The inequity of education, health and care plan provision for children and young people with intellectual and developmental disabilities.

BACKGROUND: Children and young people (CYP) with intellectual and developmental disabilities (IDDs) have significant additional educational needs compared with the general population. In England, the government has established a system of education, health and care plans (EHCPs) to support children with special educational needs and disabilities, but disparities exist between the degree of need and the availability of support. We conducted a prospective UK national cohort study (IMAGINE) of children with rare pathogenic genomic variants, all of which are associated with IDD, to investigate associated neuropsychiatric risk. Subsequently, we obtained information from the UK's National Pupil Database on their educational progress through the state school system. We aimed to identify whether they had received EHCP provision and whether that support was associated with their family's socioeconomic status, region of domicile, ethnicity, sex, primary special educational needs (SEN) type, academic performance and mental health well-being. METHODS: We recruited 2738 CYP from England into the IMAGINE study between 2014 and 2019. The educational histories of the participants (6-28 years old, mean ± standard deviation = 14 ± 4 years, 56% male) were obtained from the Department for Education's National Pupil Database in 2021. Educational data included attainment scores from the Early Year Foundation Stage (<5 years) to key stage 4 (15-16 years). Each family was assigned an index of multiple deprivation (IMD) score based on their home address postcode. Parents or carers rated their child's emotional and behavioural adjustment on the Strengths and Difficulties Questionnaire (SDQ). The association between receiving an EHCP and the child's IMD score, eligibility for free school meals, English region of domicile, ethnicity, sex, primary SEN type, academic attainment and SDQ score was investigated. RESULTS: In this cohort, 78% of participants had received an EHCP. CYP living in the most deprived IMD deciles were substantially less likely to receive EHCP support than those in the least deprived decile, irrespective of their degree of intellectual developmental disability, academic performance or associated mental health problems. There were no sex differences. Children of Asian heritage were more likely to have been granted an EHCP than White children from equivalent IMD deciles. There were striking regional disparities. Participants living in London were significantly more likely to have been awarded an EHCP than participants living anywhere else in England, regardless of their IMD decile; those in the least deprived decile had almost 100% EHCP provision. CONCLUSIONS: This study found evidence for nationwide regional inconsistencies in the awarding of EHCP to CYP with significant intellectual impairments of known genetic aetiology. Disparities in funds available to education authorities could be a contributory factor. EHCP support was potentially influenced by how strongly a parent advocates for their child.

Social communication deficits in disruptive primary-school children.

BACKGROUND: Parent and teacher data, from questionnaire surveys, suggest that school-identified disruptive children often have pragmatic language deficits of an autistic type. AIMS: This replication study aimed to confirm earlier findings, using individual clinical assessment to investigate traits of autism-spectrum disorder in disruptive children. METHOD: Persistently disruptive children (n = 26) and a comparison group (n = 22) were recruited from primary schools in a deprived inner-city area. Measures included standardised autism diagnostic interviews (with parents) and tests of IQ, social cognition, theory of mind and attention (with children). RESULTS: The disruptive children possessed poorer pragmatic language skills (P<0.0001) and mentalising abilities (P<0.05) than comparisons. Nine disruptive children (35%) met ICD-10 criteria for atypical autism or Asperger syndrome. CONCLUSIONS: Many persistently disruptive children have undetected disorders of social communication, which are of potential aetiological significance.

Functional dissociation of amygdala-modulated arousal and cognitive appraisal, in Turner syndrome.

