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D Skuse

Publications and source records attributed to D Skuse.

At least 19 recordsLinked to original sources
PubMed2006

The development of mental state attributions in women with X-monosomy, and the role of monoamine oxidase B in the sociocognitive phenotype.

We hypothesized that women with Turner syndrome (45,X) with a single X-chromosome inherited from their mother may show mentalizing deficits compared to women of normal karyotype with two X-chromosomes (46,X). Simple geometrical animation events (two triangles moving with apparent intention in relation to each other) which usually elicit mental-state descriptions in normally developing people, did not do so to the same extent in women with Turner syndrome. We then investigated the potential role in this deficit played by monoamine oxidase B enzymatic activity. MAO-B activity reflects central serotonergic activity, and by implication the functional integrity of neural circuits implicated in mentalizing. Platelet MAO-B was substantially reduced in Turner syndrome. However, contrary to prediction, in this (relatively small) sample there was no association between MAO-B enzymatic activity and mentalizing skills in participants with and without Turner syndrome.

Adult↗
PubMed2005

How should paediatric examiners be trained?

Analysis of both the content and process of examinations is central to planning the appropriate education and training of examiners in paediatric clinical examinations. This paper discusses the case for developing training, reviews the current literature, and suggests the desirable attributes of examiners and the components of a training programme. Potential areas of further research are also considered.

Education, Medical, Graduate↗
PubMed2001

Hyperphagic short stature and Prader--Willi syndrome: a comparison of behavioural phenotypes, genotypes and indices of stress.

BACKGROUND: The clinical features of hyperphagic short stature (HSS) include short stature secondary to growth hormone insufficiency, excessive appetite (hyperphagia) and mild learning disabilities. Affected children characteristically live in conditions of high psychosocial stress. Symptoms resolve when the child is removed from the stressful environment. Family studies indicate a genetic predisposition. AIMS: To compare the behavioural and stress profiles of HSS with those of Prader--Willi syndrome (PWS), and to test the hypothesis that the genetic locus that predisposes to HSS co-inherits with the PWS locus at 15q11--13. METHOD: Twenty-five children with HSS, mean age 9.1 (s.d. 3.8) years, 28% female, were compared with 30 children with PWS, mean age 8.8 (s.d. 2.8) years, 33% female. RESULTS: The clinical profiles were largely similar across the conditions, but no evidence was found in HSS of co-inheritance of the PWS critical region. CONCLUSIONS: Hyperphagic short stature is one of the very few behavioural diseases associated with a pathognomonic physiological abnormality. Investigations of the suggested genetic dysregulation, which is so sensitive to environmental influences, may well be of importance in a broader context.

Child↗
PubMed2000

A clinical, cytogenetic and molecular study of 47 females with r(X) chromosomes.

We studied 47 patients with a 45,X/46,X,r(X) karyotype to identify phenotypic differences between these patients and 45,X patients, and to determine whether these differences could be explained by the status of genes within the ring. Only 2 patients had the 'severe' r(X) phenotype, and both were consistent with this resulting from functional disomy of genes normally subject to X inactivation. A further 7 patients also carried active rings but these patients did not have a more severe phenotype than those whose rings were inactivated, probably because their rings were smaller and did not contain the (as yet unidentified) genes whose functional disomy is particularly damaging. Patients with a r(X) did not show clear physical differences when compared with a 45,X series, except for a possible reduction in the frequency of oedema in those whose r(X) had an Xq breakpoint distal to DXS128E, at Xq13.2. Thus some protection from oedema may be provided by the presence of two copies of Xq13.2.

Adolescent↗
PubMed2000

Ring-X chromosomes: their cognitive and behavioural phenotype.

