16p11.2 duplication is a chromosomal change in which a small amount of genetic material within chromosome 16 is abnormally copied (duplicated). The duplication occurs near the middle of the chromosome at a location designated p11.2. This duplication can have a variety of effects. Common characteristics that occur in people with a 16p11.2 duplication include a low weight; a small head size (microcephaly); and developmental delay, especially in speech and language. Affected individuals also have an increased risk of behavioral problems. However, some people with the duplication have no identified physical or behavioral abnormalities.

Developmental delay and intellectual disability can occur in people with a 16p11.2 duplication. Approximately one-third of children with this condition have delays in developing physical skills such as sitting, crawling, or walking. The average IQ of affected individuals is about 26 points lower than that of their parents without the duplication. About 80 percent of people with a 16p11.2 duplication have problems related to speech or language. Both expressive language skills (vocabulary and the production of speech) and receptive language skills (the ability to understand speech) can be affected.

One of the most common behavioral problems associated with this chromosomal change is attention-deficit/hyperactivity disorder (ADHD). Autism spectrum disorder, which affects communication and social skills, is diagnosed in about one in five people with a 16p11.2 duplication. Affected individuals also have an increased risk of mental health problems, including schizophrenia, anxiety, and depression. Recurrent seizures are possible in this condition, although they do not occur in most affected individuals.

Other abnormalities that can occur with a 16p11.2 duplication include malformations of the kidneys and urinary tract. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 duplications; signs and symptoms related to the chromosomal change vary even among affected members of the same family.

16p11.2 duplications have been estimated to occur in about 3 in 10,000 people. These changes are present in about 4 in 10,000 people who have mental health problems or difficulties with speech and language. Many people with the duplication are likely never diagnosed because there are many causes of these problems, and some people with the duplication have no related health or developmental problems.

People with a 16p11.2 duplication have an extra copy of a segment of genetic material on the short (p) arm of chromosome 16 at a position known as p11.2. This duplication affects one of the two copies of chromosome 16 in each cell. The length of the duplicated segment is most often about 600,000 DNA building blocks (base pairs), also written as 600 kilobases (kb). The 600 kb region contains more than 25 genes, and little is known about the function of most of these genes. Researchers are working to determine how the extra genetic material contributes to the features of 16p11.2 duplication.

Genetic Testing Information

• Genetic Testing Registry: Chromosome 16p11.2 duplication syndrome

Genetic and Rare Diseases Information Center

• Proximal 16p11.2 microduplication syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• CHROMOSOME 16p11.2 DUPLICATION SYNDROME