The amygdala is preferentially activated by facial expressions of fear. Right and left amygdala are hypothesized to play distinct, but complementary, roles that influence somatic and cognitive responses to facial expressions. Right amygdala activation is linked to autonomic arousal, and thus indirectly influences left hemisphere cognitive processing centres. Left amygdala activation is more closely associated with cognitive processing and differentiation of facial emotions. A double-dissociation between the functions of left and right amygdala is implied by lesion studies but supportive evidence is inconsistent, partly because patients with structural anteromedial temporal anomalies have experienced variable surgical procedures. A functional dissociation can be demonstrated between arousal and the cognitive appraisal of fearful faces in the condition of X-monosomy or Turner syndrome. Previous research found Turner syndrome women of normal verbal intelligence are seriously impaired in their ability cognitively to differentiate fearful from other facial expressions but they acquire fear conditioning normally, with enhanced autonomic responses. These findings supported the dissociation hypothesis, which was formally tested in a study of 12 X-monosomic and 12 control females who participated in functional magnetic resonance imaging during which simultaneous skin conductance recordings were acquired. Faces depicting fear or neutral emotions were presented to both case and control subjects in random order. Arousal to (fearful-neutral) faces was associated with transiently increased skin conductance responses and bilateral amygdala activation in both groups, but X-monosomic females had proportionately greater--and more persistent--right amygdala activation than controls. In both groups, cognitive accuracy correlated positively with differential activity of left fusiform gyrus. There was a significant correlation between the left fusiform and left medial amygdala activation only in normal females, and only in them did differential SCRs (to fearful-neutral faces) correlate positively with left fusiform responses. Arousal and cognitive appraisal functions of the amygdala can thus be functionally dissociated. X-monosomy selectively impairs explicit recognition of fearful faces in the presence of normal or enhanced autonomic reactivity, and is associated with a functional dissociation of activity in left amygdala and left fusiform gyrus. These findings imply X-linked genes are essential for binding somatic responses to the cognitive appraisal of emotional stimuli.

Social communication deficits in conduct disorder: a clinical and community survey.

BACKGROUND: Increasing numbers of children are referred to Child and Adolescent Mental Health Services because of disruptive behaviour. Recent reviews on the origins of conduct problems indicate that the most severe and persistent forms are found predominantly among males with a range of neurodevelopmental vulnerabilities, which are likely to have biological substrates. In this study, we tested the hypothesis that many children who are identified with conduct disorder actually have a primary deficit in pragmatic language skills, of a quality and degree that is similar to children on the autistic spectrum. We hypothesised that pragmatic difficulties may underlie the antisocial behaviour in a proportion of children who are labelled as conduct disordered. METHODS: Using the Children's Communication Checklist (Bishop, 1998), we surveyed 142 children who had been referred for clinical investigation, with a predominant diagnosis of either an autistic spectrum condition (n = 87) or conduct disorder (n = 55), and 60 typically developing comparison children. Among children with conduct disorders, males predominated 9:1. RESULTS: On the basis of parent and teacher ratings, two-thirds of those with conduct disorders had pragmatic language impairments and other behavioural features similar in nature and degree to those of children with autism, independent of IQ. In a further study, we surveyed 54 children who had been excluded from elementary schools in a socio-economically disadvantaged inner-London borough and found over two-thirds to have comparable deficits. CONCLUSIONS: These findings have both theoretical and practical implications. First, they indicate the presence of communicative problems in a sub-group of children in whom conduct rather than language had been the major concern. Second, they indicate that severe deficits in pragmatic abilities and autistic-like behaviours can coexist with psychiatric conditions other than autism, especially in boys. Third, they imply that the management of many disruptive children could profitably be addressed to ameliorating their social and communicative skill deficits.

Individual differences in cognitive planning on the Tower of Hanoi task: neuropsychological maturity or measurement error?

The Tower of Hanoi (ToH) task was given to 238 children aged from 7 to 15 years, and 20 adults. Individual variation within an age band was substantial. ToH score did not correlate significantly with Verbal IQ, nor with ability to inhibit a prepotent response. We readministered the ToH to 45 children after 30 to 40 days. The test-retest correlation of .5 is low in relation to accepted psychometric standards, though at least as high as reliability of the related Tower of London (ToL) in adults. The reasons for low reliability remain unclear: task novelty did not seem to be involved, as children did not improve on retest. We conclude that it is not safe to use this test to index integrity or maturation of underlying neurological systems in children. We compared our results with three published studies using the ToL with children, and found similar levels of performance on problems involving the same number of moves. Another study using automated ToL obtained much poorer scores, suggesting that computerised presentation may impair children's performance.

