17q12 duplication

17q12 duplication is a chromosomal change in which a small piece of chromosome 17 is copied (duplicated) abnormally in each cell. The duplication occurs on the long (q) arm of the chromosome at a position designated q12.

Signs and symptoms related to 17q12 duplications vary significantly, even among members of the same family. Some individuals with the duplication have no apparent signs or symptoms, or the features are very mild. Other individuals can have intellectual disability, delayed development, and a wide range of physical abnormalities.

Intellectual and learning ability in people with 17q12 duplications ranges from normal to severely impaired. Many affected individuals have delayed development, particularly involving speech and language skills and gross motor skills such sitting, standing, and walking. Seizures are also common. Neurodevelopmental and psychiatric conditions that have been reported in people with 17q12 duplications include autism spectrum disorder (which affects social interaction and communication), schizophrenia, aggression, and self-injury. About half of affected individuals have an unusually small head (microcephaly).

Less commonly, 17q12 duplications have been associated with abnormalities of the eyes, heart, kidneys, and brain. Some individuals with this chromosomal change have subtle differences in facial features, although these are not consistent.

17q12 duplications appear to be uncommon. Several dozen people with this chromosomal change have been described in the medical literature.

Most people with 17q12 duplications have an extra copy of about 1.4 million DNA building blocks (base pairs), also written as 1.4 megabases (Mb), at position q12 on chromosome 17. This duplication affects one of the two copies of chromosome 17 in each cell.

The duplicated segment is surrounded by short, repeated sequences of DNA that make the segment prone to rearrangement during cell division. The rearrangement can lead to extra or missing copies of DNA at 17q12. (A missing copy of this segment causes a related chromosomal condition called 17q12 deletion syndrome.)

The segment of 17q12 that is most commonly duplicated includes at least 15 genes. It is unclear which of these genes, when present in more than one copy, contribute to intellectual disability, delayed development, and the other signs and symptoms described above. Because some people with a 17q12 duplication have no obvious intellectual or physical problems, researchers suspect that additional genetic factors may influence whether a person has signs and symptoms related to the chromosomal change.

Genetic Testing Information

• Genetic Testing Registry: Chromosome 17q12 duplication syndrome

Genetic and Rare Diseases Information Center

• 17q12 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 17q12 DUPLICATION SYNDROME

Scientific Articles on PubMed

• PubMed

• Bertini V, Orsini A, Bonuccelli A, Cambi F, Del Pistoia M, Vannozzi I, Toschi B, Saggese G, Simi P, Valetto A. 17q12 microduplications: a challenge for clinicians. Am J Med Genet A. 2015 Mar;167A(3):674-6. doi: 10.1002/ajmg.a.36905. Citation on PubMed
• Bierhals T, Maddukuri SB, Kutsche K, Girisha KM. Expanding the phenotype associated with 17q12 duplication: case report and review of the literature. Am J Med Genet A. 2013 Feb;161A(2):352-9. doi: 10.1002/ajmg.a.35730. Epub 2013 Jan 10. Citation on PubMed
• Mefford H. 17q12 Recurrent Duplication. 2016 Feb 25 [updated 2022 Jan 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK344340/ Citation on PubMed
• Mefford HC, Clauin S, Sharp AJ, Moller RS, Ullmann R, Kapur R, Pinkel D, Cooper GM, Ventura M, Ropers HH, Tommerup N, Eichler EE, Bellanne-Chantelot C. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am J Hum Genet. 2007 Nov;81(5):1057-69. doi: 10.1086/522591. Epub 2007 Sep 26. Citation on PubMed or Free article on PubMed Central
• Mitchell E, Douglas A, Kjaegaard S, Callewaert B, Vanlander A, Janssens S, Yuen AL, Skinner C, Failla P, Alberti A, Avola E, Fichera M, Kibaek M, Digilio MC, Hannibal MC, den Hollander NS, Bizzarri V, Renieri A, Mencarelli MA, Fitzgerald T, Piazzolla S, van Oudenhove E, Romano C, Schwartz C, Eichler EE, Slavotinek A, Escobar L, Rajan D, Crolla J, Carter N, Hodge JC, Mefford HC. Recurrent duplications of 17q12 associated with variable phenotypes. Am J Med Genet A. 2015 Dec;167A(12):3038-45. doi: 10.1002/ajmg.a.37351. Epub 2015 Sep 30. Citation on PubMed
• Nagamani SC, Erez A, Shen J, Li C, Roeder E, Cox S, Karaviti L, Pearson M, Kang SH, Sahoo T, Lalani SR, Stankiewicz P, Sutton VR, Cheung SW. Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12. Eur J Hum Genet. 2010 Mar;18(3):278-84. doi: 10.1038/ejhg.2009.174. Epub 2009 Oct 21. Citation on PubMed or Free article on PubMed Central
• Rasmussen M, Vestergaard EM, Graakjaer J, Petkov Y, Bache I, Fagerberg C, Kibaek M, Svaneby D, Petersen OB, Brasch-Andersen C, Sunde L. 17q12 deletion and duplication syndrome in Denmark-A clinical cohort of 38 patients and review of the literature. Am J Med Genet A. 2016 Nov;170(11):2934-2942. doi: 10.1002/ajmg.a.37848. Epub 2016 Jul 13. Citation on PubMed
• Sharp AJ, Hansen S, Selzer RR, Cheng Z, Regan R, Hurst JA, Stewart H, Price SM, Blair E, Hennekam RC, Fitzpatrick CA, Segraves R, Richmond TA, Guiver C, Albertson DG, Pinkel D, Eis PS, Schwartz S, Knight SJ, Eichler EE. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet. 2006 Sep;38(9):1038-42. doi: 10.1038/ng1862. Epub 2006 Aug 13. Citation on PubMed