using their own lack of knowledge as a cop-out); or, they simply withdraw because the mother takes such complete control of every aspect of the child that the father feels inadequate, superfluous, and peripheral as parent. Each parent grieves the ‘loss’ of the child they expected in their own individual way. However, such a highly emotive situation may be compounded by the following aspects: the undeniable pressure of caring for the differently abled child; the additional financial burden; a waning social life; and, the incapacity to cope emotionally whilst invariably displaying the contrary purely to create the illusion that they are indeed coping. Fathers need to develop strategies and skills to cope with the very real and practical needs of parenting their child with Down syndrome, to furthermore minimize relationship conflict and misunderstanding, and to support their child’s optimal development. How these specific issues are embraced and managed may dramatically influence the peace and harmony of family life as well as the marital relationship. This study explores the perspectives of fathers of a child with Down syndrome to ultimately support this unique journey as they navigate their way through “Down”town Holland, as illustrated in the analogy to follow.

This thesis deals with opportunities of mentally disabled people in society. First of all it is defined the term mental retardation, its degree and causes. The following describes the education and upbringing of mentally handicapped. The thesis also discusses approaches to work with mentally disabled people. Another section deals with supported employment. The aim of this thesis is to determine the possibilities of mentally disabled people in society.

The aim of this study is to establish the impact of mental retardation on family functioning. The researcher conducted the research in the Waterberg district of the Limpopo province. The lack of insight on the part of the family on how to cope with such circumstances motivated the researcher to conduct the study. Most families do not have the experience of caring for a mentally handicapped member and therefore need information and support on how to cope with the condition. The study is qualitative and exploratory in nature. The research question was; “What is the impact of mental retardation on family functioning”? A simple random sampling was used in the study. The sample was selected from all the registered children attending three different day- care centres in the Waterberg district for the past three months prior the investigation. Ten parents (one per household) of children with mental retardation were interviewed using a semi structured interview schedule. A phenomenological design was used and participants’ experiences of family life and reactions to the realization that they have a child with mental retardation are discussed. Data consisted of audio taped and written interviews. The data collected was transcribed and analyzed according to qualitative methods. The research findings show that mental retardation has an impact on family functioning. Families had to make new adjustments to accommodate the child and his/her special needs. The researcher recommends that service providers should receive training on issues related to mental retardation so as to provide the much needed services to these families. It was found that the burden of caring, financial constraints, lack of community support, the manner in which the disclosure was handled and the lack of services, all had a negative impact on the family. / Dissertation (MA(Social Work))--University of Pretoria, 2008. / Social Work and Criminology / unrestricted

The mechanisms that govern the repression of 5-HT1A receptor gene expression mediated by a novel mental retardation gene, Freud-1, were examined in HEK293 and SKNSH cells. This study provides a possible mechanism of 5-HT1A receptor gene regulation by Freud-1, which, to mediate its action, recruits Swi/Snf and Sin3A/histone deacetylase (HDAC) complexes in non-neuronal HEK293 cells and Swi/Snf only in neuronal, 5-HT1A receptor-expressing SKNSH cells. Thus, Freud-1 has a dual mechanism of repression depending on cell type: HDAC dependent in HEK293 cells and HDAC independent in SKNSH cells. In addition, I present evidence that Freud-1 is not sumoylated at its consensus sumoylation sites and I present the lipid binding properties of Freud-1 and Freud-1 mutants.

