The behavioral profile of children aged 1-5 years with sex chromosome trisomy (47,XXX, 47,XXY, 47,XYY).

Children with SCT have an increased risk of suboptimal neurodevelopment. Previous studies have shown an elevated risk for neurobehavioral problems in individuals with SCT. However, not much is known about neurobehavioral problems in very young children; knowledge that could help with early identification of children at risk for suboptimal development, and that could help establish targets for early intervention. This study addressed the question of what the behavioral profile of children with SCT aged 1-5 years looks like. In total, 182 children aged 1-5 years participated in this study (NSCT =87, Nnonclinical controls = 95). Recruitment and assessment took place in the Netherlands and the United States. The SCT group was recruited through prospective follow-up (50%), information seeking parents (31%), and clinical referral (18%). Behavioral profiles were assessed with the child behavior checklist and the ages-and-stages social-emotional questionnaire. Levels of parent-rated problem behavior were higher in children with SCT. Difficulties with overall social-emotional functioning were already present in 1-year-olds, and elevated scores were persistent across the full age range. Affective and pervasive developmental behaviors were seen in late toddlerhood and prominent at preschool age. Anxiety, attention deficit, and oppositional defiant behaviors were seen in preschool-aged children. Within this cross-sectional study, the developmental trajectory of affective, pervasive developmental, and oppositional defiant behaviors seemed to be different for SCT children than nonclinical controls. Collectively, these results demonstrate the importance of behavioral screening for behavioral problems in routine clinical care for children with SCT from a young age. Social-emotional problems may require special attention, as these problems seem most prominent, showing increased risk across the full age range, and with these problems occurring regardless of the timing of diagnosis, and across all three SCT karyotypes.

Executive function in XXY: Comparison of performance-based measures and rating scales.

Few studies have systematically assessed executive functioning (EF) skills in boys with XXY, and these are limited by small samples and restricted EF assessment. This study used a broader battery of performance-based measures as well as parent-rating scales of EF in 77 boys and adolescents with XXY (mean age = 12.5 years), recruited from a clinical trial and an outpatient clinic. Exploratory factor analyses were used to create EF domains from performance-based measures, and similar domains were measured using the Behavior Rating Inventory of Executive Function and Conners Parent-Rating Scales. The boys with XXY showed a distinct EF profile, with the greatest deficit in attention and more moderate deficits in working memory, switching, and planning/problem solving. Parent ratings showed similar challenges, as well as impaired inhibition. Independent sample t-tests showed no difference on performance measures between boys diagnosed or not diagnosed with attention-deficit/hyperactivity disorder (ADHD), although parents of boys diagnosed with ADHD reported more difficulties. There were no differences on performance-based tests between those diagnosed pre- and postnatally, although parents of postnatally diagnosed boys reported more metacognitive problems. Language deficits, cognition, and socio-economic status did not account for EF deficits.

Adaptive functioning in children and adolescents with Trisomy X: An exploratory analysis.

Identifying the factors related to adaptive functioning will improve the information available to families and providers of females with Trisomy X. Cognitive and behavioral features were assessed in 50 females ages 12.2 ± 3.6 years using the Behavior Assessment System for Children Second Edition (BASC-2) and Wechsler Scales of Intelligence. Executive functioning, social skills, and autistic traits were evaluated in a subset. Adaptive functioning was assessed using the BASC-2 adaptive skills composite score (ASC). Participants were classified as average adaptive skills (ASC T-score > 40) or deficits (ASC T-score < 40). Group comparisons were conducted. Multiple linear regression examined which factors contributed to ASC score. Twenty-eight females (55.6%) had adaptive skills deficits with functional communication being the most commonly affected adaptive domain. The group with ASC in the average range had higher verbal IQ (VIQ) and lower rates of numerous behavioral concerns. Internalizing behavior composite, DSM-IV inattentive symptoms score, and VIQ were significant predictors of ASC. Prenatally diagnosed females comprised over 70% of those with average adaptive skills. In this study, internalizing behaviors, inattentive ADHD symptoms, and VIQ were associated with poorer adaptive functioning. Early interventions targeting internalizing behaviors, attention/executive functioning, and communication skills may improve adaptive skills and deserve further study.

The Association of Motor Skills and Adaptive Functioning in XXY/Klinefelter and XXYY Syndromes.