We tested the cognitive abilities and educational attainments of 47 patients with a ring X chromosome, to evaluate the extent to which these variables correlated with failure of r(X) inactivation and with mosaicism. We found possession of a r(X) chromosome was associated with an increased risk of significant learning difficulties, and with associated behavioural maladjustment, compared with 45,X Turner females. Nearly a third had been educated outside mainstream schools. The proportion of cells in peripheral blood containing an inactivated r(X) chromosome was negatively correlated with nonverbal IQ. The parental origin of the normal chromosome did not appear to affect adjustment or abilities. In a minority of r(X) cases associated with mental retardation, there had been a failure to inactivate the ring, due to loss of the XIST locus. However, failure of X-inactivation was not necessarily associated with a severe phenotype. The degree of impairment in IQ depended on the size of the active ring, and hence was proportionate to the number of (as yet unidentified) genes whose functional disomy affected brain development and functioning.

Adolescent↗
PubMed2000

The developmental sequelae of nonorganic failure to thrive.

The developmental sequelae of infant failure to thrive (FTT) were examined in an unreferred group of 6-year-olds with a history of severe nonorganic growth retardation, sampled from a 1-year birth cohort in an inner-city area of South London. Children who failed to thrive in infancy (weight below the third centile for at least 3 months) and their pairwise matched comparisons were originally studied at 15 months, and 42 cases and 42 controls (89.5% of the sample) were followed up. At 6 years, previously growth-retarded children were considerably smaller than matched comparisons, in terms of body mass index (BMI), and height and weight for age Z scores. History of FTT explained substantial variance in weight and BMI at 6 years, with maternal height also contributing to variation in height for age. Child cognitive functioning at 6 years was examined using the McCarthy Scales: cases had more limited quantitative and memory skills than comparisons, but there was no intergroup variation in general cognitive performance. In contrast to analyses of physical development, failure to thrive did not account for cognitive functioning; maternal IQ was the sole significant predictor of performance on all indices of child cognitive abilities. At 15 months, earlier growth faltering was linked to limitations in mental development, but these findings were not confirmed by the follow-up data: the timing of FTT was not related to cognitive abilities at 6 years. Results correspond to past research indicating that nonorganic failure to thrive is associated with persistent limitations in physical stature. There was little evidence of cognitive disadvantage for case group children at school age, suggesting that the adverse effects of early malnutrition on cognitive functioning appear to diminish over time.

Age Factors↗
PubMed1999

Psychological disturbance and service provision in parentally bereaved children: prospective case-control study.

OBJECTIVES: To identify whether psychiatric disturbance in parentally bereaved children and surviving parents is related to service provision. DESIGN: Prospective case-control study. SETTING: Two adjacent outer London health authorities. PARTICIPANTS: 45 bereaved families with children aged 2 to 16 years. MAIN OUTCOME MEASURES: Psychological disturbance in parentally bereaved children and surviving parents, and statistical associations between sample characteristics and service provision. RESULTS: Parentally bereaved children and surviving parents showed higher than expected levels of psychiatric difficulties. Boys were more affected than girls, and bereaved mothers had more mental health difficulties than bereaved fathers. Levels of psychiatric disturbance in children were higher when parents showed probable psychiatric disorder. Service provision related to the age of the children and the manner of parental death. Children under 5 years of age were less likely to be offered services than older children even though their parents desired it. Children were significantly more likely to be offered services when the parent had committed suicide or when the death was expected. Children least likely to receive service support were those who were not in touch with services before parental death. CONCLUSIONS: Service provision was not significantly related to parental wishes or to level of psychiatric disturbance in parents or children. There is a role for general practitioners and primary care workers in identifying psychologically distressed surviving parents whose children may be psychiatrically disturbed, and referring them to appropriate services.

Adolescent↗
PubMed1999

Xp deletions associated with autism in three females.

We report eight females with small deletions of the short arm of the X chromosome, three of whom showed features of autism. Our results suggest that there may be a critical region for autism in females with Xp deletions between the pseudoautosomal boundary and DXS7103. We hypothesise that this effect might be due either to the loss of function of a specific gene within the deleted region or to functional nullisomy resulting from X inactivation of the normal X chromosome.