An excess of males among the mentally retarded has been noted in practically all surveys of a mentally retarded population. It has been hypothesized that X-linked genes may account for this excess. The main purpose of this study was to test the hypothesis using data on the mentally retarded in British Columbia. A second purpose was to calculate the frequency of non-specific X-linked mental retardation in the population. In addition, an attempt was made to delineate clinical types of X-linked mental retardation. Data on the mentally retarded in British Columbia were obtained from the B.C. Health Surveillance Registry. The Registry also provided information on sibships with two or more sibs affected with non-specific mental retardation. Family histories on sibships with two or more affected males were obtained from the Department of Medical Genetics, institutions for the mentally retarded, namely Woodlands School and Tranquille, and in some cases personal interviews. The number of mothers in British Columbia giving birth to two or more sons in a defined birth cohort was retrieved from the linked family records of the B.C. Record Linkage Project. Families with a pattern of X-linked inheritance for non-specific mental retardation were ascertained while family histories on sibships with two or more affected males were being recorded and by reviewing files of other non-specific mentally retarded males in the Department of Medical Genetics, Woodlands School and Tranquille. Clinical and psychological characteristics of the mental retardation in males from these families were obtained from medical files from the same sources. Among the mentally retarded in British Columbia, there is an overall 28.2% excess of males. The extent of this excess is similar to that observed in other studies. This excess of males is seen at all levels of retardation except at the profound level. Mental retardation of known causes does not significantly contribute to the excess, which is due primarily to nonspecific mental retardation. Non-specific mental retardation in two or more sibs may be genetic in origin. Data from sibships with both males and females affected do not support an hypothesis of multifactorial inheritance with specific sex thresholds accounting for the excess of mentally retarded males. A ratio of 3.1:1 of sibships with two or more affected males to sibships with two or more affected females suggests that X-linked inheritance may account for the excess of male affected sibships. Family history data on sibships with two or more affected males provide evidence that X-linked genes can account for the excess of male affected sibships. A minimum frequency of 1.83 per 1,000 males for X-linked mental retardation in the population of British Columbia was calculated using sibship data. This frequency can account for the entire excess of non-specific mentally retarded males in the province. Mental retardation inherited in an X-linked pattern may be due to either single genes on the X chromosome or autosomal dominant genes with sex-limited expression. Distinguishing between the two types of genes was not possible in the present study. Specific clinical subtypes of X-linked mental retardation could not be differentiated due to a large amount of variability which was found not only in the level of retardation but also in associated psychological, neurological and physical characteristics. Although further clinical, biochemical and cytogenetic investigations of affected males in families with X-linked mental retardation may elucidate subtypes of non-specific mental retardation, variabiliy in phenotypic expression has been identified as an important feature of X-linked mental retardation. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

A form of familial sex-linked mental retardation has been associated with the expression of a fragile site near the terminal end of the long arm of the X chromosome. Previous reports on the fragile X chromosome showed expression of the fragile site to be limited to chromosome preparations from peripheral blood lymphocytes of mentally retarded males and their female relatives in families in which the disorder was segregating. Fragile site expression has also been shown to be a function of the medium employed in cell culture. The fragile X chromosome could only be demonstrated in lymphocytes cultured in medium 199 or media deprived of folic acid. This study was undertaken to develop a method for demonstrating the fragile X chromosome in cultured skin fibroblasts. Fibroblast cell lines from five patients (two mentally retarded males, two obligate carrier females, and a potential carrier female) from a family in which familial sex-linked mental retardation was known to be segregating were established and routinely maintained in a complete culture medium. Forty-three hours prior to chromosome harvest, cells from each patient were transferred to media deficient in folic acid. Under conditions of folic acid deprivation, it was possible to elicit expression of the fragile X chromosome in skin fibroblasts from all five patients