Supportive evidence for the DYX3 dyslexia susceptibility gene in Canadian families.
Explore the source record for details and available documents.
Canada↗
Biomedical subjects
B J Kaplan
Publications and source records attributed to B J Kaplan.
Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia.
A linkage study of 96 dyslexia families containing at least two affected siblings (totaling 877 individuals) has found evidence for a dyslexia susceptibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qualitative phonological coding dyslexia (PCD) phenotype (affected, unaffected, or uncertain diagnoses), two-point parametric analyses found highly suggestive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LOD(max) scores = 2.4 to 2.8) across an 11 cM region. Multipoint parametric analysis supported linkage of PCD to this region (peak HLOD = 1.6), as did multipoint nonparametric linkage analysis (P = 0.012). Quantitative trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also provided evidence for a dyslexia susceptibility locus on chromosome 6q. Using a variance-component approach, analysis of phonological coding and spelling measures resulted in peak LOD scores at D6S965 of 2.1 and 3.3, respectively, under 2 degrees of freedom. Furthermore, multipoint nonparametric quantitative trait sibpair analyses suggested linkage between the 6q region and phonological awareness, phonological coding, and spelling (P = 0.018, 0.017, 0.0005, respectively, for unweighted sibpairs < 18 years of age). Although conventional significance thresholds were not reached in the linkage analyses, the chromosome 6q11.2-q12 region clearly warrants investigation in other dyslexia family samples to attempt replication and confirmation of a dyslexia susceptibility gene in this region.
Adolescent↗
Predictive accuracy of the wide range assessment of memory and learning in children with attention deficit hyperactivity disorder and reading difficulties.
The predictive accuracy of the Wide Range Assessment of Memory and Learning (WRAML; Sheslow & Adams, 1990) over and above more standardized diagnostic tools in children with attention deficit hyperactivity disorder (ADHD) and reading disabilities (RD) was examined. Fifty-three children with ADHD, 63 with RD, 63 with ADHD-RD, and 112 normal comparison children were administered the WRAML, the Wechsler Intelligence Scale for Children-Third Edition (WISC-III; Wechsler, 1991), the Achenbach (1991) Child Behavior Checklist (CBCL), and the Woodcock-Johnson Psycho-Educational Battery-Revised (WJ-R; Woodcock & Johnson, 1989). Results of a series of discriminant function analyses revealed that the academic, intellectual, and behavioral measures could correctly classify 73.1% of children, but the WRAML subtests alone were able to correctly classify only 58.5% of participants. Combining all of the memory, academic, intellectual, and behavioral measures resulted in 77.5% of cases being correctly classified. These results suggest that the use of a measure of memory functioning such as the WRAML did not significantly improve the predictive accuracy of a diagnosis of ADHD, RD, or both over and above more standard diagnostic academic, intellectual, and behavioral measures.
Attention Deficit Disorder with Hyperactivity↗
Atypical brain development: a conceptual framework for understanding developmental learning disabilities.
This article presents ideas that are, in part, a response to the ambiguity in the neurological research on learning disorders, the growing awareness that developmental disabilities are typically nonspecific and heterogeneous, and the growing scientific literature showing that comorbidity of symptoms and syndromes is the rule rather than the exception. This article proposes the term atypical brain development (ABD) as a unifying concept to assist researchers and educators trying to come to terms with these dilemmas. ABD is meant to serve as an integrative concept of etiology, the expression of which is variable within and across individuals. ABD does not itself represent a specific disorder or disease. It is a term that can be used to address the full range of developmental disorders that are found to be overlapping much of the time in any sample of children. Although similar in spirit to the older term of minimal brain dysfunction (MBD), in that it closely links neurology with behavioral difficulties, ABD as proposed here differs in several ways. In support of the ABD conceptual framework, first, we consider the ABD concept in terms of its superiority to the older notion of MBD. Second, we provide a brief review of the burgeoning literature on the overlap of the various developmental disabilities. Third, we review some of the scientific literature that supports the ABD concept. Our sole purpose in proposing this concept is to initiate dialogue and debate on several critical issues across a wide variety disciplines. Hence, this article is not intended to be a definitive statement of a rigid perspective. It reflects neither a nonmalleable philosophical position, nor any type of condemnation of other perspectives. It does, however, reflect a data-based and philosophical trend visible in the field of learning disabilities, as well as the broader area of childhood developmental disorders.
Attention Deficit Disorder with Hyperactivity↗
Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder.