Autistic Disorder↗
PubMed1999

Quality of life in Turner syndrome is related to chromosomal constitution: implications for genetic counselling and management.

Issues of self-appraisal, friendships and academic attainments are uniquely salient for all adolescents. For girls with Turner syndrome, social problems and learning difficulties often become more serious at this time, yet may be unacknowledged by those responsible for paediatric care because their focus is on growth and sexual maturation. Data on the social and educational adjustment of 110 45,X (monosomic) females aged between 6 and 25 years is presented. Detailed information on the patients' precise karyotype was used to demonstrate systematic differences in adjustment between those whose single X chromosome was maternally derived and those in whom it was paternal. Implications for educational support and parental guidance are discussed.

Adolescent↗
PubMed1999

A case-comparison study of the characteristics of children with a short stature syndrome induced by stress (Hyperphagic Short Stature) and a consecutive series of unaffected "stressed" children.

Recently a type of growth failure (Hyperphagic Short Stature) has been described, in which there is potentially reversible severe impairment of growth hormone secretion, in association with excessively high levels of psychosocial stress. This condition is a variant of the disorder formerly known as Psychosocial Dwarfism. In the present study we compared children with Hyperphagic Short Stature (N = 25, aged 9.04 years+/-3.78, 72% male) and a closely matched sample with normal height, drawn from comparably stressful family circumstances (N = 25, aged 10.61+/-3.04, 60% male). Measures of the psychosocial environment, anthropometry, and developmental history from infancy were obtained. Many symptoms thought previously to be characteristics of psychosocial dwarfism were found to be nonspecific stress responses. Hypotonia (p < .05), enuresis/encopresis (p < .01), and sleep cycle disruption (p < .05) did differentiate the groups. Growth, appetite, and sleep are all influenced by hypothalamic nuclei, suggesting hypothalamic pathology could account for most of the clinical features of Hyperphagic Short Stature.

Appetite Regulation↗
PubMed1998

Risk factors for development of sexually abusive behaviour in sexually victimised adolescent boys: cross sectional study.

OBJECTIVE: To identify factors that may increase the risk of a sexually victimised adolescent boy developing sexually abusive behaviour. DESIGN: Sexually victimised boys who had sexually abused other children were compared with sexually victimised boys who had not done so. SETTING: Social services departments in south east England were invited to refer sexually abused and sexually abusing boys to a London postgraduate teaching hospital. SUBJECTS: 25 adolescent boys aged between 11 years and 15 years and 11 months. MAIN OUTCOME MEASURES: Adjusted odds ratios estimated from unconditional logistic regression. RESULTS: Unadjusted odds rations for witnessing (8.1) as well as experiencing (18.0) intrafamilial violence and discontinuity of care (7.2) discriminated boys who had sexually abused from others who were solely victims of sexual abuse. Only the adjusted odds ratios for witnessing intrafamilial violence (39.7) discriminated the two groups. CONCLUSIONS: The risk of adolescent boys who have been victims of sexual abuse engaging in sexually abusive behaviour towards other children is increased by life circumstances which may be unrelated directly to the original abusive experience, in particular exposure to a climate of intrafamilial violence. Our findings have implications for the management of boys found to have been sexually abused and raise important questions about the possibility of secondary prevention of subsequent abusive behaviour in those at greatest risk.

Adolescent↗
PubMed1998

Three patients with a 45,X/46,X,psu dic(Xp) karyotype.

Few cases of isochromosomes for the short arm of the X have been reported and all are dicentric with variable portions of the long arms interposed between the two centromeres. This paper reports three cases of complete short arm duplication of one X chromosome in unrelated female patients. All patients also have a 45,X cell line and present with some characteristic features of Turner syndrome. We used conventional cytogenetics, in situ hybridisation, and molecular genetics to describe all three structurally abnormal chromosomes and the parental origin of two of them. We briefly discuss the "inactivation enhancement" theory; however, any genotype-phenotype correlation is complicated by the presence of the 45,X cell line.

