Genotype-phenotype correlations in RHOBTB2-associated neurodevelopmental disorders

PurposeMissense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability.MethodsBy international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro.ResultsIn accordance with previous observations, de novo heterozygous missense variants in the BTB domain region led to a severe developmental and epileptic encephalopathy in 16 individuals. Now, we also identified de novo missense variants in the GTPase domain in 6 individuals with apparently more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences. Furthermore, we observed biallelic splice-site and truncating variants in 9 families with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well.ConclusionBy identifying genotype-phenotype correlations regarding location and consequences of de novo missense variants in RHOBTB2 and by identifying biallelic truncating variants, we further delineate and expand the molecular and clinical spectrum of RHOBTB2-related phenotypes, including both autosomal dominant and recessive neurodevelopmental disorders.     

Somatic symptoms,pain, catastrophizing and the association with disability among children with heritable connective tissue disorders

The aim of the present study was to investigate the nature and prevalence of nonspecific somatic symptoms, pain and catastrophizing in children with Heritable Connective Tissue Disorders (HCTD), and to determine their association with disability. This observational, multicenter study included 127 children, aged 4–18 years, with Marfan syndrome (MFS) (59%), Loeys-Dietz syndrome (LDS) (8%), Ehlers-Danlos syndromes (EDS) (12%) and hypermobile Ehlers-Danlos syndrome (hEDS) (23%). The assessments included the Children's Somatization Inventory or parent proxy (CSI, PCSI), pain visual-analogue scale (VAS), SUPERKIDZ body diagram, Pain Catastrophizing Scale Child or parent proxy (PCS-C, PCS-P) and Childhood Health Assessment Questionnaire (CHAQ-30). Data from children aged ≥8 years were compared to normative data. In children ≥ 8 years (n = 90), pain was present in 59%, with a median of 4 (IQR = 3–9) pain areas. Compared to normative data, the HCTD group reported significantly higher on the CSI (p ≤ 0.001, d = 0.85), VAS pain intensity (p ≤ 0.001, d = 1.22) and CHAQ-30 (p ≤ 0.001, d = 1.16) and lower on the PCS-C (p = 0.017, d = −0.82) and PCS-P (p ≤ 0.001, d = −0.49). The intensity of nonspecific somatic symptoms and pain explained 45% of the variance in disability (r² = 0.45 F(2,48) = 19.70, p ≤ 0.001). In children ≤ 7 years (n = 37), pain was present in 35% with a median of 5(IQR = 1–13) pain areas. The mean(SD) VAS scores for pain intensity was 1.5(2.9). Functional disability was moderately correlated to the number of pain areas (r = 0.56, p ≤ 0.001), intensity of nonspecific somatic symptoms (r = 0.63, p ≤ 0.001) and pain (r = 0.83, p ≤ 0.001). In conclusion, this study supports the need for comprehensive assessment of nonspecific somatic symptoms, pain, and disability in children with HCTD to allow tailored treatment.     

Etiology of individual differences in reading performance: A test of sex limitation

To test the hypothesis that the etiology of individual differences in reading performance differs in males and females, reading performance data from twin pairs tested in the Colorado Learning Disabilities Research Center were fitted to structural equation models of sex limitation. The sample included 513 pairs of twins in which at least one member of each pair has a positive school history of reading problems [228 monozygotic (MZ), 176 same-sex dizygotic (DZ), and 109 opposite-sex DZ pairs] and 302 matched control pairs [148 MZ, 98 same-sex DZ, and 56 opposite-sex DZ pairs]. Estimates of the genetic correlation between performance in males and females were obtained by analysis of data from both same-sex and opposite-sex twin pairs (Neale and Cardon, 1992). The full model fit the data well ²=17,74, df=16,p=0.340), and the resulting genetic parameter estimates were highly similar in males and females in both the proband and the control samples. The correlations between genetic influences in males and females do not differ among groups (change in ²=0.95, df=1,p0.25), and the resulting pooled estimate is about .5. Thus, results of this analysis suggest that the etiology of individual differences in reading performance may differ to some extent in males and females.     