Seven ring (X) chromosomes lacking the XIST locus, six with an unexpectedly mild phenotype.

Small ring (X) chromosomes lacking the XIST gene at Xq13.2 have been associated with a severe phenotype that includes mental retardation, facial dysmorphism and congenital abnormalities. It has been hypothesised that the loss of XIST results in functional disomy for the sequences contained in the ring. We studied 47 females with a 45,X/46,r(X) karyotype and found seven to have an XIST-negative ring. Only one of the seven patients had the severe phenotype. The remaining six patients had physical phenotypes consistent with Turner syndrome. The rings were characterised cytogenetically and molecularly. The severe phenotype in one patient can be explained by the absence of XIST expression, the relatively large amount of Xp material in the ring and, possibly, the concomitant maternal uniparental isodisomy. We propose three explanations for the unexpectedly mild phenotypes in the remaining six patients; (1) the rings contained limited amounts of X-chromosome material, and sequences that, when functionally disomic, result in a severe phenotype were absent; (2) mosaicism resulting in the absence of the ring from tissues, such as the brain, which are important in the severe phenotype and (3) the presence of an inactive X in some tissues at some time, exemplified by the demonstration of XIST expression in one patient.

Behavioural neuroscience and child psychopathology: insights from model systems.

We have just emerged from "the Decade of the Brain", yet in so many ways it was the "Decade of the Genome". What relevance does the remarkable advance in knowledge in genetics and neuroscience over that period have to our understanding of child psychopathology? When the complexity of the genetic systems involved in behavioural regulation of relatively simple organisms such as the nematode worm Caenorhabditis elegans or the fruitfly Drosophila melanogaster is considered, the possibility of comprehending the links from genes to behaviour in the developing child seems remote. Yet, the principles of investigation in model systems are not so different to those that should apply in humans. This review draws out the parallels, and introduces recent findings from behavioural studies of C. elegans, D. melanogaster, and the laboratory mouse, as well as humans, to illustrate the point.

Distinctive patterns of memory function in subgroups of females with Turner syndrome: evidence for imprinted loci on the X-chromosome affecting neurodevelopment.

X-monosomy is a form of Turner syndrome (TS) in which an entire X chromosome is missing. It is usually assumed that neuropsychological deficits in females with TS result from insufficient dosage of gene products from alleles on the sex chromosomes. If so, then parental origin of the single X chromosome should be immaterial. However, if there are imprinted genes on the X chromosome affecting brain development, neuropsychological development will depend on the parental origin of the single X chromosome. We contrasted verbal and visuospatial memory in females with a single paternal X chromosome (45,X(p)) and those with a single maternal X (45,X(m)). Neither group showed any impairment on immediate story recall; if anything, performance was above control levels. Groups did not differ on a measure of delayed recall. However, when delayed recall was considered after adjusting for level of immediate recall, 45,X(m) females showed enhanced verbal forgetting relative to controls over a delay. On the Rey figure, both groups were poor at copying the figure, but, after adjusting scores for initial copy score and strategy, only the 45,X(p) females showed disproportionate forgetting relative to controls. We propose there may be one or more imprinted genes on the X chromosome that affect the development of lateralised brain regions important for memory function.

Imprinting, the X-chromosome, and the male brain: explaining sex differences in the liability to autism.

Males are at least four times more likely to develop autism than females. Among relatives with a broader autistic phenotype, males predominate too. Autism is a highly heritable disorder, yet genome scans have not revealed any predisposing loci on the sex chromosomes. A nongenetic explanation for male vulnerability, such as exposure to prenatal androgens, is unlikely for a variety of reasons. A novel genetic mechanism that resolves many of the outstanding difficulties is outlined here. The imprinted-X liability threshold model hypothesizes that the threshold for phenotypic expression of many autistic characteristics is influenced by an imprinted X-linked gene(s) that is protective in nature. Imprinted genes are known to play an important role in normal fetal and behavioral development. The gene is expressed only on the X-chromosome that is inherited from the father and raises the threshold for phenotypic expression. It is normally silenced when transmitted maternally. Because only females have a paternal X-chromosome, the threshold for phenotypic expression is higher in them than in males. Evidence for the existence of the genetic locus was found in a study of females with X-monosomy (Turner's syndrome) in which females had either a single paternal or maternal X-chromosome. Identifying the sites of action of this X-linked gene could lead to the discovery of autosomal loci that confer more directly a predisposition to autism.

