Motor difficulties in 16p11.2 copy number variation

The rare genetic variants 16p11.2 duplication and 16p11.2 deletion have opposing effects on brain structure and function, yet are associated with broadly similar clinical phenotypes that include autism, intellectual impairment, psychiatric illness, and motor difficulties. In recent years, studies have identified subtle distinctions between the phenotypic effects of 16p11.2 duplication and 16p11.2 deletion with respect to patterns of autism, intellectual impairment, and psychiatric illness. However, although divergent phenotypic findings in some motor domains have been reported, no study has yet made a comprehensive comparison of motor difficulties between 16p11.2 deletion and 16p11.2 duplication carriers to elucidate points of convergence and divergence. We sought to make such a comparison in a group of 133 16p11.2 deletion carriers, 122 duplication carriers, and 388 familial controls, hypothesizing that motor impairment would overall be greater in deletion than duplication carriers. In a series of regression models, we found that 16p11.2 deletion status tended to predict greater impairment along indices of gross motor function, but less impairment along indices of fine motor function. These findings point to a potential pattern of performance difficulties that could be investigated in future studies. Elucidating motor differences between 16p11.2 duplication and 16p11.2 deletion carriers may help in understanding the complex effect of 16p11.2 copy number variation and other rare genetic causes of autism. 16p11.2 deletion and 16p11.2 duplication are reciprocal genetic changes in which a small segment of chromosome 16 is missing (deletion) or has an extra copy present (duplication). The deletion and duplication can both cause autism, but since each has a different effect on brain structure and function, we wanted to investigate whether they have different effects on motor behavior. We found that 16p11.2 deletion may be more likely to cause problems with motor skills that require whole body movement, and 16p11.2 duplication may be more likely to cause problems with motor skills that require precise movement of the fingers.