BACKGROUND: To determine in open trials the therapeutic benefit of a nutritional supplement for bipolar disorder. METHOD: The sample consisted of 11 patients with DSM-IV-diagnosed bipolar disorder aged 19 to 46 years, who were taking a mean of 2.7 psychotropic medications each at study entry. Three additional patients dropped out prematurely. The intervention is a broad-based nutritional supplement of dietary nutrients, primarily chelated trace minerals and vitamins, administered in high doses. At study entry and periodically thereafter, patients were assessed with the Hamilton Rating Scale for Depression (HAM-D), the Brief Psychiatric Rating Scale (BPRS), and the Young Mania Rating Scale (YMRS). RESULTS: For those who completed the minimum 6-month open trial, symptom reduction ranged from 55% to 66% on the outcome measures; need for psychotropic medications decreased by more than 50%. Paired t tests revealed treatment benefit on all measures for patients completing the trial: HAM-D mean score at entry = 19.0, mean score at last visit = 5.4, t = 5.59, df = 9, p < 01; BPRS mean score at entry = 35.3, mean score at last visit = 7.4, t = 2.57, df = 9, p <.05; YMRS mean score at entry = 15.1, mean score at last visit = 6.0, t = 4.11, df = 9, p < .01. The effect size for the intervention was large (> .80) for each measure. The number of psychotropic medications decreased significantly to a mean +/- SD of 1.0+/-1.1 (t = 3.54, df = 10, p < .01). In some cases, the supplement replaced psychotropic medications and the patients remained well. The only reported side effect (i.e., nausea) was infrequent, minor, and transitory. CONCLUSION: Some cases of bipolar illness may be ameliorated by nutritional supplementation. A randomized, placebo-controlled trial in adults with bipolar I disorder is currently underway, as well as open trials in children.
Adult↗
Attributions and perceptions of childhood in women with ADHD symptomatology. Attention-Deficit/Hyperactivity Disorder.
Now that it is recognized that Attention-Deficit/Hyperactivity Disorder (ADHD) often persists into adulthood, there are many adults being identified with ADHD who were not diagnosed as children. Individuals identified with ADHD during adulthood may be at risk for maladaptive attributional styles based on the notion that they were exposed to more negative feedback during childhood than adults without identified ADHD. This study examined current attributions and perceptions of childhood of 51 women identified in adulthood with ADHD symptomatology and 51 nonADHD women. Women with ADHD symptomatology had more uncontrollable, stable, and global attributions, reported more dissatisfaction in their childhood parent, peer, and teacher relationships, and felt less in control of negative childhood events as compared with the nonADHD women. Both depression and ADHD contributed significantly to these group differences, suggesting that negative perceptions and attributions are more than reflections of current thinking and mood. ADHD symptomatology also may be an important risk factor for maladaptive attributions.
Adult↗
Absence of significant linkage between phonological coding dyslexia and chromosome 6p23-21.3, as determined by use of quantitative-trait methods: confirmation of qualitative analyses.
We recently reported the absence of significant linkage of phonological coding dyslexia (PCD) to chromosome 6p23-p21.3 in 79 families with at least two affected siblings, even though linkage of dyslexia to this region has been found in four other independent studies. Whereas, in our previous analyses, we used a qualitative (affected, unaffected, or uncertain) PCD phenotype, here we report a reanalysis of linkage to the chromosome 6p region, by use of four quantitative measures of reading disability: phonological awareness, phonological coding, spelling, and rapid-automatized-naming (RAN) speed. The phonological-coding and spelling measures were highly correlated with each other and with the qualitative PCD phenotype, whereas the phonological-awareness and RAN-speed measures were only moderately correlated with the other measures. Using two-point and multipoint quantitative-trait sib-pair linkage analyses and variance-components analyses, we were unable to detect significant evidence for a locus in the 6p23-p21.3 region influencing any of the quantitative reading measures, supporting our previous qualitative linkage results. The most likely explanation for our inability to detect linkage between dyslexia and this region is that families with subtypes of dyslexia linked to this region are underrepresented in our sample, because of either chance or varying ascertainment criteria.
Adolescent↗
Deficits in long-term memory are not characteristic of ADHD. Attention Deficit Hyperactivity Disorder.
To separate the influence of inattentiveness from memory, we examined savings scores on material previously learned in 53 children with Attention Deficit Hyperactivity Disorder (ADHD), 63 with a reading disability (RD), 63 with both ADHD and RD combined, and 112 controls. Children with reading disabilities were impaired in their ability to remember previously-learned material unless it was repeated over four trials, whereas children with only ADHD performed as well as the controls for material presented only once. Children with ADHD did perform poorly on three subtests that are sensitive to attention/ concentration. We conclude that ADHD is associated with impaired initial learning due to attention deficits, but that long-term retention of learned material is normal.
