Neurocognitive development in 22q11.2 deletion syndrome: comparison with youth having developmental delay and medical comorbidities

Abstract

The 22q11.2 deletion syndrome (22q11DS) presents with medical and neuropsychiatric manifestations including neurocognitive deficits. Quantitative neurobehavioral measures linked to brain circuitry can help elucidate genetic mechanisms contributing to deficits. To establish the neurocognitive profile and neurocognitive “growth charts”, we compared cross-sectionally 137 individuals with 22q11DS ages 8–21 to 439 demographically matched non-deleted individuals with developmental delay (DD) and medical comorbidities and 443 typically developing (TD) participants. We administered a computerized neurocognitive battery that measures performance accuracy and speed in executive, episodic memory, complex cognition, social cognition and sensorimotor domains. The accuracy performance profile of 22q11DS showed greater impairment than DD, who were impaired relative to TD. Deficits in 22q11DS were most pronounced for face memory and social cognition, followed by complex cognition. Performance speed was similar for 22q11DS and DD, but 22q11DS individuals were differentially slower in face memory and emotion identification. The growth chart, comparing neurocognitive age based on performance relative to chronological age, indicated that 22q11DS participants lagged behind both groups from the earliest age assessed. The lag ranged from less than a year to over three years depending on chronological age and neurocognitive domain. The greatest developmental lag across the age range was for social cognition and complex cognition, with the smallest for episodic memory and sensorimotor speed, where lags were similar to DD. The results suggest that 22q11.2 microdeletion confers specific vulnerability that may underlie brain circuitry associated with deficits in several neuropsychiatric disorders and thereby help identify potential targets and developmental epochs optimal for intervention.

Neurodevelopmental outcome in 22q11.2 deletion syndrome and management

“…Thus, learning difficulties are very common in preschool and primary school, especially within the domains of mathematics (De Smedt et al, 2009a, 2009b; Tobia, Brigstocke, Hulme, & Snowling, 2017; Wang, Woodin, Kreps-Falk, & Moss, 2000) and language comprehension (Glaser et al, 2002; Van den Heuvel et al, 2016). Cognitive deficits are seen in the majority (90–100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory, and visual-spatial perception (Antshel, Fremont, & Kates, 2008; Campbell & Swillen, 2005; Gur et al, 2014). In a recent cross-sectional study (Gur et al, 2014), the cognitive functions of 137 subjects (aged 8–21) were compared with youth with a developmental delay and medical comorbidities and with typically developing controls.…”

“…Cognitive deficits are seen in the majority (90–100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory, and visual-spatial perception (Antshel, Fremont, & Kates, 2008; Campbell & Swillen, 2005; Gur et al, 2014). In a recent cross-sectional study (Gur et al, 2014), the cognitive functions of 137 subjects (aged 8–21) were compared with youth with a developmental delay and medical comorbidities and with typically developing controls. Greatest deficits were observed in the domains of complex cognition (verbal language-mediated reasoning, non-verbal reasoning, and spatial processing).…”

Subthreshold Psychotic Symptoms in 22q11.2 Deletion Syndrome

“…5,6 The associated phenotype is variable and can include neuropsychiatric and physical features, with cardiac, palate, endocrine, and immunologic abnormalities. 5,7–9 Psychiatric disorders are common, affecting three quarters of individuals with 22q11DS; there is increased risk for autism, attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, and, most notably, psychosis. 10–15 Approximately a third of individuals with 22q11DS develop psychotic disorders by adulthood, representing a 25-fold increase in psychosis risk over the general population, and 10-fold over other developmentally delayed populations.…”

Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm

“…The 22q11.2DS is also one of the highest known risk factors for the development of schizophrenia; 30%-40% of adults with this syndrome meet diagnostic criteria for a schizophrenia spectrum disorder (Schneider et al, 2014a). In the past decade, a large number of studies have described the cognitive profile of people with 22q11.2DS and have notably shown that executive functioning is a particular weakness (Campbell et al, 2010;Gur et al, 2014;Niklasson & Gillberg, 2010;Shapiro, Wong, & Simon, 2013). For example, Campbell et al (2010) observed that children with 22q11.2DS have impaired planning abilities and limited cognitive flexibility.…”