Atypical developmental trajectory of functionally significant cortical areas in children with chromosome 22q11.2 deletion syndrome

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder associated with neurocognitive impairments. This article focuses on the cortical gyrification changes that are associated with the genetic disorder in 6-15-year-old children with 22q11.2DS, when compared with a group of age-matched typically developing (TD) children. Local gyrification index (lGI; Schaer et al. [2008]: IEEE Trans Med Imaging 27:161-170) was used to characterize the cortical gyrification at each vertex of the pial surface. Vertex-wise statistical analysis of lGI differences between the two groups revealed cortical areas of significant reduction in cortical gyrification in children with 22q11.2DS, which were mainly distributed along the medial aspect of each hemisphere. To gain further insight into the developmental trajectory of the cortical gyrification, we examined age as a factor in lGI changes over the 6-15 years of development, within and across the two groups of children. Our primary results pertaining to the developmental trajectory of cortical gyrification revealed cortical regions where the change in lGI over the 6-15 years of age was significantly modulated by diagnosis, implying an atypical development of cortical gyrification in children with 22q11.2DS, when compared with the TD children. Significantly, these cortical areas included parietal structures that are associated, in typical individuals, with visuospatial, attentional, and numerical cognition tasks in which children with 22q11.2DS show impairments.     

Motor development in school-aged children with 22q11 deletion (velocardiofacial/DiGeorge syndrome)

The aim of this study was to compare the motor development of primary school children (age 5-14y) with a 22q11 deletion (del22q11) group and a control group. The effects of a congenital heart defect (CHD) and IQ on motor development were additionally studied within the del22q11 group. Motor development of 37 children with a del22q11 (20 males, 17 females; mean age 9y 4mo, range 5y 9mo-13y 3mo) and 34 controls (23 males, 11 females; mean age 9y 1mo, range 4y 8mo-13y 6mo) was assessed with the Bruininks-Oseretsky Test of Motor Proficiency. The del22q11 group showed a significant deficit in motor functioning compared with the control group (p < 0.01). Within the del22q11 group there was a significant effect of IQ on motor performance, but no effect of CHD was found. To conclude, primary school children with a del22q11 syndrome showed a significant deficit in motor performance compared with a control group. A significant effect of IQ on motor performance in del22q11 was found.     

Short-term memory and vocabulary development in children with Down syndrome and children with specific language impairment

A longitudinal comparison was made between development of verbal and visuo-spatial short-term memory and vocabulary in children with Down syndrome (DS), children with specific language impairment (SLI), and typically developing children as a control group. Participants were 12 children with DS (6 males, 6 females; mean chronological age 9y 9mo [SD 2.8 mo], range 8y 6mo to 11y 4mo); nine children with SLI (4 males, 5 females; mean chronological age 3y 9mo [SD 4.8mo], range 3y 3mo to 4y 5mo); and 12 typically developing children (5 males, 7 females; mean chronological age 4y 4mo [SD 3.9mo], range 3y 3mo to 4y 3mo). Participants were matched on mental age (mean mental age 4y 3mo). All participants completed verbal short-term memory, visuo-spatial short-term memory, and expressive and receptive vocabulary tasks on three occasions over 1 year. Similarities were seen in the clinical groups for verbal short-term memory. There was some evidence of difficulty in visuo-spatial short-term memory in the children with SLI relative to the other groups, but all three groups showed overlap in visuo-spatial short-term memory performance. At the final time-point vocabulary performance in the clinical groups was similar; the typically developing children showed higher vocabulary abilities than both clinical groups.     

Increased visual cortex glucose metabolism contralateral to angioma in children with Sturge-Weber syndrome

