. 2015 May 1;77(9):785-93.

doi: 10.1016/j.biopsych.2014.04.021. Epub 2014 Jun 16.

The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population

Ellen Hanson¹, Raphael Bernier², Ken Porche³, Frank I Jackson³, Robin P Goin-Kochel⁴, LeeAnne Green Snyder³, Anne V Snow⁵, Arianne Stevens Wallace², Katherine L Campe³, Yuan Zhang⁶, Qixuan Chen⁶, Debra D'Angelo⁶, Andres Moreno-De-Luca⁷, Patrick T Orr⁸, K B Boomer⁹, David W Evans⁸, Stephen Kanne¹⁰, Leandra Berry⁴, Fiona K Miller³, Jennifer Olson³, Elliot Sherr¹¹, Christa L Martin¹², David H Ledbetter¹², John E Spiro¹³, Wendy K Chung¹⁴; Simons Variation in Individuals Project Consortium

Collaborators, Affiliations

Collaborators

Simons Variation in Individuals Project Consortium:
B Aaronson, S Ackerman, H Alupay, K Ankenmann, C Atwell, E Aylward, A Beaudet, M Benedetti, J Berman, R Bernier, A Bibb, L Blaskey, C Brewton, R Buckner, P Bukshpun, J Burko, B Cerban, Q Chen, M Cheong, Z Chu, W Chung, C Dale, A Dempsey, J Elgin, Y Evans, W A Faucett, G Fischbach, S Garza, J Gerdts, S Gobuty, R Goin-Kochel, P E Grant, L Green Snyder, M Greenup, E Hanson, K Hines, L Hinkley, J Hunter, R Jeremy, K Johnson, S Kanne, S Kessler, S Khan, A Laakman, M Lasala, D Ledbetter, H Lee, C Lese Martin, A Lian Cavanagh, A Llorens, T Luks, E Marco, A Martin, G Marzano, K McGovern, R McNally Keehn, D Miller, F Miller, T Moss, P Mukherjee, S Nagarajan, K Nowell, J Olson, J Owen, A Paal, A Packer, P Page, B Paul, N Pojman, M Proud, S Qasmieh, M Ramocki, B Reilly, T Roberts, D Shaw, E Sherr, T Sinha, B Smith-Packard, A Snow, S Spence, J Spiro, K Steinman, A Stevens, V Swarnakar, J Tjernagel, C Triantafallou, R Vaughan, N Visyak, M Wakahiro, T Ward, J Wenegrat

Affiliations

¹ Division of Developmental Medicine, Boston Children's Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: ellen.hanson@childrens.harvard.edu.
² Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
³ Division of Developmental Medicine, Boston Children's Hospital, Boston.
⁴ Department of Pediatrics, Baylor College of Medicine, Houston, Texas;
⁵ Division of Developmental Medicine, Boston Children's Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
⁶ Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
⁷ Autism and Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania; Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania; Department of Radiology, Geisinger Health System, Danville, Pennsylvania;
⁸ Autism and Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania.
⁹ Department of Mathematics, Bucknell University, Lewisburg, Pennsylvania;
¹⁰ Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, Columbia, Missouri.
¹¹ Department of Neurology, University of California, San Francisco, San Francisco, California.
¹² Autism and Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania; Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania.
¹³ Simons Foundation, New York, New York.
¹⁴ Departments of Pediatrics and Medicine, Columbia University, New York, New York.

PMID: 25064419
PMCID: PMC5410712
DOI: 10.1016/j.biopsych.2014.04.021

The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population

Ellen Hanson et al. Biol Psychiatry. 2015.

. 2015 May 1;77(9):785-93.

doi: 10.1016/j.biopsych.2014.04.021. Epub 2014 Jun 16.