Aims: Klinefelter (XXY) and XXYY syndromes are genetic disorders in males characterized by additional sex chromosomes compared to the typical male karyotype of 46, XY. Both conditions have been previously associated with motor delays and motor skills deficits. We aimed to describe and compare motor skills in males with XXY and XXYY syndromes, and to analyze associations with age, cognitive abilities, and adaptive functioning. Methods: Sixty-four males with XXY and 46 males with XXYY, ages 4-20 were evaluated using the Beery Test of Visual Motor Integration and the Bruininks-Oseretsky Test of Motor Proficiency - 2nd Edition assessments, Vineland-2 adaptive scales, and cognitive testing. Results: Motor coordination impairments were found in 39% of the males with XXY and 73% of the males with XXYY. Both groups showed strengths in visual perceptual skills. Males with XXYY had lower mean scores compared to males with XXY across all assessments. Fine motor dexterity and coordination deficits were common. There was a positive correlation between VMI scores and adaptive functioning. Conclusion: Occupational and physical therapists should be aware of the motor phenotype in XXY and XXYY both to aid in diagnosis of unidentified cases and to guide intervention.

Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis.

Triple X syndrome (47, XXX) occurs in approximately 1:1,000 female births and has a variable phenotype of physical and psychological features. Prenatal diagnosis rates of 47, XXX are increasing due to non-invasive prenatal genetic testing. Previous studies suggest that prenatal diagnosed females have better neurodevelopmental outcomes. This cross-sectional study describes diagnosis, physical features, medical problems, and neurodevelopmental features in a large cohort of females with 47, XXX. Evaluation included review of medical and developmental history, physical exam, cognitive, and adaptive testing. Medical and developmental features were compared between the prenatal and postnatal diagnosis groups using rate calculations and Fisher's exact test. Cognitive and adaptive tests scores were compared using t-tests. Seventy-four females age 6 months-24 years (mean 8.3 years) participated. Forty-four (59.5%) females were in the prenatal diagnosis group. Mean age of postnatal diagnosis was 5.9 years; developmental delay was the most common indication for postnatal genetic testing. Common physical features included hypertelorism, epicanthal folds, clinodactyly, and hypotonia. Medical problems included dental disorders (44.4%), seizure disorders (16.2%), genitourinary malformations (12.2%). The prenatal diagnosis group had higher verbal (P < 0.001), general ability index (P = 0.004), and adaptive functioning scores (P < 0.001). Rates of ADHD (52.2% vs. 45.5%, P = 0.77) and learning disabilities (39.1% vs. 36.3%, P = 1.00) were similar between the two groups. These findings expand on the phenotypic features in females with Triple X syndrome and support that prenatally ascertained females have better cognitive and functional outcomes. However, prenatally diagnosed females are still at risk for neurodevelopmental disorders. Genetic counseling and treatment recommendations are summarized. © 2016 Wiley Periodicals, Inc.

"How should I tell my child?" Disclosing the diagnosis of sex chromosome aneuploidies.

To date, the disclosure of a sex chromosome aneuploidy (SCA) diagnosis to an affected individual has not been explored. This study aimed to assess the timing and content revealed to an affected child by his or her parent(s), resources accessed in preparation, parental feelings of preparedness, common parental concerns, and recommendations for disclosure approaches. Two online surveys were created: 1) for parents of a child with a diagnosis and 2) for individuals with a diagnosis. One-hundred thirty-nine parent surveys (XXY n = 68, XXX n = 21, XYY n = 9, other SCAs n = 41) and 67 individual surveys (XXY n = 58, XXX n = 9) were analyzed. Parents most frequently discussed the topics of learning disabilities (47 %) and genetics (45 %) with their child during the initial disclosure. A significantly greater proportion of parent respondents reported feeling prepared vs. unprepared for disclosure, regardless of their child's diagnosis (z-test of proportions, all p's < 0.001). Both prepared and unprepared parents most frequently accessed resources such as websites, support groups, and discussion with the child's physician prior to disclosure, with unprepared parents accessing fewer resources (M = 2.0 ± 1.41) than prepared parents [M = 2. ± 1.56; t(101) =-2.02, p < 0.05]. Common parental concerns included making the conversation age-appropriate, discussing infertility, and possible impact on the child's self-esteem. Both parent and individual respondents endorsed being honest with the child, disclosing the diagnosis early and before puberty, and discussing the diagnosis gradually over time. These results provide recommendations for parents, and suggest benefits from additional resources and supports to alleviate concerns when approaching diagnosis disclosure.

