Genotype–Phenotype Association Studies of Chromosome 8p Inverted Duplication Deletion Syndrome

Individuals diagnosed with chromosome 8p inverted duplication deletion (invdupdel(8p)) manifest a wide range of clinical features and cognitive impairment. The purpose of this study is to employ array CGH technology to define more precisely the cytogenetic breakpoints and regions of copy number variation found in several individuals with invdupdel(8p), and compare these results with their neuropsychological characteristics. We examined the cognitive-behavioral features of two male and two female children, ages 3–15 years, with invdupdel(8p). We noted cognitive deficits that ranged from mild to severe, and adaptive behavior composites that ranged from significantly to substantially lower than adequate levels. CARS scores, a measure of autistic behavior, identified three children with autism or autistic-like features. Three of the four children exhibited attention deficits and hyperactivity consistent with a DSM-IV-TR diagnosis of ADHD. One child showed extreme emotional lability. Interestingly, intellectual disability was not correlated with deletion size, nor was the deletion location associated with the autistic phenotype. On the other hand, the duplication length in 8p21.1/8p22 was associated with cognitive deficit. In addition, a small locus of over-expression in 8p21.3 was common for all three participants diagnosed as autistic. A limitation of the study is its small sample size. Further analyses of the deleted and over-expressed regions are needed to ascertain the genes involved in cognitive function and, possibly, autism.