studied. No fragile X chromosomes were detected in fibroblasts from three normal control subjects. In a preliminary assessment of the reliability of the fibroblast method, three patients (two mentally retarded males and a potential carrier female) from a second unrelated family in which the disorder is known to be segregating were studied with this method. The fragile X chromosome could be demonstrated in fibroblasts from both of the retarded male patients but could not be. demonstrated in fibroblast chromosome preparations from the potential carrier female. Lymphocytes for all patients studied were grown under similar folate deprived conditions for the purpose of comparing the effectiveness of fibroblast culture with lymphocyte culture in demonstrating the expression of the fragile X chromosome. Neither tissue was shown to consistently provide a higher frequency of expression of the fragile X chromosome. In addition to folate deprivation, it was shown that two other features of the fibroblast method influenced the frequency of expression of the fragile X chromosome. The fragile site was expressed at a significantly higher frequency in chromosome preparations in which the chromosomes were not severely contracted. The frequency of expression in fibroblasts was also shown to be significantly higher with a hypotonic treatment at chromosome harvest using 1% NaCitrate rather than 0.075M KC1. Because fragile site expression was shown to be a function of the degree of chromosome condensation, two agents, 5-BrdU and actinomycin-D, were studied to examine their decondensation effects on the frequency of expression. Neither BrdU nor actinomycin D proved effective in accentuating the frequency of expression. Since fibroblasts behave much like amniocytes in terms of cell culture and chromosome harvest, the development of a method for demonstrating the fragile X chromosome in cultured skin fibroblasts is a step toward the prospect of reliable antenatal diagnosis of familial sex-linked mental retardation associated with a fragile X chromosome. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Os objetivos deste estudo foram estimar a prevalência da deficiência intelectual aos 7-8 anos de idade em uma coorte de nascimentos, através de investigação genética clínica e laboratorial e, também, investigar a etiologia da mesma e os fatores associados. Os participantes faziam parte de uma coorte acompanhada desde o nascimento e foram incluídos neste estudo por apresentar, em acompanhamentos anteriores, suspeita de atraso no desenvolvimento segundo o Teste de Rastreamento de Battelle, QI abaixo de 70 segundo a escala WPPSI e/ou problemas no comportamento observados durante entrevista. Das 4231 crianças da Coorte de 2004 de Pelotas, 214 foram selecionadas para a avaliação genética que constou de: anamnese, exame físico e dismorfológico e coleta de sangue e urina quando indicado. Criou-se um banco de dados incluindo variáves desta avaliação e dos acompanhamentos anteriores da Coorte, tais como: variáveis da gestação e do nascimento, sociodemográficas e relativas à saúde e estimulação da criança. Os dados foram processados no pacote estatístico Stata 13.0 e foi utilizada análise de variância (ANOVA). Foi considerada como tendo deficiência intelectual a criança que, além de apresentar um QI abaixo de 70, apresentava também problemas no comportamento adaptativo. Cento e setenta crianças das duzentas e quatorze selecionadas no início do estudo foram diagnosticadas com deficiência intelectual e classificadas em cinco grupos etiológicos. A maior parte das crianças (44,4%) foi classificada como tendo deficiência intelectual devida a causas não-biológicas, ou seja, ligada a fatores ambientais. O segundo maior grupo (16,6%) foi o grupo de crianças com deficiência intelectual genética que incluiu crianças com síndrome de Down, microdeleções e patologias autossômicas dominantes e patologias multifatoriais. A seguir, crianças com sequelas neonatais (13,3%) e deficiência intelectual associada a outras doenças (13,3%), como epilepsia e TDAH. O menor grupo foi o idiopático, constituído por crianças que, mesmo após investigação clínica e laboratorial, permaneceram sem diagnóstico definido. A prevalência de deficiência intelectual foi de 4,5% e a prevalência de deficiência intelectual genética de 0,66%. Apesar de algumas limitações como a identificação e seleção dos casos aos 4 anos para uma avaliação aos 7-8 anos, é importante considerar que, por ser um estudo de base populacional, com alta taxa de acompanhamento (92,0%), isto minimiza o viés de seleção. O fato dos dados serem colhidos no momento ou em um curto intervalo de tempo, considerando os diversos acompanhamentos, minimiza o viés de memória. Fora do mundo desenvolvido, são raros os estudos de coorte que avaliaram deficiência intelectual, seus fatores de risco e sua etiologia. Grande parte destes estudos, mesmo os conduzidos em países de renda alta, avaliaram a prevalência, mas não a etiologia. Os dados sugerem que boa parte destes casos poderia ser prevenida, principalmente considerando uma etiologia não-biológica, caso