An investigation of the neuropsychological profile in adults with velo-cardio-facial syndrome (VCFS)

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Abstract

Velo-cardio-facial syndrome (VCFS) is associated with deletions on the long arm of chromosome 22, mild intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies investigating the neuropsychological functioning of adults with VCFS. We compared 19 adults with VCFS with 19 age, gender and IQ matched controls using a comprehensive neuropsychological battery. Compared to controls, adults with VCFS had significant impairments in visuoperceptual ability (Visual Object and Space Perception Battery), problem solving and planning (Tower of London) and abstract and social thinking (Comprehension WAIS-R). It is likely that haploinsufficiency (reduced gene dosage) of a neurodevelopmental gene or genes mapping to chromosome 22q11 underlies the cognitive deficits observed in individuals with VCFS.

Introduction

Velo-cardio-facial syndrome (VCFS), a relatively common genetic syndrome (occurring in ≈1:4000 live births) is associated with deletions on the long arm of chromosome 22 [7], [32], [26]. The clinical phenotype is variable but cleft palate, cardiac anomalies, a typical facial appearance and intellectual disabilities are the most common [30], [11]. Behavioural characteristics include social withdrawal, shyness and impulsivity with poor attention and concentration [9]. Furthermore, children with VCFS score higher on measures of anxiety and depression than children in the general population [32]. Recently attention has also focused on VCFS because it is associated with a high prevalence of neuropsychiatric disorders, including schizophrenia in adolescence and adulthood [23], [24], [31].

Intellectual disability has been reported as one of the major features of VCFS. Thus far, research has focused largely on children with VCFS and the majority are reported to have mild intellectual disabilities (ranging from moderate through to average ability) [9], [32]. To date, the most consistent finding from the child and adolescent literature is the discrepancy between Verbal and Performance IQ on tests of general intellectual functioning. Several studies have reported differences between Verbal and Performance IQ, indicating superior verbal skills [8], [32]. It has been postulated that this discrepancy is related to a combination of impairments in visuospatial ability, planning ability, non-verbal reasoning and deficits in novel reasoning and concept formation [8]. However, these conclusions have been made based on the administration of tests of general intellectual functioning in children without comparison to an IQ matched control group. Furthermore, it remains unclear whether these findings are specific to children (i.e. are these deficits also present in adults?) or VCFS (i.e. are these deficits associated with lower levels of intellectual ability?). Moreover, other cognitive domains such as memory and executive functioning have not yet been studied in VCFS due to the focus on developmental and attainment issues.

Until recently little was known about the neurobiology underlying neuropsychological deficits and psychiatric disorders associated with VCFS. Most structural neuroimaging studies have been qualitative, whilst the few quantitative studies performed have been carried out with children. The majority of these studies suffer methodological flaws including small sample sizes and an absence of appropriately matched control groups. Nevertheless, consistently reported findings have included the presence of a small cerebellum, white matter hyperintensities and developmental midline abnormalities [6], [15]. Recently however, in a quantitative neuroimaging study of VCFS adults, van Amelsvoort et al. [40] reported that, compared to an age and IQ-matched control group, adults with VCFS exhibited widespread differences in white matter bilaterally and regional specific differences in left cerebellum, insula, frontal and right temporal lobes.

The neuropsychological profile of adults with VCFS has not been previously reported. Consequently, we undertook the current study using a comprehensive neuropsychological test battery covering major areas of functioning including intelligence, memory, attention and executive functioning to compare a group of VCFS adults to a matched IQ, age and gender control group.

Section snippets

Subjects

VCFS participants were recruited from the University of Wales College of Medicine, Cardiff and the Behavioural Genetics Clinic, Institute of Psychiatry, London and were ascertained from a variety of sources. Some 16 (84%) were recruited from numerous departments of medical genetics throughout England and Wales, two (11%) were recruited from psychiatric services and one (5%) was recruited from the cardiology services. Participants underwent genetic, physical and psychiatric examinations and

Results

The VCFS group had a mean Full Scale IQ (FSIQ) of 74 (S.D. 11.46). Distribution of IQ scores showed: 42% in the mildly intellectually disabled range (FSIQ 58–67), 37% in the borderline range (FSIQ 71–82) and 21% in the average range of intellectual functioning (87–97). Six (32%) VCFS participants were found to have a significant discrepancy (11 points or more) [37] in favour of performance ability, three (16%) had a significant discrepancy in favour of Verbal ability and over half of the group (

Discussion

In this study, our aim was to examine the neuropsychological profile in adults with velo-cardio-facial syndrome and to investigate whether there are specific cognitive deficits associated with this group. We found that the VCFS group performed significantly worse than controls on the Comprehension subtest of the WAIS-R, Silhouettes and Object Decision subtests of the VOSP and accuracy of problem solving on the ToL. In addition, the VCFS group used significantly less planning time on the ToL

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