Adolescent↗
PubMed1998

Short normal children and environmental disadvantage: a longitudinal study of growth and cognitive development from 4 to 11 years.

The aim of this investigation was to follow up a sample of exceptionally short but medically healthy children, and a normal comparison group, previously studied at 4 years of age. They lived in an inner-city area which was, on objective criteria, seriously disadvantaged in socioeconomic terms. When first seen at 4 years, cases were significantly impaired in cognitive abilities relative to comparisons, although firstborns were much less severely affected. Of the original 46 cases, 45 were assessed again at 11 years. Most continued to live in the same geographical area. Case children remained exceptionally short, even when parental stature was taken into account, although a degree of catch-up had occurred. One third had special educational needs, and a similar proportion had been referred for speech therapy. Verbal and nonverbal cognitive skills of both case and comparison children had, on the whole, changed little and group differences persisted. In conclusion, short normal children from socioeconomically disadvantaged backgrounds are at high risk of educational failure at elementary school.

Analysis of Variance↗
PubMed1997

Turner syndrome: a cytogenetic and molecular study.

Two hundred and eleven patients with a clinical diagnosis of Turner syndrome were studied. We report (i) the cytogenetic results, (ii) the frequency of cryptic mosaicism and (iii) the parental age and the parental origin of the abnormality. We scored 100 cells from blood cultures and found 97 patients to have a 45,X constitution, 15 to be 45,X/46,XX or 45,X/47,XXX mosaics, 86 to have a structurally abnormal X and 13 to have a structurally abnormal Y chromosome. Molecular methods were used to look for cryptic X and Y chromosome mosaicism in patients with a 45,X constitution. Two cryptic X but no cryptic Y mosaics were detected. In 74% of the 45,X patients the X was maternal in origin. The i(Xq)s were approximately equally likely to involve the paternal or maternal chromosome, while the majority of deletions and rings and virtually all the abnormal Y chromosomes were paternal in origin. We suggest that the preponderance of paternal errors in Turner syndrome may result from the absence of pairing along the greater part of the XY bivalent during paternal mei I, which may make the sex chromosomes particularly susceptible to both structural and non-disjunctional errors during male gametogenesis.

Adolescent↗
PubMed1996

A new stress-related syndrome of growth failure and hyperphagia in children, associated with reversibility of growth-hormone insufficiency.

BACKGROUND: Growth failure without organic aetiology but associated with behavioural disturbance and psychosocial stress has been termed psychosocial short stature. This condition is not a valid diagnostic entity, but encompasses failure to thrive, stunting secondary to chronic malnutrition, and idiopathic hypopituitarism. Some children show spontaneous catch-up growth when removed from the source of stress, without further treatment, but until now precise definition of this subgroup for the purpose of clinical identification has not been possible. METHODS: Hospital-referred children with growth failure unrelated to organic pathology, who came from stressful homes, were compared with children of short-normal stature identified from an epidemiological survey (n = 31). Growth-hormone dynamics were studied in the hospital group by a combination of diurnal profiles and provocation tests. The tests were repeated after a hospital stay of 3 weeks away from familial stress. Standard behavioural measures were obtained from home and school. FINDINGS: In a distinctive subgroup (n = 29), growth-hormone insufficiency was associated with characteristic behavioural features, especially hyperphagia and polydipsia, and a normal body-mass index. When the children were removed from their stressful home circumstances, growth-hormone insufficiency spontaneously resolved only in formerly hyperphagic subjects. 74% of the non-hyperphagic cases (n = 23) were anorexic, with a low body-mass index and normal growth-hormone responses to provocation tests. INTERPRETATION: We present explicit behavioural and developmental criteria by which the novel syndrome of hyperphagic short stature may be recognised clinically. Such children have a capacity for spontaneous recovery of growth-hormone production on removal from or reduction of stress. Discriminant and predictive validity of the core symptoms are demonstrated. Preliminary familial studies indicate a possible genetic predisposition.

Adolescent↗