Attention Deficit Disorder with Hyperactivity↗
Absence of linkage of phonological coding dyslexia to chromosome 6p23-p21.3 in a large family data set.
Previous studies have suggested that a locus predisposing to specific reading disability (dyslexia) resides on chromosome 6p23-p21.3. We investigated 79 families having at least two siblings affected with phonological coding dyslexia, the most common form of reading disability (617 people genotyped, 294 affected), and we tested for linkage with the genetic markers reported to be linked to dyslexia in those studies. No evidence for linkage was found by LOD score analysis or affected-sib-pair methods. However, using the affected-pedigree-member (APM) method, we detected significant evidence for linkage and/or association with some markers when we used published allele frequencies with weighting of rarer alleles. APM results were not significant when we used marker allele frequencies estimated from parents. Furthermore, results were not significant with the more robust SIMIBD method using either published or parental marker frequencies. Finally, family-based association analysis using the AFBAC program showed no evidence for association with any marker. We conclude that the APM method should be used only with extreme caution, because it appears to have generated false-positive results. In summary, using a large data set with high power to detect linkage, we were unable to find evidence for linkage or association between phonological coding dyslexia and chromosome 6p markers.
Alberta↗
Absence of an association between IgE-mediated atopic responsiveness and ADHD symptomatology.
There are mixed research results in the literature regarding a possible association between Attention Deficit Hyperactivity Disorder (ADHD) and atopic disorders. If such an association were supported, the implications for underlying pathophysiology would be significant. We evaluated level of atopic responsiveness (based on IgE-mediated response to skin prick tests) in 312 referrals to a pediatric allergist. Based on the atopy code, children were categorized as non-atopic, or moderately or severely atopic. Parents completed the Child Behavior Checklist (CBCL). Univariate analyses on the eight CBCL subscales revealed no differences between the atopic groups. Our results do not support an association between IgE-Mediated atopic responsiveness and ADHD, but they do not rule out an association between allergic symptoms and ADHD based on some other mechanism.
Adolescent↗
The influence of systemic lupus erythematosus on fetal development: cognitive, behavioral, and health trends.
In 1985, Gualtieri and Hicks proposed the immunoreactive theory to explain the higher prevalence of childhood neurodevelopmental disorders in males. The theory claimed that male fetuses are more antigenic to mothers, resulting in increased immunologic attack on the developing central nervous system, and increased probability of atypical brain development. Individuals with systemic lupus erythematosus (SLE) provide a unique situation in which to investigate this theory. We evaluated the parent-reported prevalence of five developmental problems (stuttering, other speech problems, hyperactivity, attention deficit, and reading problems) in two groups: 154 individuals ages 8-20 years born to women with SLE, drawn from six cities, and 154 controls of comparable age and sex whose mothers did not have SLE. Controls were drawn from a comparison group ascertained from randomly selected schools in one of the cities. Questions about handedness, immune disorders, and pregnancy and birth complications were also evaluated. Children of SLE mothers were shown to have more evidence of developmental difficulties, immune related disorders, and nonrighthandedness. For developmental problems, these findings were most marked in male children of SLE mothers. These results suggest that maternal immunoreactivity, as represented by women with SLE, may present a special risk factor for subsequent learning difficulties in their children, particularly males.
Adolescent↗
Somatosensory evoked potential monitoring during carotid surgery.
Controversy exists over the value of intraoperative monitoring and shunting in patients undergoing carotid endarterectomy. Although it is widely believed that contralateral carotid occlusion and previous stroke mandate intraoperative shunting, the susceptibility of these two groups of patients to cerebral ischemia during carotid artery endarterectomy is not well defined. Somatosensory evoked potentials (SSEPs) were monitored in 113 carotid artery endarterectomy patients. Of these, 32 (28.3%) had a previous stroke, 24 (21.2%) had a contralateral carotid occlusion and 33 (29.2%) were diabetic. There were no deaths and only one perioperative stroke (0.9%). Cerebral ischemia occurred in 14 patients (12.4%). Six of these patients had a contralateral carotid occlusion. Some 29 patients (25.7%) were shunted, including 10 with contralateral carotid occlusions that did not have major SSEP changes. In the latter half of the study, 14 patients with contralateral carotid occlusions were selectively shunted (six shunted, eight not shunted) with no neurological complications. Thirty-two patients with prior strokes were selectively shunted (nine shunted, 23 not shunted); of these, one shunted patient undergoing combined carotid artery endarterectomy and coronary artery bypass grafting had a perioperative stroke. Intraoperative monitoring with SSEPs accurately identifies cerebral ischemia secondary to carotid clamping as well as patients requiring shunts. With use of intraoperative SSEP monitoring, selective shunting may be safely performed in patients with a contralateral carotid occlusion or a previous stroke.
