A distinct cognitive profile in individuals with 3q29 deletion syndrome

Abstract Background 3q29 deletion syndrome is associated with mild to moderate intellectual disability. However, a detailed understanding of the deletion’s impact on cognitive ability is lacking. The goal of this study was to address this knowledge gap. A second goal was to ask whether the cognitive impact of the deletion predicted psychopathology in other domains. Methods We systematically evaluated cognitive ability, adaptive behavior, and psychopathology in 32 individuals with the canonical 3q29 deletion using gold-standard instruments and a standardized phenotyping protocol. Results Mean FSIQ was 73 (range 40-99). Verbal subtest score (mean 80, range 31-106) was slightly higher and had a greater range than nonverbal subtest score (mean 75, range 53-98). Spatial ability was evaluated in a subset (n = 24) and was lower than verbal and nonverbal ability (mean 71, range 34-108). There was an average 14-point difference between verbal and nonverbal subset scores; 60% of the time the verbal subset score was higher than the nonverbal subset score. Study subjects with a verbal ability subtest score lower than the nonverbal subtest score were 4 times more likely to have a diagnosis of intellectual disability (suggestive, p-value 0.07). The age at which a child first spoke two-word phrases was strongly associated with measures of verbal ability (p-value 2.56e-07). Cognitive ability was correlated with adaptive behavior measures (correlation 0.42, p-value 0.02). However, though group means found equivalent score, there was, on average, a 10-point gap between these skills (range −33 to 33), in either direction, in about 50% of the sample suggesting that suggesting that cognitive measures only partially inform adaptive ability. Cognitive ability scores did not have any significant relationship to cumulative burden of psychopathology nor to individual neurodevelopmental or psychiatric diagnoses. Conclusions Individuals with 3q29 deletion syndrome have a complex pattern of cognitive disability. Two-thirds of individuals with the deletion will exhibit significant strength in verbal ability; this may mask deficits in non-verbal reasoning, leading to an over-estimation of overall ability. Deficits in verbal ability may be the driver of intellectual disability diagnosis. Cognitive ability is not a strong indicator of other neurodevelopmental or psychiatric impairment; thus individuals with 3q29 deletion syndrome who exhibit IQ scores within the normal range should receive all recommended behavioral evaluations.