Defining the effect of 16p11.2 duplication on cognition, behavior, and medical comorbidities

Original research article by Debra D’Angelo et al. (2015).

Read the abstract here.

In this article, the researchers explored which traits or features are most common among people with a 16p11.2 duplication. They also studied how mild or severe these traits can be and what influences their severity.

Taking part in the study were 1,006 people in Europe and the United States. Among the study participants, 270 had a 16p11.2 duplication. To help understand the role of family background in how features of the duplication are expressed, the duplication-carrying participants were compared with members of their families, including siblings of a similar age and their biological parents. This group consisted of 102 people from duplication families. Data from these families were also compared with previously reported data from 16p11.2 deletion families (390 people with the deletion and 244 control subjects from deletion families). Many of these participants were enrolled through Simons Searchlight.

To examine how 16p11.2 duplications and deletions affect a person, researchers compared:

  • IQ
  • Neurological and psychological symptoms, such as the frequency of additional disorders like epilepsy and autism spectrum disorder
  • Body mass index and head circumference

Thinking and Learning: Study participants were scored on three categories–full scale IQ, verbal IQ, and nonverbal IQ–to accommodate different learning styles and identify strengths and weaknesses. People with the 16p11.2 duplication had an average full scale IQ of 78.8. The full scale IQs of individuals with the 16p11.2 duplication and the 16p11.2 deletion were similar, but the IQs of those with the duplication showed more variability. This might indicate that additional genetic factors may have a significant role in cognition in those with the duplication, and less of a role in those with the deletion.

This graph shows the range of full scale IQs for study participants who have the 16p11.2 duplication. 

  • The dotted line illustrates the FSIQ distribution of people who had the duplication and ASD. The average IQ of this group was about 40.
  • The solid line illustrates the IQ distribution of people who have the duplication but had not been diagnosed with ASD. The average IQ of this group was about 80, closer to the IQ of control groups.

Neurological and Psychological Symptoms: IQ scores for individuals with 16p11.2 duplication and autism were significantly lower than the IQ scores of those with only the duplication. About the same percentage of 16p11.2 duplication and deletion carrying individuals had an autism diagnosis: 20 and 16, respectively. Similar percentages were seen with epilepsy diagnoses, with 21.8% of duplication carriers and 19.4% of deletion carriers.

Physical Characteristics: Individuals with the 16p11.2 deletion were much more likely to be overweight in contrast to those with the 16p11.2 duplication who were more likely to be underweight when compared to the BMI scores of family members without the gene changes.  Additionally, head circumference (which is correlated with brain volume) was decreased in those with the duplication (22.3% of duplication subjects) and was positively associated with nonverbal IQ. This relative decrease in head circumference begins during the first two years of life. Major medical malformations were seen in 16.7% of the duplication group and 21.1% of the deletion group. The most common malformations were scoliosis and genital and cardiac malformations, appearing in both duplication and deletion groups.