Genomic imprinting of the X chromosome: a novel mechanism for the evolution of sexual dimorphism.

Genomic imprinting is the differential marking of maternally and paternally inherited alleles of specific genes or chromosome regions during gametogenesis. The imprint silences the allele from 1 parent. A number of imprinted genes that are expressed in the brain have been identified in humans. They control the actions of other genes or regulate their products. Sexual dimorphism in the vertebrate brain is conventionally thought to be due to the epigenetic action of gonadal hormones. Sex differences could also reflect the actions of an imprinted X-linked locus. Until very recently no imprinted gene had been described on the X chromosome in humans. Here the implications of such a mechanism for the evolution of sexual dimorphism are discussed.

A molecular and FISH analysis of structurally abnormal Y chromosomes in patients with Turner syndrome.

Fourteen patients with Turner syndrome and a structurally abnormal Y chromosome were analysed by PCR amplification and fluorescence in situ hybridisation for the presence of sequences specific to defined regions of the Y chromosome. Thirteen patients had a mosaic karyotype including a 45,X cell line and one case was non-mosaic in cultured lymphocytes. Ten patients had a pseudodicentric Yp chromosome, two an isodicentric Yq, one a pseudodicentric Yq, and one a derived Y chromosome. Two of the patients with a psu dic(Yp) chromosome had complex karyotypes with more than two cell lines, one of which exhibited five morphologically distinct mar(Y) chromosomes, presumably derived from a progenitor psu dic(Yp). Nine of the ten psu dic(Yp) chromosomes were positive for all Yp and Yq probes used except DYZ1 which maps to Yq12, suggesting a common breakpoint near the Yq euchromatin/heterochromatin boundary. In the three patients with a dicentric Yq chromosome two different breakpoints were observed; in two it was between PABY and the subtelomeric repeat sequence and in one it was between DYZ5 and AMGY in proximal Yp. Our results suggest that the great majority of structurally abnormal Y chromosomes found in Turner syndrome mosaics contain two copies of virtually all of the functional Y chromosome euchromatin.

Oral-motor dysfunction in children who fail to thrive: organic or non-organic?

Forty-seven children with non-organic failure to thrive (NOFT) were identified from a whole-population survey of children's growth and development. A significant proportion (N=17) of these 47 children were found to have oral-motor dysfunction (OMD) identified using a previously validated assessment tool. NOFT children with OMD and those with normal oral-motor function (N=30) were compared in order to ascertain whether there were any neurodevelopmental differences which might explain this finding. We hypothesized that children with OMD might have a subtle neurodevelopmental disorder. Few psychosocial variables discriminated the two groups. However, cognitive stimulation within the home and cognitive-growth fostering during mealtimes was much poorer for children with OMD. Some evidence has suggested that NOFT children with OMD may be 'biologically' more vulnerable from birth. We suggest that the continued use of the term 'non-organic' to describe failure to thrive in such children is questionable and requires redefining.

A study of females with deletions of the short arm of the X chromosome.

We have undertaken a clinical and molecular study of 25 females with deletions of the short arm of the X chromosome. We have determined the deletion breakpoints, the parental origin and the activation status of the deleted X chromosomes. Genotype-phenotype correlations suggest that the presence of a single copy of the DFFRX gene, previously postulated as a gene involved in the ovarian failure seen in Turner syndrome, may be compatible with normal ovarian function, and that there may be a gene for Turner-like features located in distal Xp22.3.

Metaphyseal growth arrest lines in psychosocial short stature.

