Objective-The 22q11 deletion syndrome is associated with a range of possible physical anomalies, probable ongoing learning disabilities, and a specific constellation of neuropsychological deficits, including impairments in selective and executive visual attention, working memory, and sensorimotor functioning. It has been estimated that 25% of the children with 22q11 deletion syndrome go on to develop schizophrenia in late adolescence or adulthood. This is of urgent concern. Specification of early brain network vulnerabilities may provide a basis for early intervention while indicating critical links between genes and severe psychiatric illness. Neuropsychological studies of children with 22q11 deletion syndrome have implicated an array of potentially aberrant brain pathways. This study was conducted to determine whether preattentive processing ("sensorimotor gating") deficits are present in this population.Method-The authors administered a test of prepulse inhibition to 25 children with 22q11 deletion syndrome and their 23 sibling comparison subjects, ages 6-13. It was predicted that the children with 22q11 deletion syndrome would have lower prepulse inhibition than the comparison subjects.Results-Prepulse inhibition in the children with 22q11 deletion syndrome (26.06%) was significantly less than that of the sibling comparison subjects (46.41%). Secondary analyses suggested that this decrement did not reflect developmental delay, and lower prepulse inhibition was associated with particular subsyndromal symptoms in some children.Conclusions-Sensorimotor gating is lower in children with 22q11 deletion syndrome. These findings may indicate specific brain circuits that are anomalous in 22q11 deletion syndrome.The 22q11 deletion syndrome results from a meiotic deletion of genetic material at the q11.2 site on chromosome 22. It occurs in 1 of every 6,000 births (1) and in over 90% of the cases is de novo (2). Associated congenital anomalies occur in some but not all children and may include heart defects, immunologic deficits, craniofacial dysmorphologies, velopharyngeal defects such as overt or submucous cleft palate, or inflammation-related pain syndromes (3). Before the identification of a single underlying deletion, the different clinical labels described a child's primary physical anomaly and included "conotruncal anomaly face syndrome" (heart defect with facial dysmorphologies), "velocardiofacial syndrome" (velopharyngeal, heart, and facial anomalies), and "DiGeorge syndrome" (immunologic insufficiency).Broadly speaking, the academic and neuropsychological profile of children with 22q11 deletion syndrome is more consistent than their physical phenotype. Gross motor, fine motor, and expressive language delays have been identified in the early years (4) and are followed by learning disabilities and academic failures, attention impairment, and behavioral anomalies in an estimated 90%-100% of the school-age children with this syndrome (5,6 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manu...

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.

The 22q11 chromosomal deletion syndrome (22q11 DS) is associated with learning disabilities and a complex neuropsychological profile. Previous findings have suggested that executive attention deficits might underlie other neurocognitive anomalies. We administered the child Attention Network Test (ANT) to 52 children ages 5.0 to 11.5, 32 22q11 DS children (19 girls) and 20 controls (13 girls) and assessed the efficiency of segregated executive, orienting, and alerting networks. We hypothesized that 22q11 DS children have impaired executive network efficiency as compared to control siblings. The internal validity of the child ANT was confirmed for this population. Analysis of variance results showed significant main effects for flanker and cue types and no interaction effect in either 22q11 DS children or control siblings. Compared to control siblings, 22q11 DS children had significantly larger (less efficient) executive network scores, significantly increased errors on only incongruent trials, and a significant correlation between executive network scores and accuracy. The implications of these findings for future neurocognitive studies of 22q11 DS children are considered.The 22q11 deletion syndrome (22q11 DS) results from a meiotic deletion of DNA at the q11.2 site on chromosome 22 and its estimated prevalence is 1:4,000 (du Montcel, Mendizabal, Ayme, Sevy, & Philip, 1996). In over 90% of cases the deletion is not transmitted (Morrow et al., 1995). Congenital anomalies of widely varying severity can be associated with this condition and might include heart defects, immunologic deficits, craniofacial dysmorphologies, and velopharyngeal defects such as overt or submucous cleft palate (e.g., Ryan et al., 1997). Prior to identification of a single associated deletion, different clinical labels were used to indicate a given child's congenital anomalies, including DiGeorge Syndrome (primary immunologic deficit), Velo-Cardio-Facial-Syndrome (VCFS; velopharyngeal, heart, and facial anomalies), and Conotruncal Anomaly Face Syndrome (primary heart defect with facial dysmorphologies). Whereas the physical phenotype is heterogeneous, the neurocognitive profile is far more consistent. Researchers have estimated that 90% to 100% of 22q11 DS children are learning disabled (e.g., Lipson et al., 1991;Shprintzen, Goldberg, Young, & Walford, 1981) and hypotonic, with gross and fine motor dyscoordination, associated expressive language delays, attention impairment, and behavioral anomalies . Frank mental retardation is relatively rare and may be associated with prolonged anoxia during early cardiac failure. Of urgent concern, approximately 25% of 22q11 DS children are estimated to develop early adulthood schizophrenia (Murphy & Owen, 1996; Pulver et al., Copyright © 2004 The neurocognitive performance of 22q11 DS children is notably complex however and visuospatial memory deficits alone are unlikely to fully explain their profiles. In fact when a broader complement of abilities was examined additional areas of deficit were revea...