existissem, além do rastreamento de problemas no desenvolvimento, estratégias de intervenção educacional e de saúde. / The aims of this study were to estimate the prevalence and etiology of intellectual disability at 7-8 years of age in a birth cohort through clinical and laboratory investigation and associated factors. Participants were part of a cohort followed from birth and were included in this study due to suspected developmental delay according to the Battelle Screening Test, IQ below 70 according to WPPSI scale and / or behavior problems observed during the interview in previous follow-ups. Of the 4231 children in the 2004 Pelotas birth cohort, 214 were selected for genetic evaluation which included anamnesis, physical and dysmorphological examination and collection of blood and urine when indicated. A dataset including variables from this evaluation and the previous cohort of follow-ups such as variables of pregnancy and birth, social demographic and health-related and stimulation of the child. Data were analyzed using Stata version 13.0. Analysis of variance (ANOVA) was performed. To be considered as having intellectual disability the child that presenting an IQ below 70 and problems in adaptive behavior. One hundred and seventy children from two hundred fourteen selected at baseline were diagnosed with intellectual disability and they were classified into five etiologic groups. Most children (44.4 %) were classified as having intellectual disability due to no biological causes, i.e., linked to environmental factors. The second largest group (16.6%) was the group of children with genetic intellectual disability which included children with Down syndrome, microdeletions and autosomal dominant and multifactorial diseases. Children with neonatal sequelae accounted for 13.3% and intellectual disability associated with other diseases such as epilepsy and ADHD also accounted for 13.3%. The smallest group was idiopathic composed of children who even after clinical and laboratory investigation remained without a definite diagnosis. The prevalence of intellectual disability was 4.5 % and the prevalence of genetic intellectual disability 0.66 %. Despite some limitations such as the identification and selection of cases to four years for an assessment at 7-8 years it is important to consider that it is a population-based study with high follow-up rate (92.0 %) which minimizes selection and information bias. As data were collected in time or in a short period of time considering the several follow-ups minimize recall bias. Outside the developed world few cohort studies assessed intellectual disabilities, their risk factors and etiology. Most of these studies even those conducted in high-income countries assessed the prevalence but not the etiology. The data suggest that part of these cases could be prevented specially considering the non-biological etiology if there were screening of developmental delay and intervention strategies on health and educational bases.

Estudamos uma família com cinco homens (dois falecidos) afetados por deficiência mental (DM) não-sindrômica em duas gerações, num padrão de herança ligada ao cromossomo X. A análise do padrão de inativação do cromossomo X, com base na metilação do gene AR, evidenciou que a mulher portadora obrigatória tinha desvio completo de inativação nos leucócitos, uma característica freqüente em portadoras de mutações do cromossomo X relacionadas com DM. Para o mapeamento da DM, genotipamos 28 locos de microssatélites ao longo do cromossomo X e delimitamos um segmento de cerca de 32 Mb, entre os marcadores DXS986 e DXS8067, compartilhado pelos afetados e pela portadora obrigatória, mas não pelo homem normal ou pelas possíveis portadoras que não tinham desvio do padrão de inativação do cromossomo X. Na busca do gene mutado, analisamos, por seqüenciamento direto, genes mapeados no intervalo compartilhado e já relacionados a DM ou que tivessem expressão em cérebro e leucócitos. Nos afetados e na portadora obrigatória, encontramos a mutação c.845C→T no gene ACSL4, que resulta na substituição do aminoácido histidina, conservado na família de sintetases de acil-CoA humanas e em diversos outros organismos, por tirosina (p.H323Y da isoforma cérebro-específica). Tratando-se de mutação que altera um aminoácido evolutivamente conservado em gene já relacionado com DM, que segregava com a DM na família, não tendo sido encontrada em amostra controle de 160 indivíduos do sexo masculino, concluímos que era a causa da DM na família. Mutações de ponto no gene ACSL4 foram relacionadas com a DM não sindrômica em três famílias descritas na literatura. O gene ACSL4 codifica a acil-coA sintetase 4 da família das sintetases de cadeia longa, que catalisa a formação de ésteres acil-coA a partir de ácidos graxos de cadeia longa. Sua expressão já foi documentada em vários tecidos, incluindo o cérebro e dados recentes mostraram que a proteína é essencial para a formação normal de espinhos dendríticos. A nova mutação do gene ACSL4 que descrevemos como causa de DM vem reforçar a relação alterações desse gene e a