Early Social Behavior in Young Children with Sex Chromosome Trisomies (XXX, XXY, XYY): Profiles of Observed Social Interactions and Social Impairments Associated with Autism Spectrum Disorder (ASD).

Individuals with Sex Chromosome Trisomies (SCT; XXX, XXY, XYY) have an increased vulnerability for developing challenges in social adaptive functioning. The present study investigates social interaction behavior in the context of varying social load, and Autism Spectrum Disorder (ASD) symptomatology in young children aged 1-7.5 years old, with SCT (N = 105) and control children (N = 101). Children with SCT show less interaction behaviors and more social withdrawal, as compared to their control peers, which were most evident in the high social load condition. Second, social impairments related to ASD are more prevalent, as compared to controls (27.1% at clinical level). These findings stress the importance of early monitoring and (preventive) support of early social development in young children with SCT.

[Formula: see text] Emotional reactivity and expressivity in young children with sex chromosome trisomies: evidence from psychophysiological and observational data.

Although sex chromosomal trisomies (SCT) in children are highly prevalent and associated with an increased risk for neurodevelopmental difficulties including socio-emotional problems, little is known about underlying mechanisms that could drive this risk. Studying emotional reactivity and expressivity of young children with SCT in early childhood could identify deviations in early emotional development and potentially serve as risk markers to guide clinical care in developing interventions. Participants in the current study were 90 SCT children and 97 population-based controls, aged 1 to 7 years, who experienced a stress-inducing event in which physiological (heart rate) and observational data (expression of negative emotions) were collected. Results showed early disturbances in the emotion system of young children with SCT, in terms of blunted but prolonged emotional reactivity and a reduced emotional expressivity in response to stress. Further, the concordance between emotional reactivity (arousal response) and expressivity was significantly lower in SCT, compared to controls. Given the significant impact of emotions on adaptive day-to-day functioning, deviations in processing emotions could be an important underlying mechanism in explaining the heterogeneity and variability in developmental outcomes often described in individuals with SCT.

The impact of sex chromosome trisomies (XXX, XXY, XYY) on gaze towards faces and affect recognition: a cross-sectional eye tracking study.

BACKGROUND: About 1:650-1000 children are born with an extra X or Y chromosome (47,XXX; 47,XXY; 47,XYY), which results in a sex chromosome trisomy (SCT). This international cross-sectional study was designed to investigate gaze towards faces and affect recognition during early life of children with SCT, with the aim to find indicators for support and treatment. METHODS: A group of 101 children with SCT (aged 1-7 years old; Mage= 3.7 years) was included in this study, as well as a population-based sample of 98 children without SCT (Mage= 3.7). Eye gaze patterns to faces were measured using an eye tracking method that quantifies first fixations and fixation durations on eyes of static faces and fixation durations on eyes and faces in a dynamic paradigm (with two conditions: single face and multiple faces). Affect recognition was measured using the subtest Affect Recognition of the NEPSY-II neuropsychological test battery. Recruitment and assessment took place in the Netherlands and the USA. RESULTS: Eye tracking results reveal that children with SCT show lower proportion fixation duration on faces already from the age of 3 years, compared to children without SCT. Also, impairments in the clinical range for affect recognition were found (32.2% of the SCT group scored in the well below average range). CONCLUSIONS: These results highlight the importance to further explore the development of social cognitive skills of children with SCT in a longitudinal design, the monitoring of affect recognition skills, and the implementation of (preventive) interventions aiming to support the development of attention to social important information and affect recognition.

The spectrum of the behavioral phenotype in boys and adolescents 47,XXY (Klinefelter syndrome).

The behavioral phenotype of 47,XXY (Klinefelter syndrome) includes increased risks for developmental delays, language-based learning disabilities, executive dysfunction/ADHD, and socialemotional difficulties. However there is significant variability between individuals with 47,XXY, and many children and adolescents have minimal or no behavioral features while others have quite significant involvement. This paper describes behavioral features in a cohort of 57 children and adolescents with 47,XXY, including results on standardized measures of behavior (BASC-2), attention (Conner's Rating Scales), and social skills (Social Responsiveness Scale). A subset was directly assessed for autism spectrum disorders using the ADOS and ADIR. We discuss our results within the context of previous literature, including implications for genetic counseling, recommendations for care, and areas for future research.

