Theme 3 | Rare diseases

Cognitive and psychiatric phenotype in 22q11.2 deletion and 22q11.2 duplication syndromes: a comparative study.

Chaira Serrarens

Chaira Serrarens1, Claudia Vingerhoets1 & Therese van Amelsvoort1

1 Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, The Netherlands

Microdeletions and microduplications on chromosome 22 are associated with an increased risk of cognitive deficits and psychiatric disorders. Nonetheless both syndromes display considerable variation in the spectrum and severity of its expression between individuals (1-2). In contrast to 22q11.2 deletion syndrome (22q11.2DEL), less studies have investigated the 22q11.2 duplication syndrome (22q11.2DUP) and comparative studies between the syndromes are scarce. These studies are important to delineate copy number variant (CNV) specific deficits. Therefore, in the present study we compared the cognitive and psychiatric profile between 22q11.2DEL and 22q11.2DUP. 

In total, 73 subjects with 22q11.2DEL and 8 subjects with 22q11.2DUP were enrolled in this cross-sectional study. Cognitive functioning was assessed using The Cambridge Neuropsychological Automated Test Battery (CANTAB). Cognitive scores were computed for 7 separate domains: verbal and visual learning and memory, working memory, attention, processing speed, executive functioning and social cognition. Presence of psychiatric disorders was assessed using the Mini-international Neuropsychiatric Interview (M.I.N.I.; 3). Intelligence quotient (IQ) was estimated using a shortened version of the Wechsler Adult Intelligence Scale (WAIS-III; 4). 

Gender (p=0.14), age (p=0.075) and adaptive skills (p=0.33) did not significantly differ between groups. IQ was found to be significantly higher (p<0.01) in 22q11.2DUP individuals showing an average IQ of 88.75 compared to an average IQ of 73.63 in 22q11.2DEL individuals. The groups did not significantly differ in presence of psychiatric disorders. Adults with 22q11.2DUP performed significantly better on a working memory (p=0.02) and executive functioning (p=0.043) task compared to 22q11.2DEL subjects. No group differences were found for other cognitive domains. 

Although the sample size is too small to be conclusive, these preliminary results could indicate a comparable psychiatric profile between the 22q11.2DUP and 22q11.2DEL syndrome. In addition, these results could indicate better cognition in 22q11.2DUP individuals compared to 22q11.2DEL individuals. Better cognitive functioning and supposedly better physical health in the 22q11.2DUP group perhaps results in underdiagnosis of this CNV. However, physical features are not taken into account in this study. Our results point out the need for more comparative studies with a larger 22q11.2DUP sample, perhaps identifying CNV specific differences in psychiatric profiles as well.

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