Chromosome 22q11.2 deletion syndrome (DS22q11.2) is a congenital condition known to affect brain development and cognition that occurs in 1–2 out of every 4,000 live births . The syndrome results from a microdeletion on the long arm (q) of the 22nd chromosome and has been identified as the molecular cause for several symptom-based medical diagnoses . Medical characteristics associated with the syndrome typically include palatal abnormalities and/or velopharyngeal insufficiency, immune deficiency, congenital cardiac defects, neonatal hypocalcemia, and facial dysmorphisms [3, 4]. Individuals with DS22q11.2 are also at an increased risk for developing psychiatric disorders such as ADHD , obsessive-compulsive disorder , affective disorders , autism , and schizophrenia . Significant intellectual impairments are often observed as well . However, at present, far less is known about the cognitive characteristics than for the medical indications.
Impairment in general intellectual functioning is one of the most consistently reported features in DS22q11.2 . IQ scores typically fall in the range of 70–85, one full standard deviation or more below the population mean. Empirical investigations have demonstrated that low performance on IQ assessments are not the result of the physical or medical characteristics [10, 11], nor the associated behavioral problems that commonly accompany the syndrome . Studies of academic achievement have attempted to further clarify these cognitive difficulties and report that children with DS22q11.2 perform better at reading and spelling than arithmetic . This specific pattern of cognitive strengths and weaknesses has lead to the hypothesis that the cognitive difficulties are the cascaded effects of core deficits in visuospatial processing and attention, both of which are primarily mediated by cortical networks in the parietal and temporal lobes [14–16].
At least some of the genetic material in the deleted segment (30–40 genes) appears to be related to typical brain development, as anomalous brain structure is consistently reported [17, 18]. Thus far, characterization of the expression of DS22q11.2 in terms of neurodevelopment has come from studies using structural and function magnetic resonance imaging and diffusor tensor imaging in children, adolescents, and adults with the syndrome [18–21]. The most reliable neuroanatomical finding thus far is an overall reduction in total brain volume ranging from 8.5–11% that appears more concentrated in the posterior and inferior regions of the brain [19–21]. During childhood, volumetric reductions in the temporal lobe have been reported as the result of decreases in both gray and white matter . Similarly, studies in adulthood also report reductions in temporal lobe volume, with greatest reductions emerging in the presence of marked psychopathology [18, 23].
Although the number of studies examining individual structures (i.e., amygdala and hippocampus) in the temporal lobes is increasing, findings to date have been variable (cf. [22, 24–26]). Some of this heterogeneity can be attributed to small sample sizes, differences in the ages, cognitive abilities, and psychiatric symptoms of those tested, the control groups chosen for comparison, the methods used to determine anatomical boundaries, and the covariates used in analyses. For example, disproportionate decreases in hippocampal volume have not typically been reported when total brain volume is used as a covariate (e.g., [22, 26]), but have been reported when total gray matter is used (e.g., [24, 25]). Moreover, these findings are difficult to compare directly given the wide range of ages and cognitive abilities of the participants, as well as variations in the tracing methods used for volumetric analyses (cf.; [27, 28]).
Thus, although some progress has been made in characterizing the neuroanatomical differences within this population, the implications for neurocognitive outcomes remain poorly understood. Bearden and colleagues  have begun to address this issue by relating regional brain abnormalities with cognitive ability and behavioral phenotype in a sample of 13 children with DS22q11.2. Results of this investigation indicated that only temporal lobe volume (both gray and white matter) significantly predicted overall cognitive performance in children with DS22q11.2 . Specifically, temporal lobe volume was a significant positive predictor of Full Scale and Verbal IQ, but not Performance IQ (as measured by WISC-III). In addition, Bearden et al.  report a negative correlation between Thought Problems as assessed by the Child Behavior Checklist (CBCL; ) and temporal lobe gray matter volume.
Within the temporal lobe are two structures on which much empirical research has been conducted: the amygdala (implicated in emotion and social behavior) and the hippocampus (well-known for its role in memory and spatial cognition). Investigation of these individual structures may provide more detail regarding regionally specific changes within the temporal lobe network. While the hippocampus has been measured volumetrically in DS22q11.2 and has been hypothesized to be related to risk for psychopathology  and memory impairments , to our knowledge, no evidence exists to date regarding the functional significance resulting from these observed abnormalities. Studies with typically developing children have suggested that the hippocampus is correlated with both IQ  and memory (see  for review). Also relevant for studies of children with DS22q11.2, there is evidence of associations between reductions in hippocampus volume in schizophrenia (see  for review), which may make assessment of this structure important for risk assessment and prediction of outcomes.
In short, the purpose of present investigation was to expand on previous research examining neuroanatomical differences in children with DS22q11.2 and link these findings to resulting cognitive outcomes. The ultimate goal of this line of research is to gain further insight into complex gene-brain-behavior relations associated with this syndrome and improve outcome predictions. Volumetric measurements of regions within the temporal lobe, namely the hippocampus and amygdala, were measured bilaterally from structural MRIs in 72 children and adolescents with and without DS22q11.2. Associations with intellectual ability were assessed.