Social construction of Anangu disability

ABSTRACT: The usual and common-sense definition of disability is based on a medical model that sees disability as a limitation or lack of competence on the part of the individual. This definition fails to acknowledge that in some cultures disability as a concept does not exist. This paper, based on research undertaken in 1994/1995, examines how the social construction of disability among the A n angu of the cross border region of Western Australia, South Australia and the Northern Territory, takes into consideration the important factors of history, culture and language. The theoretical underpinning of the research was symbolic interactionism, which led to collaborative ethnography becoming the methodology employed to collect and analyse the data. The findings of the research indicate that the social construction of disability among the A n angu occurs in three historical phases: the impairment, oppression and empowerment phases. The paper's purpose is to offer service providers to Aboriginal people with disabilities, information that will help them understand some of the attitudes, customs, mores and beliefs of their clientele.     

Disability-Job Fit Stereotypes and the Evaluation of Persons with Disabilities at Work

The present paper describes a laboratory experiment in which raters evaluated the videotaped performance of ratees who did or did not have a disability. This disability was stereotypically either a poor fit with the job in question or not. The results indicated that actual appraisals were not influenced by stereotypes about fit or by disabilities, but that expectations concerning future performance and a number of other decisions and recommendations were influenced by this perceived fit. These results suggest that people do hold clear stereotypes about what types of disabilities lead to poor performance on a given job, and that these stereotypes are relied upon for certain personnel decisions, even in light of performance evidence that suggests that these stereotypes are invalid. Employees' disabilities may not influence supervisors' evaluations of their past performance when supervisors have clear objective performance information available. However, bias still exists in expectations for future performance and training recommendations. This bias can have severe long-term consequences on one's career within an organization. The scenario is worse when one's disability is stereotypically believed to be unsuitable to the job in question.     

Differential parental communication with adolescents who are disabled and their healthy siblings

Purpose: To examine the levels of parental communication and differential conversational styles with adolescents who are disabled and their healthy siblings, to better understand why the adolescent who is disabled has a higher risk of psychosocial problems during the transition into adulthood.

Methods: Families who had a disabled adolescent and at least one other adolescent who was not disabled were videorecorded during dinner at home. Twenty adolescents (12 girls and 8 boys) and their families participated. Analyses were conducted on the 392 interactions.

Results: Not only did the healthy adolescents participate in family interactions at higher frequencies than the adolescents who were disabled F(1, 383) = 14.00, p < .001, but the interactions were also more meaningful with healthy adolescents, F(2, 383) = 5.25, p < .01. Furthermore, healthy siblings had significantly greater conversational control than did their siblings with disabilities, χ² [1] = 14.36, p < .001. Parents responded more negatively when adolescents who were disabled initiated a topic in comparison with their response to the healthy siblings, F(2, 69) = 5.44, p < .01. Finally, adolescents with disabilities were ignored more often than their healthy siblings, z = −3.75, p < .001, and they did not monopolize the conversation as often as did their healthy siblings, z = −3.91, p < .001.

Conclusion: These results suggest that adolescents who are disabled may be at a disadvantage when engaged in family interactions in contrast with their healthy siblings.     

Sexual Knowledge,Experience and Feelings Among People with Disability

The current study was designed to evaluate the sexual knowledge, experience, feelings and needs of people with intellectual disability or physical disability, and compare them to people from the general population. Sixty people with mild intellectual disability (28 males, 32 females, mean age=27.62 years), 60 people with physical disability (33 males, 27 females, mean age=28.65 years) and 100 people from the general population (40 males, 60 females, mean age=30.10 years) participated in the study. Each respondent completed the Sexual Knowledge, Experience and Needs Scale (SexKen). This scale assesses levels of knowledge, experience, feelings and needs in 12 different areas of sexuality. The results demonstrated that people with intellectual disability experienced lower levels of sexual knowledge and experience, more negative attitudes to sex and stronger sexual needs than people with physical disability, in all areas of sexuality. People with physical disability demonstrated these same trends when they were compared to people from the general population. An interpretation of these results as they relate to the sexuality of people with intellectual or physical disability is provided.     

More than just a health issue: a review of current issues in the care of enterally-fed children living in the community

There are increasing numbers of children with a disability living in the community who require enteral tube feeds to optimize their nutritional status. Whilst there appears to be evidence of health gains, for some children there may also be serious and unintended social deprivations resulting from the need to be tube fed. This paper reviews the literature on support for children who are tube fed and makes a case for more coordinated and effective support services for families who are tube feeding a child at home. It is argued that national guidance should be developed which clarifies the position of all non-parent carers and staff who are willing to administer enteral tube feeds. Such guidance should also ensure that enterally-fed children have the same rights to educational and social services as other children and that families are given the opportunity to make informed decisions about the implications of enteral feeding prior to it being established.