Functional reorganization after focal brain injury can lead to altered cerebral metabolism of glucose. Sturge-Weber syndrome (SWS) with unilateral involvement is a clinical model for evaluating the effects of early focal brain injury on brain metabolism and function. In this study, 2-deoxy-2[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) was used to measure glucose metabolism in cortex and basal ganglia, both ipsilateral and contralateral to the angioma, in 17 children (eight males, nine females; age range 1y 8mo-10y 4mo; mean 5y 7mo [SD 2y 11mo]) with unilateral SWS and epilepsy. The PET findings were compared with those of a control group of 11 age-matched children (four males, seven females; age range 3y-10y 8mo; mean 6y [SD 2y 10mo]) with partial epilepsy but normal magnetic resonance imaging and PET scans. In the SWS group, visual and parietal cortex showed decreased glucose metabolism on the side of the angioma (p=0.001) but increased metabolism on the contralateral side (p=0.002). In particular, glucose metabolism was very high in contralateral visual cortex of childrenwith SWS, showing severe occipital hypometabolism on the side of the angioma. Eight children with visual field defect showed increased metabolism in the contralateral visual cortex (p=0.012). These findings indicate that early, severe unilateral cortical damage in SWS may induce increased glucose metabolism in the contralateral visual cortex, probably reflecting reorganization.     

Neuromotor development in nocturnal enuresis

In children with nocturnal enuresis, a higher rate of minor neurological dysfunction has been found. The aim of this study was to assess timed performance (a measure of motor performance speed) and associated movements using a standardized and reliable instrument. The motor function of 37 children with nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age range 8y-14y 8mo) and 40 comparison children without enuresis (17 males, 23 females; mean age 10y 7mo [SD 1y 6mo]; age range 8y-14y 8mo) was assessed using the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a slower motor performance than comparison children, particularly for repetitive hand and finger movements. This study provides evidence for a maturational deficit in motor performance in children with nocturnal enuresis. In addition to a maturational deficit of the brainstem, it is proposed that there is a possible maturational deficit of the motor cortex circuitry and related cortical areas in children with nocturnal enuresis.     

Evidence from two genetic syndromes for the independence of spatial and visual working memory

This study aimed at investigating the possible dissociation between visual-object and visual-spatial working memory (WM) in individuals with Williams syndrome (WS) and Down syndrome (DS). Four study groups were included: WS group (10 males, 5 females) with a mean chronological age (CA) of 19 years 8 months (SD 6y 1mo) and a mean mental age (MA)of 6 years 11 months (SD 1y 5mo); WS comparison group (7 males, 8 females) comprised of typically developing children with a mean CA of 6 years 10 months (SD 10mo) and a mean MA of 6 years 11 months (SD 8mo)matched as a group with the participants with WS on the basis of mental age; DS group (11 males, 7 females) with a mean CA of 15 years 10 months (SD 5y 8mo) and a mean MA of 5 years 2 months (SD 8mo); and DS comparison group (10 males, 8 females) with a mean CA of 5 years and 1 month (SD 7mo)and a mean MA of 5 years 2 months (SD 8mo) selected to match the DS group on the basis of mental age. They were all administered tests that explored visual perception (Visual Perception Test - Subtest 4 and Line Orientation tests), visual imagery (imaging the colour of objects and the tail length of well-known animals), spatial imagery (mental rotation of visually presented or verbally evoked objects), and WM for visual-object and visual-spatial information. Individuals with WS exhibited specific difficulties in the visual-spatial, but not the visual-object, WM task. Instead, people with DS showed reduced performance in both tests. However, whereas the observed deficit in individuals with DS persisted when perceptual abilities were taken into account, the deficit in individuals with DS was compensated when their scores were adjusted for performance on perceptual tasks. These results support the hypothesis of a dissociation within the sketch-pad slave system in the WM model and reinforce the view of intellectual disability as a non-unitary condition.     

Hyperactive stretch reflexes, co-contraction, and muscle weakness in children with cerebral palsy

The aim of this study was to examine the repeatability of and relationships among spasticity, co-contraction of agonist–antagonist, and muscle strength in children with cerebral palsy (CP). Eight children with spastic diplegic CP (five males, three females; Gross Motor Function Classification System [GMFCS] Levels I–III; mean age 10y 2mo [SD 2y 9mo], range 6–13y) and nine children in a comparison group (six males, three females; mean age 8y 10mo [SD 2y 4mo], range 6y to 12y 6mo) were assessed twice to examine repeatability of Composite Spasticity Scale, soleus stretch reflexes, electromyography (EMG) co-contraction ratio, and torque recorded during maximal isometric voluntary contraction of ankle dorsiflexors and plantarflexors. Sixty-one children with spastic CP, (54 diplegic, seven hemiplegic; 32 males, 29 females; GMFCS levels I–III; mean age 10y 8mo [SD 2y 9mo], range 6–15y) were then assessed to delineate possible correlations among these measures. Intraclass correlation coefficients (0.78–0.97) showed high data repeatability in both groups. Children with spastic CP demonstrated significantly larger soleus stretch reflex/M-response areas smaller torques, but larger EMG co-contraction ratios during both voluntary dorsiflexion and plantarflexion (all p <0.05). Children with spastic CP who had larger soleus stretch reflex/M-response areas demonstrated larger plantarflexion co-contraction ratio ( r = 0.28), and produced smaller plantarflexion and dorsiflexion torques ( r = –0.48 and –0.27 respectively). However, no correlation was noted between soleus stretch reflex and clinical spasticity. Our findings demonstrated that hyperactive soleus stretch reflex affected torque production of ankle muscles. Moreover, the severity of spasticity may not be fully described by either stretch reflex or tone measure alone.     