Adaptive Skills in FXS: A Review of the Literature and Evaluation of the PEDI-Computer Adaptive Test (PEDI-CAT) to Measure Adaptive Skills.

As adaptive skills (AS) are dynamic and may indicate the success of an intervention, they are a common domain measured in clinical trials. Typical interview tools for measuring AS are time-consuming, and questionnaire measures often lead to inconsistent information. The present study was designed to evaluate the feasibility, validity and test-retest performance of the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) in Fragile X syndrome (FXS). The PEDI-CAT is administered via tablet and uses the item response theory to efficiently determine the items administered. The PEDI-CAT was administered to 42 individuals with FXS (27 males; 15 females) aged 1.6-50.9 years (M = 14.9; SD = 11.2), followed by the Vineland-3 (VABS-3) interview for comparison. Administration was efficient (M = 21.7 min; SD = 9.5; range 8-45 min; mode = 19). Males and females did not significantly differ on the PEDI-CAT domains, except for daily activities (t(40) = -2.22, p = 0.037). Floor effects were significant for both measures, although the PEDI-CAT showed more floor effects in the mobility (35.7%) and social-cognitive (50%) domains. PEDI-CAT daily activities, mobility, social-cognitive and responsibility domains were all significantly correlated with most of the VABS-3 domains (all rho > 0.5; p < 0.01). Test-rest of the PEDI-CAT was comparable to the VABS-3. Results suggest that the PEDI-CAT is efficient, and minimal training is needed to administer it; however, it lacks specificity and shares a high rate of floor effects with the VABS-3.

Evaluating Social Interactions Using the Autism Screening Instrument for Education Planning-3rd Edition (ASIEP-3): Interaction Assessment in Children and Adults with Fragile X Syndrome.

An efficient and direct measure of social interactions and autism symptoms is needed for fragile X syndrome (FXS) research and clinical care. The Autism Screening Instrument for Educational Planning-Third Edition (ASIEP-3) Interaction assessment is a brief standardized measure that quantifies social responses under different conditions. The feasibility and validity of the ASIEP-3 was evaluated in 26 males and 13 females with FXS, along with cognitive testing and behavior questionnaires. The videos were scored at 10-second intervals, and the observed behaviors were scored as an interaction, independent play, no response, or aggression. In total, 39/41 participants successfully completed the ASIEP-3 (age M = 14.4 ± 10.2), with a range of cognitive abilities (abbreviated IQ (ABIQ) M = 58.9 ± 17.3, median = 50), behaviors (Aberrant Behavior Checklist (ABC) Total M = 37.00 ± 27.3), and autism diagnoses (N = 22/39). Reliable administration was demonstrated by all team members. The mean coded behaviors included interaction (40.6%), independent play (36.8%), no response (21.1%), and aggressive behavior (<10%). The interaction score was negatively correlated with the Social Communication Questionnaire (SCQ) score (p = 0.037), and the profiles differed by autism spectrum disorder (ASD) diagnosis. The intraclass correlation coefficients (ICCs) ranged from 0.79 to 0.93 for master's level and above. Administration of the ASIEP-3 was feasible for FXS across sex, age, ability, and behavior ratings by a trained research team. Reliable scoring required advanced training in the assessment of social development and FXS experience. The scores correlated to ratings and diagnoses of ASD. The ASIEP-3 shows promise to reliably index social interactions in FXS.

Language across the Lifespan in Fragile X Syndrome: Characteristics and Considerations for Assessment.

While it is widely acknowledged that language development is delayed for the majority of individuals with fragile X syndrome (FXS), there has been limited research into how best to assess this area. This study aimed to deepen the understanding of standardized language assessment in FXS by addressing the three following objectives: (1) Examine the feasibility and validity of widely-used, standardized assessments in participants with FXS; (2) describe linguistic and cognitive profiles for a large sample of individuals with FXS; and (3) Compare results obtained from objective testing in clinic to those obtained using caregiver report. Results indicate that previous results indicating strong correlations between cognition and language results hold true across a wide range of ages as well as across multiple assessments, with an exception in very young children. Caregiver report tended to give lower estimates of language ability than what was found using an objectively administered assessment. Appropriate assessments remain difficult to find as a significant percentage of individuals scored at floor when scaled scores were calculated. Further, a sub-group of participants were coded for behavioral response to testing demands, the majority being able to complete a standardized assessment. These results speak to the need for assessments that provide a wider range of items so individuals can both achieve a valid score and demonstrate progress in their attainment of language skills.

