VIP Summary #9: Duplication of 16p11.2: Defining the Effect on Cognition, Behavior, and Medical Comorbidities

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

D’Angelo et al.’s publication reviews which physical traits are associated with a duplication of the 16p11.2 region. The main objective of this study was to compile a list of common features shown in behavior, cognitive performance, and physical traits and to determine the degree to which these features are present in people with the16p11.2 duplication. In other words, when we look at a large group of people with a 16p11.2 duplication, which traits or features tend to be most common? How mild or severe are these traits and what influences their severity?

The study identified 1006 participants from Europe and the United States. 270 of the study participants had the 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 to members of their families, including siblings of a similar age and biological parents (102 “control” subjects from duplication families). Data from these 16p11.2 duplication families were also compared with previously reported data from 16p11.2 deletion families (390 individuals with the deletion/244 control subjects from deletion families). Many of these participants were enrolled through Simons VIP!

To create a broad picture of how 16p11.2 duplications and deletions affect an individual, researchers compared measures of:

  1. IQ for cognitive performance
  2. Neurologic and psychological symptoms, such as the frequency of additional disorders like epilepsy and the diagnosis of autism spectrum disorders (ASD)
  3. Body mass index (BMI) and head circumference (HC) to track physical features

Having an understanding of what common features to expect in a genetic disorder makes it easier for families to plan for the future. Learning from families now, helps other families today and in the future, to benefit from the knowledge gained. It also helps healthcare providers to develop appropriate follow-up plans for children with the 16p11.2 duplication.

Thinking and Learning: Study participants were scored on three categories, full scale IQ, verbal IQ and non-verbal IQ, to accommodate different learning styles and show strengths and weaknesses. Individuals may be good in one type of learning, but do poorly in another, and a range of testing criteria helps pinpoint what areas to focus on in providing supportive education. This study assessed the overall effect of the 16p11.2 duplication on IQ and found that individuals with the 16p11.2 duplication had an average full scale IQ (FSIQ) of 78.8. However, there was increased variability in IQ for subjects with the duplication; some individuals had lower than average IQs, while others had higher than average IQs. This variability may be due to how subjects were identified. Children with the duplication may have originally been identified due to cognitive impairment (lower IQ). Parents and siblings who are found to have the duplication after their family member was identified may have less cognitive impairment (higher IQ).

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

  • The dotted line illustrates the IQ distribution of individuals who have the duplication and ASD. The majority of these individuals have an IQ near 40.
  • The solid line illustrates the IQ distribution of individuals who have the duplication, but have not been diagnosed with ASD. The majority of these individuals have an IQ near 80, which is closer to the average IQ of 100 in healthy, control individuals.

Neurologic/Psychological Symptoms:The comparisons of average IQs of study participants suggest that the 16p11.2 duplication is associated with a low-functioning form of ASD. The frequency of ASD in individuals that have a 16p copy number variant is similar, with 16% of deletions carriers and 20% of duplication carriers having been diagnosed. Epilepsy was seen in 21.8% of people who have duplication and 19.4% of people who have the deletion. Both ASD and epilepsy diagnoses were equally frequent among the deletion and duplication carriers, but these are only associated with the individuals with lower IQ scores in the duplication group.

Physical Characteristics: This study found that participants with the 16p11.2 duplication were more commonly underweight, whereas obesity was more frequent among people with the deletion. This was in comparison to the BMIs of family members that did not carry either the duplication or the deletion. Additionally, head circumference (which is correlated with brain volume) was decreased in those with the duplication (22.3% of duplication subjects) and was associated with non-verbal IQ. This decrease in head circumference occurs during the first two years of life. Major medical malformations were seen in 16.7% of duplication individuals and 21.1% of deletion individuals. The most common were scoliosis, genital and cardiac malformations in both duplication and deletion individuals.

Future studies will aim to determine how these additional factors contribute to the observed cognitive, behavioral, and physical traits of individuals with the16p11.2 duplication; the research here serves as a great starting point.

We appreciate our families’ contributions to Simons VIP Connect; through your research participation we can continue to gain a better understanding of these genetic changes and their overall effect on people and their families.

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