Visual and spatial long-term memory: differential pattern of impairments in Williams and Down syndromes

This purpose of this study was to investigate visual-object and visual-spatial long-term memory (LTM) abilities in individuals with Williams syndrome (WS) and Down syndrome (DS). Four groups comprised of 15 participants were included: WS group (10 males) with a mean chronological age (CA) of 18 years 5 months, SD 6 years 4 months, and mean mental age (MA) of 6 years 8 months, SD 1 year 5 months; WS control group (eight males) comprised of typically developing children (CA mean 6y 7mo, SD 8mo); DS group, (10 males, CA mean 16y 5mo, SD 5y 10mo; MA mean 5y 4mo, SD 8mo); and DS control group (seven males) formed by typically developing children (CA mean 5y 6mo, SD 7mo). In the WS and DS groups mental age and IQ were evaluated with the Form L-M of the Stanford-Binet Intelligence Scale. Results showed that individuals with WS showed decreased learning of visual-spatial material but substantially typical learning of visual-object patterns as compared to a group of mental-age-matched typically developing children. Individuals with DS showed the opposite profile, i.e. typical learning of visual-spatial sequences but impaired learning of visual-object patterns. These results, showing an interesting double dissociation between these two genetic syndromes in the learning of visual-object patterns as opposed to visual-spatial data, support the interpretation of learning disability* as a heterogeneous condition, characterized by potentially very different qualitative profiles of cognitive impairment.     

Disabilities and cognition in children and adolescents with 22q11 deletion syndrome

The purpose of this study was to investigate cognitive and other disabilities in children and adolescents with 22q11 deletion syndrome. Thirty-three children (15 females, 18 males; age range 3 to 19y, median 7y 6mo) with 22q11 deletion were investigated for growth, development, neurology, cognition, motor function, and participation (measured as handicap**). Half of the children had never crawled, although they had shuffled, and commencement of walking was delayed (mean 18mo, SD 6mo). Hypotonia was found in 25 and poor balance in 24 of the 33 children; 17 out of 27 had definite motor problems, including two with spastic hemiplegia. Intelligence quotient (IQ) range was 50 to 100. Eleven patients had an IQ below 70, and 15 between 70 and 84. Verbal IQ was higher than Performance IQ. Level of handicap within the study group was considered moderate, and all but one child had extra support at school. We conclude that children with 22q11 deletion syndrome have multiple neurological, motor, and cognitive problems. Although the severity and number of problems varies, the combination of impairments and disabilities results in a low level of participation.     

Binding of visual and spatial short-term memory in Williams syndrome and moderate learning disability

A main aim of this study was to test the claim that individuals with Williams syndrome have selectively impaired memory for spatial as opposed to visual information. The performance of 16 individuals with Williams syndrome (six males, 10 females; mean age 18y 7mo [SD 7y 6mo], range 9y 1mo-30y 7mo) on tests of short-term memory for item and location information was compared with that shown by individuals with moderate learning difficulties (12 males, four females; mean age 10y 3mo [SD 1y], range 8y 6mo-11y 7mo) and typically developing children (six males, 10 females; mean age 6y 8mo [SD 7mo], range 5y 10mo-7y 9mo) of an equivalent level of visuospatial ability. A second aim was to determine whether individuals had impaired ability to 'bind' visual spatial information when required to recall 'item in location' information. In contrast to previous findings, there was no evidence that individuals with Williams syndrome were more impaired in the spatial than the visual memory condition. However, individuals with both Williams syndrome and moderate learning difficulties showed impaired memory for item in location information, suggesting that problems of binding may be generally associated with learning disability.     

Evidence of impaired neurocognitive functioning in school‐age children awaiting cardiac surgery

Aim Children with congenital heart disease (CHD) are at risk of developing neurocognitive problems. However, as these problems are usually identified after cardiac surgery, it is unclear whether they resulted from the surgery or whether they pre‐existed and hence might be explained by complications and events associated with the heart disease itself. The purpose of this study was to examine whether neurocognitive deficits commonly reported after cardiac surgery are present before surgery. Method Forty‐five children (22 males, 23 females; mean age 11y 6mo, SD 3y 0mo) with cyanotic and acyanotic heart diseases scheduled for elective cardiac surgery were compared with 41 healthy peers (17 males, 24 females; mean age 11y 10mo, SD 2y 10mo) for attention and processing speed, construction, motor speed, motor planning and fluency, and visual memory. Twenty‐three children in the patient group were awaiting their first cardiac surgery and 22 were awaiting follow‐up surgery. Results The patients showed manifest neurocognitive difficulties. Their performance was inferior to that of the healthy comparison group for motor planning (p=0.02) and visual memory (p=0.01). The same neurocognitive profile was found in the group of patients awaiting their first cardiac operation. Interpretation School‐age children with various forms of CHD are at risk of neurocognitive impairments before cardiac surgery.     

Increased gyrification in Williams syndrome: evidence using 3D MRI methods

Understanding patterns of gyrification in neurogenetic disorders helps to uncover the neurodevelopmental etiology underlying behavioral phenotypes. This is particularly true in Williams syndrome (WS), a condition caused by de novo deletion of approximately 1 to 2 Mb in the 7q11.23 region. Individuals with WS characteristically possess an unusual dissociation between deficits in visual-spatial ability and relative preservations in language, music, and social drive. A preliminary postmortem study reported anomalous gyri and sulci in individuals with WS. The present study examined gyrification patterns in 17 participants with WS (10 females, 7 males; mean age 28 years 11 months, SD 8 years 6 months) and 17 age- and sex-matched typically developing control participants (mean age 29 years 1 month, SD 8 years 1 month) using new automated techniques in MRI. Significantly increased cortical gyrification was found globally with abnormalities being more marked in the right parietal (p=0.0227), right occipital (p=0.0249), and left frontal (p=0.0086) regions. These results suggest that one or more genes in the 7q11.23 region are involved during the critical period when cortical folding occurs, and may be related to the hypothesized dorsal/ventral dissociation in this condition.     

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: a longitudinal study

The 22q11.2 deletion syndrome (22q11.2DS) is associated with very high rates of schizophrenia-like psychosis and cognitive deficits. Here we report the results of the first longitudinal study assessing brain development in individuals with 22q11.2DS. Twenty-nine children with 22q11.2DS and 29 age and gender matched controls were first assessed during childhood or early adolescence; Nineteen subjects with 22q11.2DS and 18 controls underwent follow-up during late adolescence-early adulthood. The 22q11.2DS subjects showed greater longitudinal increase in cranial and cerebellar white matter, superior temporal gyrus, and caudate nucleus volumes. They also had a more robust decrease in amygdala volume. Verbal IQ (VIQ) scores of the 22q11.2DS group that developed psychotic disorders declined significantly between assessments. Decline in VIQ in 22q11.2DS was associated with more robust reduction of left cortical grey matter volume. No volumetric differences were detected between psychotic and nonpsychotic subjects with 22q11.2DS. Brain maturation associated with verbal cognitive development in 22q11.2DS varies from that observed in healthy controls. Further longitudinal studies are likely to elucidate brain developmental trajectories in 22q11.2DS and their association to psychotic disorders and cognitive deficits in this population.     

Motor coordination, empathy, and social behaviour in school-aged children

Children with motor coordination problems are known to have emotional difficulties and poor social skills. The current study investigated whether children with poor motor ability have poor emotion recognition skills, and whether these could be linked to problems in social behaviour. It was hypothesized that difficulties in empathic ability might be related to the poor visuo-spatial processing ability identified in children with developmental coordination disorder (as defined by the American Psychiatric Association). The relationship between motor coordination, emotion recognition, and social behaviour was examined in a sample of 234 children (113 males, 121 females; mean age 9y 7mo, [SD 1y 8mo] age range 6y 8mo to 12y 11mo). From this sample two groups of 39 children each (17 females, 22 males), one group with motor difficulties (mean age 9y 11mo [SD 2y], range 6y 11mo to 12y 11mo) and the other of control children (mean age 10y [SD ly 11mo], range 6y 11mo to 12y 11mo), matched for age and sex, were compared using a set of six emotion recognition scales that measured both verbal and perceptual aspects of empathic ability. Children with motor difficulties were found to perform more poorly on scales measuring the ability to recognize static and changing facial expressions of emotion. This difference remained even when visuo-spatial processing was controlled. When controlling for emotion recognition and visuo-spatial organization, a child's motor ability remained a significant predictor of social behaviour.     

Psychosocial problems and seizure-related factors in children with epilepsy

In this study we describe psychosocial functions and seizure-related factors in a population-based sample of children with epilepsy. Psychosocial problems (Achenbach scales), cognitive function, and socioeconomic status were studied in 117 children with epilepsy aged between 6 and 13 years (mean age 11y [SD 2y 1mo] and 10y 8mo [SD 2y]; 71 males, 46 females) and in randomly selected controls matched with 117 children for sex and age (mean age 11y 2mo [SD 2y 1mo] and 10y 5mo [SD 2y 4mo]; 69 males, 48 females). The children had partial (n=67), generalized (n=43), or undetermined (n=7) epilepsy syndromes, and partial (n=68), generalized (n=47), or other (n=2) main seizure types. Psychosocial problems were more common among children with epilepsy than controls (odds ratio 5-9) and significantly related to epilepsy syndrome, main seizure type, age at onset, and seizure frequency. Mothers and teachers reported males with epilepsy as having more problems than females. Females self-reported psychosocial problems, males did not. Psychosocial problems were common in childhood epilepsy. Females appreciated the problems more realistically than males. Psychosocial problems should be considered an integral part of epilepsy management.     

Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

Aim  To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation.
Method  Saliva was collected from 61 healthy children (30 males, mean age 9y 5mo [SD 11mo]; 31 females, mean age 9y 6mo [1y 2mo]) and 100 children with CP who drooled (57 males, mean age 9y 5mo [3y 11mo], range 3–19y; 43 females, mean age 10y 1mo [4y 9mo], range 4–19y), of whom 53 had spastic, 42 had dyskinetic, and five had ataxic CP. Almost all children were affected bilaterally, and 90 of them were at Gross Motor Function Classification System levels III or higher. The saliva was collected by the swab saliva collection method. The intensity of drooling was evaluated using the drooling quotient.
Results  No difference was found in the flow rates, age, or sex between healthy children and children with CP who drooled. On additional subgroup analysis, the flow rates of children with dyskinetic CP differed statistically from those of healthy children (submandibular p =0.047, parotid p =0.040).
Interpretation  This study supports the finding in previous studies that no hypersalivation exists in children with CP who drool. Dysfunctional oral motor control seems to be responsible for saliva overflow from the mouth, whereas increased unstimulated salivary flow may occur in children with dyskinetic CP as a result of hyperkinetic oral movements.     

Executive functions and seizure-related factors in children with epilepsy in Western Norway

Executive functions (EFs), seizure-related factors, and school performance were studied in a population-based sample of children with epilepsy (n=117; 71 males, 46 females; mean age 10y 5mo [SD 2y]; range 6y-12y 11mo) and a comparison group (n=124; 71 males, 53 females; mean age 10y 1mo [SD 2y 1mo]; range 6y-12y 11mo). EF, cognitive function, depression, socioeconomic status, and school performance were examined. Patients with epilepsy performed significantly lower than the comparison group on all EF measures except incidental memory. Intellectual dysfunction and depression accounted for 43% of EF problems. All epilepsy syndrome groups (except Rolandic epilepsy) were associated with decreased EF in addition to early epilepsy onset, high seizure frequency, and polytherapy. Patients had more school performance problems than comparison children which were attributed partly to EF difficulties. All aspects of EF were affected in children with epilepsy and all epilepsy syndrome groups, except Rolandic epilepsy, influenced EF negatively. EF problems contributed to patients' school difficulties beyond intellectual dysfunction.     

Behavioral profiles of children with infantile nephropathic cystinosis

Children with infantile nephropathic cystinosis have evidence of visuospatial and arithmetic deficits on a background of normal intellectual and verbal skills. This study aimed to define further their behavioral phenotype. The Achenbach Child Behavior Checklist was completed by parents of: 64 children and adolescents with cystinosis (33 females, 31 males; mean age 8 y 8 mo, range 4 to 16y, SD 2 y 11 mo); 101 healthy controls (47 females, 54 males; mean age 8 y 4 mo, range 4 to 16 y, SD 2 y 11 mo); 21 children and adolescents with cystic fibrosis (CF), termed chronic-disease controls (9 females, 12 males; mean age 11 y 3 mo, age range 4 to 17 y, SD 3 y 5 mo). Compared with healthy controls, individuals with cystinosis had evidence of a significantly higher incidence of behavioral problems, including social problems, somatic complaints, and attention problems. Compared with the chronic-disease control group, the cystinosis group differed only on the Social Problems scale, with 22% of participants with cystinosis scoring in the 'at risk' range whereas no participant with CF received an elevated score on this scale. We conclude that children and adolescents with cystinosis have evidence of a significant incidence of social difficulties compared with individuals with another chronic illness and healthy participants. The combination of visuospatial problems, difficulty with arithmetic, attention problems, and social difficulties seen in the cystinosis group constitutes a behavioral phenotype of this genetic disorder. This cluster of cognitive and behavioral symptoms is also seen in the nonverbal learning disabilities syndrome, and suggests a possible early difference in brain development in children with cystinosis compared with children who do not share this genetic disorder.     

Functional performance of children with developmental coordination disorder at home and at school

This study investigated the functional performance of daily activities at home and at school in a population-based sample of children with different degrees of motor coordination impairment and competence. Sixteen children (seven males, nine females; mean age 8y, SD 9mo) with developmental coordination disorder (DCD), 25 with suspected DCD ([sDCD] 17 males, eight females; mean age 7y 6mo, SD 8mo), and 63 children without motor problems (39 males, 24 females; mean age 7y 9mo, SD 7mo) were recruited from public schools (Grades 1–3, age 6y 4mo–9y 10mo) using the Chinese version of the Developmental Coordination Disorder Questionnaire, the Movement Assessment Battery for Children, and the Bruininks-Oseretsky Test of Motor Proficiency. Functional performance was assessed using the Chinese versions of the Vineland Adaptive Behavior Scales and the School Function Assessment–Chinese version. The functional performance of children with DCD and sDCD was statistically significantly lower than those without DCD ( p's <0.05). χ² and logistic regression analyses showed significant differences among all groups in the proportion of children scoring at the 'inadequate' adaptive level of home performance ( p's <0.05). There were also significant differences among the groups in the proportion of children scoring below the cut-off in school performance ( p's <0.05). The findings show the pervasive impact of DCD on children's functional performance in daily activities at home and at school.     

Sex differences in tactile defensiveness in children with ADHD and their siblings

Tactile defensiveness (TD) is a disturbance in sensory processing and is observed in some children with attention-deficit-hyperactivity disorder (ADHD). TD has been examined in male children with ADHD and in children with ADHD without differentiating by sex. As males and females with ADHD may differ in the clinical expression of the disorder and associated deficits, the aim of this study was to examine sex differences in TD in males and females with ADHD. Non-affected siblings were also examined to investigate familiality of TD. The Touch Inventory for Elementary-School-Aged Children was administered to 47 children with ADHD (35 males, 12 females; mean age 9y 8mo [SD 1y 11mo]), 36 non-affected siblings (21 males, 15 females; mean age 8y 10mo [SD 2y 4mo]), and 35 control children (16 males, 19 females; mean age 9y 5mo [SD 6mo]). Results indicated that females with ADHD displayed higher levels of TD than males with ADHD (who did not differ from control males). This suggests that TD is sex specific and may contribute to the identification of ADHD in females, thus improving diagnostic and therapeutic strength in this under-referred group. Non-affected siblings were unimpaired, regardless of sex, which suggests that TD is specific to the disorder and not part of a familial risk for ADHD.