DM de herança ligada ao X. O padrão de inativação do X totalmente desviado foi mais uma vez observado em mulher portadora da mutação, indicando a importância da expressão desse gene em leucócitos. A presença de dificuldades de aprendizado na portadora da mutação concorda com o observado nas três famílias da literatura em que o estudo das portadoras foi relatado, indicando o efeito de mutações do gene ACSL4 sobre a função intelectual mesmo em heterozigose. A ausência de correlação entre o padrão de inativação do cromossomo X em células do sangue periférico e o comprometimento intelectual foi confirmada. Na família estudada, a identificação da mutação permitiu o aconselhamento genético. / We studied a family with five men (two of them deceased) affected by nonsyndromic mental retardation in two generations, in a pattern of X-linked inheritance (MRX). The study aimed at identifying the causative mutation. The obligate female carrier showed completely skewed inactivation of the X chromosome, based on the methylation status of the AR gene in peripheral blood in leukocytes, a common feature in carriers of X-linked mutations that cause mental retardation. We genotyped 28 microsatellite loci mapped throughout the X chromosome and delimited a 32 Mb segment, between markers DXS986 and DXS8067, that was shared by the affected males and obligate carrier, but was not present in a normal man or in two women who did not show skewed X-inactivation. We searched for the causative mutation by sequencing genes mapped to this candidate interval that had been associated with MR and/or were expressed in brain and leukocytes. In the affected men and obligate carrier, we found a c.845C→T mutation in the ACSL4 gene, resulting in the amino acid tyrosine substituting for a histidine (p.H323Y in brain isoform), which is conserved in the acyl-CoA synthetase family in humans and others organisms. This mutation was not found in a control sample of 160 men. Previously, point mutations in the ACSL4 gene had been identified as the cause of MRX in three families. ACSL4 encodes the acyl-CoA synthetase long-chain family member 4, which catalyzes the formation of acyl-CoA esters from long-chain fatty acids. It is expressed in several tissues, and in brain it is essential for the normal formation of dendritic spines. The novel mutation here described confirmed the causal association of ACSL4 mutations with non-syndromic mental retardation. The completely skewed Xinactivation, also observed in the previously described carriers, supported a functional role for this gene in peripheral blood leukocytes. The intellectual impairment present in the carrier in the family here reported is in accordance with previous findings pointing to the effect on intellectual abilities of ACSL4 mutations in heterozygosis. The absence of correlation between the pattern of X-inactivation in leukocytes and mental status was confirmed.

No description available.

The purpose of this study was to investigate the extent to which a non-verbal test of intelligence, the Test of Non-Verbal Intelligence (TONI), may be used for assessing intellectual abilities of children in India. This investigation is considered important since current instruments used in India were developed several years ago and do not adequately reflect present standards of performance. Further, current instruments do not demonstrate adequate validity, as procedures for development and cultural transport were frequently not in adherence to recommended guidelines for such practice. Data were collected from 91 normally achieving and 18 mentally retarded Indian children, currently enrolled in elementary schools. Data from an American comparison group were procured from the authors of the TONI. Subjects were matched on age, grade, and area of residence. Subjects were also from comparative socioeconomic backgrounds. Literature review of the theoretical framework supporting cross-cultural measurement of intellectual ability, a summary of major instruments developed for cross-cultural use, non-verbal measures of intellectual ability in India, and issues in cross-cultural research are discussed, with recommended methodology for test transport. Major findings are: (a) the factor scales derived from the Indian and American normally achieving groups indicate significant differences; (b) items 1, 3, 5, 8, 10, and 22 are biased against the Indian group, though overall item characteristic curves are not significantly different; (c) mean raw scores on the TONI are significantly different between second and third grade Indian subjects; and (d) mean TONI Quotients are significantly different between normally achieving and mentally retarded Indian subjects. It is evident that deletion of biased items and rescaling would be necessary for the TONI to be valid in the Indian context. However, because it does discriminate between subjects at different levels of ability, adaptation for use in India is justified. It may prove to be a more current and parsimonious method of assessing intellectual abilities in Indian children than instruments presently in use.