The 22q11 Deletion Syndrome (22q11DS) is among the most frequent gene deletion disorders, occurring once in every 6,000 live births. Descriptive reports have suggested marked social differences in affected children. Empirical studies are needed to verify possible social skills deficits among children with 22q11DS, and also to examine possible associations between their frequently reported executive function deficits and social anomalies.Fifty-two parents of affected children (n = 52) and participating control siblings (n = 26) completed the Social Skills Rating System (SSRS) and Behavior Inventory of Executive Function (BRIEF).When compared with control siblings, children with 22q11DS had significantly lower SSRS ratings for Cooperation, Assertion, Responsibility, and Self-Control. Affected children had significantly higher BRIEF ratings for Initiation, Planning, Working Memory, and Monitoring. In affected children, global Social Skill was negatively correlated with BRIEF Global Composite scores. Initiation and Monitoring significantly predicted Social Skill. Children with 22q11DS have marked differences in social skill development which are associated with executive dysfunction. Keywords22q11 Deletion Syndrome; executive function; social skill; remediation; children; neuropsychology The 22q11 Deletion Syndrome (22q11DS) is one of the most common known genetic disorders, estimated to occur in one of every 6,000 live births (Botto et al., 2003). The syndrome results in the loss of a 1.5 megabase region on the long arm of chromosome 22 at the 11.2 site. In the vast majority of cases, the deletion is not transmitted by either parent (de novo). Children with 22q11DS have an array of anomalies believed to be associated with the loss of genes in this region, including physical, neurocognitive, behavioral, and social differences. With regard to their physical phenotype, over 180 possible anomalies have been described (Ryan et al., 1997), the most common of which include structural differences of the head, ears, throat, and neck, possibly accompanied by early feeding difficulties (reflux), immunologic problems, heart defects of widely varying severity, and early hypotonia. Prior to the identification of a single underlying deletion, children with this syndrome were identified according to their primary physical problem, including DiGeorge Syndrome (primary immunological deficit), Conotruncal Anomaly Face Syndrome (primary heart defect with facial dysmorphologies), and Velo-Cardio-Facial Syndrome (primary dysmorphologies of the face and head with varying cardiac irregularities). Any given child, however, may have several or none of these physical problems (although most children have been noted to have at least minor structural facial differences). In this way, the physical phenotype associated with 22q11DS is quite broad, and may determine whether and how early a child's deletion is detected.Although their physical phenotype varies greatly, the neurocognitive development of children with 22q11DS is proving to be...

The 22q11 deletion syndrome (DS) results in the loss of approximately 30 gene copies and is associated with possible physical anomalies, varied learning disabilities, and a specific cluster of neurocognitive deficits, including primary impairment in working memory, executive visual attention, and sensorimotor processing. Retrospective studies have suggested that children with 22q11DS are at 25 times greater risk of developing schizophrenia, thus specification of early brain network vulnerabilities among children with 22q11DS is critical. Previously, we reported that children with 22q11DS as compared with sibling controls had selective deficits in visual executive attention, and subsequently found lowered prepulse inhibition (PPI) in these same children. Visual executive attention and PPI recruit the same brain pathways linking prefrontal cortex to basal ganglia structures. To test the specificity of brain pathway vulnerability among children with 22q11DS, we examined visual executive attention and PPI paradigm data collected during the same test session from 21 children with 22q11DS and 25 sibling controls. We predicted lower %PPI and less efficient executive attention scores, and a significant inverse correlation between measures. %PPI in children with 22q11DS as compared with sibling controls was 20% lower, and visual executive attention efficiency scores 40% worse. As predicted, %PPI was inversely correlated only with executive attention efficiency scores. The implications of these findings with regard to brain pathway vulnerability in children with 22q11DS are considered. These results suggest that children with 22q11DS have early functional abnormality in pathways linking the prefrontal cortex and basal ganglia. Molecular Psychiatry (2005) 10, 553-562.