Scientific Articles on PubMed

• PubMed

• D'Angelo D, Lebon S, Chen Q, Martin-Brevet S, Snyder LG, Hippolyte L, Hanson E, Maillard AM, Faucett WA, Mace A, Pain A, Bernier R, Chawner SJ, David A, Andrieux J, Aylward E, Baujat G, Caldeira I, Conus P, Ferrari C, Forzano F, Gerard M, Goin-Kochel RP, Grant E, Hunter JV, Isidor B, Jacquette A, Jonch AE, Keren B, Lacombe D, Le Caignec C, Martin CL, Mannik K, Metspalu A, Mignot C, Mukherjee P, Owen MJ, Passeggeri M, Rooryck-Thambo C, Rosenfeld JA, Spence SJ, Steinman KJ, Tjernagel J, Van Haelst M, Shen Y, Draganski B, Sherr EH, Ledbetter DH, van den Bree MB, Beckmann JS, Spiro JE, Reymond A, Jacquemont S, Chung WK; Cardiff University Experiences of Children With Copy Number Variants (ECHO) Study; 16p11.2 European Consortium; Simons Variation in Individuals Project (VIP) Consortium. Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities. JAMA Psychiatry. 2016 Jan;73(1):20-30. doi: 10.1001/jamapsychiatry.2015.2123. Citation on PubMed
• Fernandez BA, Roberts W, Chung B, Weksberg R, Meyn S, Szatmari P, Joseph-George AM, Mackay S, Whitten K, Noble B, Vardy C, Crosbie V, Luscombe S, Tucker E, Turner L, Marshall CR, Scherer SW. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet. 2010 Mar;47(3):195-203. doi: 10.1136/jmg.2009.069369. Epub 2009 Sep 15. Citation on PubMed
• Filges I, Sparagana S, Sargent M, Selby K, Schlade-Bartusiak K, Lueder GT, Robichaux-Viehoever A, Schlaggar BL, Shimony JS, Shinawi M. Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication. Am J Med Genet A. 2014 Aug;164A(8):2003-12. doi: 10.1002/ajmg.a.36605. Epub 2014 May 28. Citation on PubMed
• Jacquemont S, Reymond A, Zufferey F, Harewood L, Walters RG, Kutalik Z, Martinet D, Shen Y, Valsesia A, Beckmann ND, Thorleifsson G, Belfiore M, Bouquillon S, Campion D, de Leeuw N, de Vries BB, Esko T, Fernandez BA, Fernandez-Aranda F, Fernandez-Real JM, Gratacos M, Guilmatre A, Hoyer J, Jarvelin MR, Kooy RF, Kurg A, Le Caignec C, Mannik K, Platt OS, Sanlaville D, Van Haelst MM, Villatoro Gomez S, Walha F, Wu BL, Yu Y, Aboura A, Addor MC, Alembik Y, Antonarakis SE, Arveiler B, Barth M, Bednarek N, Bena F, Bergmann S, Beri M, Bernardini L, Blaumeiser B, Bonneau D, Bottani A, Boute O, Brunner HG, Cailley D, Callier P, Chiesa J, Chrast J, Coin L, Coutton C, Cuisset JM, Cuvellier JC, David A, de Freminville B, Delobel B, Delrue MA, Demeer B, Descamps D, Didelot G, Dieterich K, Disciglio V, Doco-Fenzy M, Drunat S, Duban-Bedu B, Dubourg C, El-Sayed Moustafa JS, Elliott P, Faas BH, Faivre L, Faudet A, Fellmann F, Ferrarini A, Fisher R, Flori E, Forer L, Gaillard D, Gerard M, Gieger C, Gimelli S, Gimelli G, Grabe HJ, Guichet A, Guillin O, Hartikainen AL, Heron D, Hippolyte L, Holder M, Homuth G, Isidor B, Jaillard S, Jaros Z, Jimenez-Murcia S, Helas GJ, Jonveaux P, Kaksonen S, Keren B, Kloss-Brandstatter A, Knoers NV, Koolen DA, Kroisel PM, Kronenberg F, Labalme A, Landais E, Lapi E, Layet V, Legallic S, Leheup B, Leube B, Lewis S, Lucas J, MacDermot KD, Magnusson P, Marshall C, Mathieu-Dramard M, McCarthy MI, Meitinger T, Mencarelli MA, Merla G, Moerman A, Mooser V, Morice-Picard F, Mucciolo M, Nauck M, Ndiaye NC, Nordgren A, Pasquier L, Petit F, Pfundt R, Plessis G, Rajcan-Separovic E, Ramelli GP, Rauch A, Ravazzolo R, Reis A, Renieri A, Richart C, Ried JS, Rieubland C, Roberts W, Roetzer KM, Rooryck C, Rossi M, Saemundsen E, Satre V, Schurmann C, Sigurdsson E, Stavropoulos DJ, Stefansson H, Tengstrom C, Thorsteinsdottir U, Tinahones FJ, Touraine R, Vallee L, van Binsbergen E, Van der Aa N, Vincent-Delorme C, Visvikis-Siest S, Vollenweider P, Volzke H, Vulto-van Silfhout AT, Waeber G, Wallgren-Pettersson C, Witwicki RM, Zwolinksi S, Andrieux J, Estivill X, Gusella JF, Gustafsson O, Metspalu A, Scherer SW, Stefansson K, Blakemore AI, Beckmann JS, Froguel P. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature. 2011 Aug 31;478(7367):97-102. doi: 10.1038/nature10406. Citation on PubMed or Free article on PubMed Central
• McCarthy SE, Makarov V, Kirov G, Addington AM, McClellan J, Yoon S, Perkins DO, Dickel DE, Kusenda M, Krastoshevsky O, Krause V, Kumar RA, Grozeva D, Malhotra D, Walsh T, Zackai EH, Kaplan P, Ganesh J, Krantz ID, Spinner NB, Roccanova P, Bhandari A, Pavon K, Lakshmi B, Leotta A, Kendall J, Lee YH, Vacic V, Gary S, Iakoucheva LM, Crow TJ, Christian SL, Lieberman JA, Stroup TS, Lehtimaki T, Puura K, Haldeman-Englert C, Pearl J, Goodell M, Willour VL, Derosse P, Steele J, Kassem L, Wolff J, Chitkara N, McMahon FJ, Malhotra AK, Potash JB, Schulze TG, Nothen MM, Cichon S, Rietschel M, Leibenluft E, Kustanovich V, Lajonchere CM, Sutcliffe JS, Skuse D, Gill M, Gallagher L, Mendell NR; Wellcome Trust Case Control Consortium; Craddock N, Owen MJ, O'Donovan MC, Shaikh TH, Susser E, Delisi LE, Sullivan PF, Deutsch CK, Rapoport J, Levy DL, King MC, Sebat J. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet. 2009 Nov;41(11):1223-7. doi: 10.1038/ng.474. Epub 2009 Oct 25. Citation on PubMed or Free article on PubMed Central
• Rosenfeld JA, Coppinger J, Bejjani BA, Girirajan S, Eichler EE, Shaffer LG, Ballif BC. Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications. J Neurodev Disord. 2010 Mar;2(1):26-38. doi: 10.1007/s11689-009-9037-4. Citation on PubMed or Free article on PubMed Central
• Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, Scott DA, Probst FJ, Craigen WJ, Graham BH, Pursley A, Clark G, Lee J, Proud M, Stocco A, Rodriguez DL, Kozel BA, Sparagana S, Roeder ER, McGrew SG, Kurczynski TW, Allison LJ, Amato S, Savage S, Patel A, Stankiewicz P, Beaudet AL, Cheung SW, Lupski JR. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010 May;47(5):332-41. doi: 10.1136/jmg.2009.073015. Epub 2009 Nov 12. Citation on PubMed or Free article on PubMed Central
• Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, Saemundsen E, Stefansson H, Ferreira MA, Green T, Platt OS, Ruderfer DM, Walsh CA, Altshuler D, Chakravarti A, Tanzi RE, Stefansson K, Santangelo SL, Gusella JF, Sklar P, Wu BL, Daly MJ; Autism Consortium. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008 Feb 14;358(7):667-75. doi: 10.1056/NEJMoa075974. Epub 2008 Jan 9. Citation on PubMed