Prepulse inhibition in fragile X syndrome: feasibility, reliability, and implications for treatment.

Pharmacological rescue of behavioral, cognitive and synaptic abnormalities in the animal models of fragile X syndrome (FXS) has prompted the initiation of clinical trials of targeted treatments in humans with this condition. Objective, well-validated outcome measures that are reflective of FXS deficits and can be modeled similarly in animal and human studies are urgently needed. A protocol measuring prepulse inhibition (PPI) of the startle reflex, including measures of test-retest stability, was evaluated in 61 individuals with the fragile X full mutation (40 males and 21 females; 19.18 +/- 7.18 years) and 63 age-matched normal controls (35 males and 28 females; 20.83 +/- 6.96 years) across two laboratory sites with identical equipment and protocols. Relative to controls, the fragile X group had PPI impairment of 26%, 22%, and 28% for 60, 120, and 240 ms prepulse interval trial types, respectively, P = 0.000002. PPI test-retest reliability in 29 of the participants was excellent for the 120 ms prepulse interval trials (intraclass correlations: FXS, 0.85; controls, 0.88, 0.89 overall). This study demonstrates the feasibility and reliability of PPI measurement in a developmentally disabled population and highlights its potential as an outcome measure to test the efficacy of targeted neurotherapeutic agents.

Amygdala dysfunction in men with the fragile X premutation.

Premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene are associated with autism spectrum disorder in childhood, premature ovarian failure, and the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS, and perhaps the other clinical presentations among carriers, are thought to be due to toxic gain-of-function of elevated levels of the expanded-repeat FMR1 mRNA. Previous structural MRI studies have implicated the amygdala as a potential site of dysfunction underlying social deficits and/or risk for FXTAS. As a preliminary investigation of this possible association, adult males with the premutation, and male controls matched for IQ, age and education, completed three protocols that probe amygdala and sympathetic function: (i) a functional MRI paradigm that measures brain response to fearful faces; (ii) a fear-potentiated startle paradigm that differentiates responses to fearful faces and fearful non-social images and (iii) measurement of skin conductance level during a brief social encounter. Compared with controls, men with the FMR1 premutation demonstrated diminished brain activation in the amygdala and several brain areas that mediate social cognition while viewing fearful faces. The reduced amygdala activation in the premutation group was significantly associated with self-report of psychological symptoms on the Symptom Checklist-90--Revised. These men also displayed a lack of startle potentiation while viewing fearful faces and showed reduced skin conductance response when greeting an unfamiliar experimenter in comparison with the control group. The current findings may be related to social cognition deficits reported previously in children and adults with the premutation. The aetiology for this dysfunction may be elevated FMR1 mRNA or reduced FMR1 protein that occurs in carriers with higher premutation CGG repeat alleles.

Brief report: aggression and stereotypic behavior in males with fragile X syndrome--moderating secondary genes in a "single gene" disorder.

Although fragile X syndrome (FXS) is a single gene disorder with a well-described phenotype, it is not known why some individuals develop more significant maladaptive behaviors such as aggression or autistic symptoms. Here, we studied two candidate genes known to affect mood and aggression, the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA-VNTR) polymorphisms, in 50 males with FXS ages 8-24 years. Mothers and fathers of participants reported the frequency and severity of aggressive/destructive, self-injurious, and stereotypic behaviors. Polymorphism genotypes were unrelated to age and IQ. Results showed a significant effect of 5-HTTLPR genotype on aggressive/destructive and stereotypic behavior; males with FXS who were homozygous for the high-transcribing long (L/L) genotype had the most aggressive and destructive behavior, and individuals homozygous for the short (S/S) genotype had the least aggression. Those with the L/L genotype also had the highest levels of stereotypic behavior. There was no effect of MAOA-VNTR on behavior; however those with the high-activity, 4-repeat genotype were more likely to be taking SSRI or SNRI medication. This preliminary study prompts consideration of secondary genes that may modify behavioral phenotype expression in neurodevelopmental disorders, even those with a single gene etiology such as FXS.

Autism Spectrum Disorder in Males with Sex Chromosome Aneuploidy: XXY/Klinefelter Syndrome, XYY, and XXYY.

OBJECTIVE: Neurodevelopmental concerns in males with sex chromosome aneuploidy (SCA) (XXY/Klinefelter syndrome, XYY, XXYY) include symptoms seen in autism spectrum disorder (ASD), such as language impairments and social difficulties. We aimed to: (1) evaluate ASD characteristics in research cohorts of SCA males under DSM-IV compared to DSM-5 criteria, and (2) analyze factors associated with ASD diagnoses in SCA. METHODS: Evaluation of participants with XXY/KS (n=20), XYY (n=57) and XXYY (n=21) included medical history, cognitive/adaptive testing, Social Communication Questionnaire, Social Responsiveness Scale, Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, and DSM ASD criteria. Clinical impressions of ASD diagnostic category using the ADOS and DSM-IV criteria were compared to ADOS-2 and DSM-5 criteria. T-tests compared cognitive, adaptive, SES and prenatal vs. postnatal diagnoses between ASD and no ASD groups. RESULTS: ASD rates in these research cohorts were 10% in XXY/KS, 38% in XYY, and 52% in XXYY using ADOS-2/DSM-5, and were not statistically different compared to DSM-IV criteria. In XYY and XXYY, the ASD group had lower verbal IQ and adaptive functioning compared to those without ASD. Many children without ASD still showed some social difficulties. CONCLUSION: ASD rates in males with SCA are higher than reported for the general population. Males with Y chromosome aneuploidy (XYY and XXYY) were 4.8 times more likely to have a diagnosis of ASD than the XXY/KS group, and 20 times more likely than males in the general population (1 in 42 males, CDC 2010). ASD should be considered when evaluating social difficulties in SCA. Studies of SCA and Y-chromosome genes may provide insight into male predominance in idiopathic ASD.

Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands.

A very high proportion of individuals with fragile X syndrome (FXS) (FMR1 full mutation, > 200 CGG repeats) experience clinically significant anxiety. Recent evidence suggests that adult fragile X premutation carriers (55-200 CGG repeats) also are at risk for anxiety disorders, and they demonstrate limbic system alterations mediated by FMRP and/or elevated FMR1 mRNA that may explain this heightened risk. However, less is known about psychiatric symptoms including anxiety among children and adolescents with the premutation. We completed structured DSM-IV based diagnostic interviews focused on current anxiety in 35 children, adolescents or young adults with the premutation (ages 5-23 years, M = 11.3 ± 4.3; 27 male; 20 probands and 15 non-probands) and 31 controls (ages 5-18 years, M = 9.9 ± 3.6; 22 males). Among premutation carriers, 70.6% met criteria for at least one anxiety disorder (most frequently generalized anxiety disorder, specific phobia, social phobia, or obsessive compulsive disorder), compared to 22.6% of controls and 9.8% of the general population in this age range. Premutation carriers with intellectual disability, male gender, and proband status were associated with the highest rates of anxiety disorders. However, non-probands did have higher rates of having any anxiety disorder (40.0%) compared to general population norms. Although the results implicate anxiety as a target of screening and intervention among youth with the premutation, larger studies of unselected samples from the population of premutation carriers are needed to confirm and specify the degree and extent of psychiatric disorders in this condition.

Emotion potentiated startle in fragile X syndrome.

Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, functional brain resonance imaging investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We investigated the relationship between social avoidance and emotion-potentiated startle, a probe of amygdala activation, in children and adolescents with FXS, developmental disability without FXS (DD), and typical development. Individuals with FXS or DD demonstrated significantly reduced potentiation to fearful faces than a typically developing control group (p < .05). However, among individuals with FXS, social avoidance correlated positively with fearful-face potentiation (p < .05). This suggests that general intellectual disability blunts amygdalar response, but differential amygdala responsiveness to social stimuli contributes to phenotypic variability among individuals with FXS.

Cognitive and medical features of chromosomal aneuploidy.

This chapter describes the physical characteristics, medical complications, and cognitive and psychological profiles that are associated with chromosomal aneuploidy conditions, a group of conditions in which individuals are born with one or more additional chromosome. Overall, chromosomal aneuploidy conditions occur in approximately 1 in 250 children. Information regarding autosomal disorders including trisomy 21 (Down syndrome), trisomy 13 (Patau syndrome), and trisomy 18 (Edward syndrome) are presented. Sex chromosome aneuploidy conditions such as Klinefelter syndrome (47,XXY), XYY, trisomy X, and Turner syndrome (45,X), in addition to less frequently occurring tetrasomy and pentasomy conditions are also covered. Treatment recommendations and suggestions for future research directions are discussed.