The cognitive development of children with the 22q11.2 deletion syndrome

Abstract

Background: The 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with palatal abnormalities, cardiac defects and characteristic facial features. On a behavioural/ psychiatric level, children with 22q11DS are at an increased risk for various psychiatric problems, including Autism Spectrum Disorders (ASD), Attention Deficit/ Hyperactivity Disorder (ADHD), various anxiety disorders and psychotic disorders. Up to 30% of patients develop schizophrenia during adolescence and early adulthood. Cognitively, 22q11DS is characterized by learning difficulties and delays in speech/ language development. At the start of this thesis in 2000, literature on the systematic examination of the cognitive development of children with 22q11DS was still scarce and reports were largely based on cross-sectional data with small patient groups and wide age ranges. Objective: To systematically study the cognitive and behavioural development of children with 22q11DS in the period between early childhood and adolescence. In particular, the focus was on stability of IQ in time, the relationship between intelligence level and behaviour and the influence of potential confounders such as gender, heart conditions, de novo vs. familiar deletion and level of parental education on IQ. Method: A prospective, longitudinal study design was used, as the interest was on the individual cognitive and behavioural development of children with 22q11DS. Children with 22q11DS (N = 281) underwent cognitive and behavioural assessments at set ages (1½, 3½, 5½, 7½, 9½ and 15½ years of age) at the Wilhelmina Children’s Hospital, University Medical Centre Utrecht, between 2000 and 2011. Where possible, raw score development was analysed. Results: Children with 22q11DS have a distinctive cognitive development. Most importantly, the findings of this thesis indicate that in 22q11DS, cognitive level is unstable and actually declines with age. In some children this is the result of not being able to keep up with their peers (‘growing into deficit’).However, in about a third of the children a complete stagnation or even a decline in raw test scores was found; there was a measurable loss of cognitive abilities in the transition from childhood to adolescence in 22q11DS. Also, where in the general population a low intelligence level is a predictor of behavioural problems, this is not the case in 22q11DS. No relationship was found between FSIQ and familiar/ de novo deletion, level of parental education or the presence of a heart condition. Gender on the other hand was a main confounder and predictor of intelligence level, girls performed better than boys but also declined more severely. Conclusions: Children with 22q11DS follow a unique developmental trajectory suggestive of a 22q11DS cognitive phenotype. A novel finding of our study is that the cognitive transition from childhood to adolescence in 22q11DS is characterized by an absolute cognitive decline in a substantial amount of these children. Cognitive deterioration is severe in some but does not appear to predict behavioural problems in early adolescence. Whether a decline in intelligence predicts psychosis in 22q11DS remains to be investigated.