Cognitive development in VCFS

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Abstract

The 22q11.2 microdeletion (velocardiofacial syndrome, VCFS) results in a complex pattern of psychoeducational and neurocognitive deficits. Mean full-scale IQ scores are in the range of borderline intellectual function, but academic achievement scores are generally in the low–normal range. A dichotomy is often found between higher Verbal IQ scores and lower Performance IQ, paralleled by relative strength in Reading and Spelling, but weakness in Math. Language skills are also typically delayed and remain impaired later in life, and psychiatric disorders can be found in both children and adults with the syndrome. On-going neurocognitive research suggests that the impairment in mathematical ability may be associated with poor visual–spatial skills. This would be consistent with theoretical models that link arithmetic skills with visual attention and spatially referenced representations of magnitude. Neuroimaging investigations indicate that these skills may all depend critically on the inferior parietal lobes, and lead to our hypothesis that these may be dysfunctional in the 22q11.2 syndrome. Early reports find no association between cognitive ability in the syndrome and the presence of cardiac malformations.

Introduction

The purpose of this review is to address issues relating to the cognitive development of children with velocardiofacial syndrome (VCFS). Compared with work focusing on the medical implications of the syndrome, this is an area of relative novelty. Many questions have yet to be asked concerning the intellectual outcomes of affected children. These questions can be addressed at different levels and each requires its own set of methodologies. In this review, we focus on two levels of analysis where some progress has been made. The first is the area of standardized testing of intelligence, academic achievement and neuropsychological function. At present, this represents the largest body of knowledge regarding intellectual function in children with VCFS. Despite considerable variation in the phenotype, there is general consensus in the picture that has emerged. The second area, just getting underway, focuses on functional neurocognitive analysis. Taking the neuropsychological testing data as its starting point, these studies are now examining specific cognitive processes and the neural substrates involved in their implementation in order to provide mechanistic and integrative explanations as to why certain clusters of cognitive dysfunction are observed. This work also will also lay the groundwork for subsequent cognitive interventions that may be able to reduce, or even remove, some deficits by ‘retraining’ the brains of children with VCFS early in development to process certain kinds of information in ways that are more suited to their areas of strength. Although some brain and cognition findings have been published about adults with VCFS, we focus this review on children.

Section snippets

Psycho-educational and neuropsychological findings

What is known so far about the cognitive implications of VCFS? The broad psychoeducational picture is, in fact, fairly clear. Children with VCFS show mean full-scale IQ scores (FSIQ) in the range of borderline intellectual abilities, with verbal IQ (VIQ) significantly higher than performance IQ scores (PIQ) [1], [2], [3] (Fig. 1). In the largest study to date, Moss et al. [1] reported a FSIQ of 71.2±12.8 (mean±standard deviation), VIQ 77.5±14.9, and PIQ 69.1±12.0, in a group of 33 subjects.

Cognitive process findings

Therefore, everything we have reviewed so far, from IQ subscores to specific neuropsychological function tests, suggests that a common pathway between visuospatial and numerical deficits in VCFS may lie in the dysfunction of brain areas primarily responsible for representing spatial information and for supporting the cognitive functions common to visuospatial and numerical competence. A good deal of evidence points to the inferior parietal lobes (IPL) as that substrate. Clinical findings and

Cognitive development and cardiac status

An important question regarding the findings discussed above, particularly for this review, concerns the role of cardiac anomalies in these deficits. While the actual prevalence of cardiac defects associated with the deletion is not definitively known, such a diagnosis was made in 74% of the 250 patients observed by the Children's Hospital of Philadelphia clinic [23]. The most common anomalies reported in an earlier survey of this sample were tetralogy of Fallot (TOF), interrupted aortic arch

Psychiatric concerns

A wide range of behavioral and psychiatric concerns has been reported in children with the 22q microdeletion. These include concerns related to hyperactivity and inattention, and anxieties and social withdrawal [4], [6]. Studies utilizing parent report data (i.e. Child Behavior Checklist) indicate significantly elevated rates of attention and internalizing problems in children with VCFS [4], [51], [52]. It is not clear whether the attentional concerns are specific to the syndrome or whether

Summary

Clearly, most children with VCFS have some serious cognitive deficits that have negative implications for outcomes. Little or no formal investigation appears to have taken place concerning what might be called ‘situational’ implications of the syndrome for cognitive development. However, children with VCFS face a range of medical challenges and procedures early in life, and the effect of these on opportunities for early learning and the implications for brain development will be important to

Future approaches

Clearly the time and conditions are now right for extensive studies of brain and cognitive implications of VCFS. Links to specific cognitive processes underlying a range of deficits in VCFS are now being made. In addition, new neuroimaging techniques allow researchers to examine how and why differences in brain structure and function may alter the way these processes work in individuals with VCFS. Many questions remain about the precise role of cardiac defects in those neurocognitive processes,

Acknowledgements

We thank the children, adults and families who have participated in our studies of VCFS. Dr Michael F. Woodin, Mr David O. Aleman and others have greatly contributed to these studies. Much of the research described and the writing of this manuscript were supported in part by grants from the National Institutes of Health, DC 02027 and HD 01174.

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