Metaphyseal growth arrest lines are seen in children who experience significant physical stress such as infection or malnutrition over a sufficient period of time. These lines have not been reported previously in children with psychosocial short stature (PSS). Two boys and a girl with PSS with metaphyseal growth arrest lines on skeletal radiographs at the time of maximal stress in their homes are described. All three had reversible growth hormone insufficiency during admission, which is pathognomic for PSS. Multiple growth arrest lines in the distal end of the radius or vertebrae should alert clinicians to an alternative diagnosis in a child with growth hormone insufficiency. This may provide a clue to the diagnosis of occult PSS.

Genetic factors in the etiology of child psychiatric disorders.

This review discusses recent advances in our understanding of the genetic basis of child psychiatric disorders. As in adult psychiatry, progress in this area has been slow. First, it now appears clearer than ever that the "one gene, one disease" model is inappropriate for the vast majority of psychiatric disorders. Second, considerable resources are still being devoted to the search for genes, done using linkage and association models, together with twin and adoption studies, on the basis of case recognition according to conventional disease classification. Recent progress with conventionally specified disorders is reviewed and contrasted with the remarkable advances being made in the identification of the genetic basis of key cognitive processes through the power of modern molecular genetic techniques. Child psychiatric genetic could profit from a new focus on the search for the genetic processes underlying specific cognitive functions that, in turn, underpin child psychiatric disorders, especially those that are neurodevelopmental in origin.

Evidence from Turner's syndrome of an imprinted X-linked locus affecting cognitive function.

Turner's syndrome is a sporadic disorder of human females in which all or part of one X chromosome is deleted. Intelligence is usually normal but social adjustment problems are common. Here we report a study of 80 females with Turner's syndrome and a single X chromosome, in 55 of which the X was maternally derived (45,X[m]) and in 25 it was of paternal origin (45,X[p]). Members of the 45,X[p] group were significantly better adjusted, with superior verbal and higher-order executive function skills, which mediate social interactions. Our observations suggest that there is a genetic locus for social cognition, which is imprinted and is not expressed from the maternally derived X chromosome. Neuropsychological and molecular investigations of eight females with partial deletions of the short arm of the X chromosome indicate that the putative imprinted locus escapes X-inactivation, and probably lies on Xq or close to the centromere on Xp. If expressed only from the X chromosome of paternal origin, the existence of this locus could explain why 46,XY males (whose single X chromosome is maternal) are more vulnerable to developmental disorders of language and social cognition, such as autism, than are 46,XX females.

Failure to thrive and the risk of child abuse: a prospective population survey.

OBJECTIVE: To identify the relative importance of failure to thrive during infancy as a risk factor for later abuse or neglect. DESIGN: Whole population birth cohort (1 January to 31 December 1986) studied prospectively over a four year period. SETTING: An inner city health district in London, England. SUBJECTS: 2609 births, of whom 47 were identified as having non-organic failure to thrive by first birthday. MAIN OUTCOME MEASURES: Registration on Child Protection Register, or subject to investigation of suspected abuse or neglect without registration. RESULTS: 2.5% (64) of birth cohort had been placed on the Child Protection Register during the period 1986-1990, and a further 1.2% (32) had been a cause for concern. The relative risk attributable to non-organic failure to thrive was 4.3 (95% CI 1.65 to 11.94) and exceeded other measured risk factors, including birth weight < 2500 g, 1.96 (95% CI 1.01 to 3.82); gestation < 35 weeks, 3.26 (95% CI 1.32 to 3.75); ordinal position > or = 4, 1.53 (95% CI 0.72 to 3.23). A multiple logistic regression confirmed the independent contribution of non-organic failure to thrive to subsequent poor parenting warranting professional intervention. CONCLUSIONS: Early postnatal non-organic failure to thrive is a risk factor for later serious parenting deficiencies, but previous research has overstated its importance. Within the community studied the nature of subsequent risk was (non-nutritional) neglect, rather than non-accidental injury. More than eight out of 10 cases do not give further cause for concern.