Authors

Collaborators

Simons Variation in Individuals Project Consortium:
B Aaronson, S Ackerman, H Alupay, K Ankenmann, C Atwell, E Aylward, A Beaudet, M Benedetti, J Berman, R Bernier, A Bibb, L Blaskey, C Brewton, R Buckner, P Bukshpun, J Burko, B Cerban, Q Chen, M Cheong, Z Chu, W Chung, C Dale, A Dempsey, J Elgin, Y Evans, W A Faucett, G Fischbach, S Garza, J Gerdts, S Gobuty, R Goin-Kochel, P E Grant, L Green Snyder, M Greenup, E Hanson, K Hines, L Hinkley, J Hunter, R Jeremy, K Johnson, S Kanne, S Kessler, S Khan, A Laakman, M Lasala, D Ledbetter, H Lee, C Lese Martin, A Lian Cavanagh, A Llorens, T Luks, E Marco, A Martin, G Marzano, K McGovern, R McNally Keehn, D Miller, F Miller, T Moss, P Mukherjee, S Nagarajan, K Nowell, J Olson, J Owen, A Paal, A Packer, P Page, B Paul, N Pojman, M Proud, S Qasmieh, M Ramocki, B Reilly, T Roberts, D Shaw, E Sherr, T Sinha, B Smith-Packard, A Snow, S Spence, J Spiro, K Steinman, A Stevens, V Swarnakar, J Tjernagel, C Triantafallou, R Vaughan, N Visyak, M Wakahiro, T Ward, J Wenegrat

Affiliations

¹ Division of Developmental Medicine, Boston Children's Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: ellen.hanson@childrens.harvard.edu.
² Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
³ Division of Developmental Medicine, Boston Children's Hospital, Boston.
⁴ Department of Pediatrics, Baylor College of Medicine, Houston, Texas;
⁵ Division of Developmental Medicine, Boston Children's Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.
⁶ Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
⁷ Autism and Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania; Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania; Department of Radiology, Geisinger Health System, Danville, Pennsylvania;
⁸ Autism and Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania.
⁹ Department of Mathematics, Bucknell University, Lewisburg, Pennsylvania;
¹⁰ Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, Columbia, Missouri.
¹¹ Department of Neurology, University of California, San Francisco, San Francisco, California.
¹² Autism and Developmental Medicine Institute, Geisinger Health System, Danville, Pennsylvania; Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania.
¹³ Simons Foundation, New York, New York.
¹⁴ Departments of Pediatrics and Medicine, Columbia University, New York, New York.

PMID: 25064419
PMCID: PMC5410712
DOI: 10.1016/j.biopsych.2014.04.021

Abstract

Background: Deletion of the recurrent ~600 kb BP4-BP5 chromosomal region 16p11.2 has been associated with a wide range of neurodevelopmental outcomes.

Methods: To clarify the phenotype of 16p11.2 deletion, we examined the psychiatric and developmental presentation of predominantly clinically referred individuals, with a particular emphasis on broader autism phenotype characteristics in individuals with recurrent ~600 kb chromosome 16p11.2 deletions. Using an extensive standardized assessment battery across three clinical sites, 85 individuals with the 16p11.2 deletion and 153 familial control subjects were evaluated for symptom presentation and clinical diagnosis.

Results: Individuals with the 16p11.2 deletion presented with a high frequency of psychiatric and developmental disorders (>90%). The most commonly diagnosed conditions were developmental coordination disorder, phonologic processing disorder, expressive and receptive language disorders (71% of individuals >3 years old with a speech and language-related disorder), and autism spectrum disorder. Individuals with the 16p11.2 deletion not meeting diagnostic criteria for autism spectrum disorder had a significantly higher prevalence of autism-related characteristics compared with the familial noncarrier control group. Individuals with the 16p11.2 deletion had a range of intellectual ability, but IQ scores were 26 points lower than noncarrier family members on average.

Conclusions: Clinically referred individuals with the 16p11.2 deletion have high rates of psychiatric and developmental disorders and provide a genetically well-defined group to study the emergence of developmental difficulties, particularly associated with the broader autism phenotype.

Keywords: 16p11.2 Deletion; Autism; Autism spectrum disorder; Developmental disability; Genetics; Psychiatric diagnosis.

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Figures

**Figure 1**
Distribution of FSIQ scores by deletion status highlights a 1.8 SD decrement in scores in 16p11.2 deletion cases relative to non-carrier family members. Dotted vertical line represents cutoff value for intellectual disability.

See this image and copyright information in PMC

Comment in

Genotype-first analysis of the 16p11.2 deletion defines a new type of "autism".
Duyzend MH, Eichler EE. Duyzend MH, et al. Biol Psychiatry. 2015 May 1;77(9):769-71. doi: 10.1016/j.biopsych.2015.02.032. Epub 2015 Mar 2. Biol Psychiatry. 2015. PMID: 25843334 Free PMC article. No abstract available.

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The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population

Collaborators

Affiliations

The cognitive and behavioral phenotype of the 16p11.2 deletion in a clinically ascertained population

Authors

Collaborators

Affiliations

Abstract

Figures

Comment in

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical