Parent- and teacher-report of attention-deficit/hyperactivity disorder (ADHD) symptoms were examined using problem behavior and DSM-IV symptom inventory questionnaires for 63 children with full mutation fragile X syndrome (FXS) and 56 children without disabilities matched on mental age (MA). Prevalence rates of ADHD symptoms varied depending on type of measure (problem behavior or DSM-IV criteria), subscale (ADHD-inattentive or ADHD-hyperactive), scoring method (continuous T-scores or categorical scores based on DSM-IV algorithm), and rater (parent or teacher). Overall, 54-59% of boys with FXS met diagnostic behavioral criteria for either ADHD-inattentive type only, ADHD-hyperactive type only, or ADHD-combined type based on parent or teacher report. Boys with FXS were rated as having clinically high scores or met diagnostic criteria at higher rates than expected for the general population and had higher raw scores than their MA-matched peers. Parent ratings of boys with FXS resulted in higher ADHD-inattentive type and ADHD-hyperactive type T-scores than teachers. Boys who were rated as meeting DSM-IV criteria were more likely to be taking psychotropic medication and to have younger mental ages. Parents were substantially more likely than teachers to rate boys as meeting DSM-IV criteria for ADHD-inattentive type, while teachers were only slightly more likely than parents to rate boys as meeting DSM-IV criteria for ADHD-hyperactive type. Teachers were more likely than parents to rate boys as meeting DSM-IV criteria for ADHD when boys had lower levels of FMRP.

The performance of 54 boys with fragile X syndrome (FXS), ages 7 to 13 years, was compared to that of a group of typically developing boys who were matched on mental age (MA) and ethnicity across multiple measures of executive function (EF). Boys with FXS varied in their ability to complete EF measures, with only 25.9% being able to complete a set-shifting task and 94.4% being able to complete a memory for word span task. When compared to the control group, and controlling for MA and maternal education, boys with FXS showed significant deficits in inhibition, working memory, cognitive flexibility/set-shifting, and planning. No group differences were observed in processing speed. Mental age significantly impacted performance on working memory, set-shifting, planning, and processing speed tasks for both groups. In boys with FXS, MA significantly predicted performance on working memory and set-shifting tasks. Our findings suggest that deficits in EF in boys with FXS are not solely attributable to developmental delays but, rather, present as a true array of neurocognitive deficits.

Sustained attention and response inhibition were examined in boys with full mutation fragile X syndrome (FXS) using adapted visual and auditory continuous performance tests (CPTs). Only 61% of 56 boys with visual CPT data and 54% of 52 boys with auditory data were able to demonstrate sufficient understanding to complete the visual and auditory CPTs, respectively. Mental age (MA) predicted whether boys with FXS were able to demonstrate understanding of the CPTs. The performance of boys with FXS who were able to complete the CPTs was compared to a sample of boys without disabilities matched on MA. Boys with FXS demonstrated similar or smaller declines in sustained attention over task time than their MA-matched peers on the visual and auditory CPTs, respectively, but consistently demonstrated greater declines in response inhibition over task time than their MA-matched peers. There were no differences between groups for response time of hits. Higher MAs consistently predicted better sustained attention and response inhibition over task time on the visual and auditory CPTs. Furthermore, boys taking psychotropic medication performed better at the beginning of most tasks, although their performance deteriorated at a faster rate over time, and boys rated as meeting diagnostic criteria for ADHD-hyperactive type had more difficulty over task time with response inhibition on the auditory CPT. For both boys with FXS and their MA matches, performance was better on the visual CPT than on the auditory CPT though this effect may be attributable to a number of factors other than the modality.

Down syndrome (DS) is the most common genetic cause of significant intellectual disability in humans. It was one of the first chromosomal disorders of humans to be associated with intellectual disabilities and, as such, has provided an evidence-based foundation from which work on many different disorders has been launched. John Langdon Down first described this syndrome in 1866 using the term mongoloid idiocy. The initial clinical description of DS comprised physical features (e.g., epicanthal folds, flat and broad face, enlarged tongue, microcephaly, short stature) and cognitive characteristics (e.g., intellectual impairment, fine and gross motor coordination problems, poor speech articulation). He also described a relatively positive personality in these individuals. Contemporary topographical descriptions are remarkably similar to Down’s description nearly 150 years ago, but a variety of other healthrelated issues have been uncovered since that time including congenital cardiac abnormalities, hypotonia, hearing and visual impairments, hypothyroidism, and precocious aging (Rasmussen, Whitehead, Collier, and Frias 2008). In accordance with the core tenets of this text, in this chapter we discuss epidemiology, etiology, and what is known about core pathophysiological mechanisms in DS; neurological abnormalities, including contemporary findings in neuroimaging; neurocognitive and socialbehavioral manifestations; and emergent evidencebased treatment efforts. The chapter concludes with a brief discussion of the phenotype-genotype linkages for DS, and a review of the priorities set by a national panel of experts in DS (Rasmussen et al. 2008). When compared to other congenital abnormalities, DS represents one of the most common disorders. Contemporary prevalence estimates indicate the occurrence of DS in approximately 9.0–11.8 (Shin et al. 2009) to 13.66 (Canfield et al. 2006) per 10,000 live births. The rate of infants born with DS also has a strong relationship with increasing maternal age. For example, a 20-year-old mother has a 1 in 1,923 chance of giving birth to an infant with Down syndrome, whereas the chance for a 49-year-old mother is 1 in 12 (Prescott 1988). The cause of this phenomenon, however, is not well understood (Lamb and Hassold 2004).