Adult↗
Possessed by the devil? A very public dispute in Utrecht.
Explore the source record for details and available documents.
History, 17th Century↗
Polyps and polypoid lesions of the jejunum and ileum. Clinical aspects.
Polyps and polypoid lesion of the small intestine present a major challenge to the surgeon. In contrast to similar lesions in the large intestine, small bowel polyps present late in their course and are difficult to diagnose. Small bowel tumors produce vague symptoms and screening tests are poor. Most of these polyps are found at autopsy or during exploration for another cause. In this article, the authors outline the problem as well as discuss the diagnosis and treatment options.
Adenomatous Polyposis Coli↗
Absence of an association between insulin-dependent diabetes mellitus and developmental learning difficulties.
For several years, investigators have been examining the relationship between learning difficulties and a variety of immunological disorders. Two recent studies by Hansen and colleagues reported a negative association between Type 1 diabetes and reading disabilities (dyslexia): subjects with Type 1 diabetes had a lower prevalence of dyslexia than their nondiabetic relatives. In order to control for the impact of environmental variables on learning, we investigated the relationship between Type 1 diabetes and learning problems in 27 sibling pairs, ranging in age from 6 to 20 years. One child in each pair had Type 1 diabetes, and the other child was the unaffected sibling closest in age. Children were assessed for cognitive skills, academic achievement in reading, mathematics, and written language, as well as for speech articulation and motor coordination. Other variables that were examined included handedness, behavioural variables, medical history, and pregnancy and birth complications. We found no significant differences between the 27 children with Type 1 diabetes and their unaffected siblings on any of the cognitive, academic achievement, or speech articulation measures. There were also no significant differences on handedness, behavioural variables, or health history.
Child↗
Use of the Bruininks-Oseretsky test of motor proficiency in occupational therapy.
OBJECTIVE: In addition to the need for good measurement tools in occupational therapy, there is a need for the tools to be used knowledgeably. The purpose of this article is to investigate the usefulness of the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) for both descriptive (diagnostic) and evaluative (change over time) purposes. METHOD: The typical profile of subtest scores for children with mild motor problems revealed that certain subtests of the BOTMP may be better indicators of motor problems for these children than others. An analysis also was performed to compare the use of raw (point) scores with standard (age-adjusted) scores in evaluating change. RESULTS: Four subtests that provide a greater degree of discrimination between children with and without motor problems were identified. Raw (points) scores were found to provide a more valid measure of change over time than standard (age-related) scores. CONCLUSION: We recommend that, for clinical use, the BOTMP subtest standard scores be used for diagnostic purposes and that the raw scores be used for evaluative purposes.
Analysis of Variance↗
The GBG model: is there more to consider than handedness?
It is peculiar that Bryden and his colleagues admit to the inadequacy of handedness as an index for cerebral anomalous dominance and then attack a model of anomalous dominance using primarily handedness data. In reality, the GBG model (which was intended to be "a hypothesis and program for research," to quote the exact titles of the 1985 articles) is not nearly as narrow as Bryden's worldview. We present here the rest of the literature on the link between immune disorders and language disorders which Bryden et al. neglected and argue that the data are sufficient to have warranted a +2 in their evaluation. The strength of this link is worthy of further investigation, even though the hormonal mechanism proposed in the GBG model may be erroneous.
Animals↗
Are families of children with reading difficulties at risk for immune disorders and nonrighthandedness?
This study used questionnaire data to examine immune disorders and nonrighthandedness in the families of children enrolled in a learning disabilities school and children attending regular classrooms in public schools. Groups were organized according to their performance on a standardized test of reading comprehension to avoid overlap. In total, 468 questionnaires were returned, from which we were able to derive a final sample of carefully matched subjects: 55 subjects undergoing remediation for reading problems and 55 age- and sex-matched control subjects. The results indicated that children with reading problems and their families more frequently suffered from some immune and autoimmune disorders, particularly those involving the gastrointestinal tract and the thyroid gland. In addition, symptoms of attention deficit hyperactivity disorder were associated with Crohn's disease and migraine headache in the families. There was no evidence of an elevated prevalence of nonrighthandedness in the children with reading problems and their families.
Adolescent↗