Cardiovascular findings in duplication 17p11.2 syndrome

Journal name:
Genetics in Medicine
Published online



Cardiovascular abnormalities are newly recognized features of duplication 17p11.2 syndrome. In a single-center study, we evaluated subjects with duplication 17p11.2 syndrome for cardiovascular abnormalities.


Twenty-five subjects with 17p11.2 duplication identified by chromosome analysis and/or array-based comparative genomic hybridization were enrolled in a multidisciplinary protocol. In our clinical evaluation of these subjects, we performed physical examinations, echocardiography, and electrocardiography. Three of these subjects were followed up longitudinally at our institution.


Cardiovascular anomalies, including structural and conduction abnormalities, were identified in 10 of 25 (40%) of subjects with duplication 17p11.2 syndrome. The most frequent abnormality was dilated aortic root (20% of total cohort). Bicommissural aortic valve (2/25), atrial (3/25) and ventricular (2/25) septal defects, and patent foramen ovale (4/25) were also observed.


Duplication 17p11.2 syndrome is associated with structural heart disease, aortopathy, and electrocardiographic abnormalities. Individuals with duplication 17p11.2 syndrome should be evaluated by electrocardiography and echocardiography at the time of diagnosis and monitored for cardiovascular disease over time. Further clinical investigation including longitudinal analysis would likely determine the age of onset and characterize the progression (if any) of vasculopathy in subjects with duplication 17p11.2 syndrome, so that specific guidelines can be established for cardiovascular management.

Genet Med 2012:14(1):90–94.


chromosome 17p duplication; congenital heart defects; dilated aortic root; Potocki-Lupski syndrome; PTLS; vasculopathy

At a glance


  1. Figure 1:

    Subject 2211 in a parasternal long-axis view, the dilatation of the aorta is observed in different segments. The aortic annulus diameter is the distance between 1 and 1 (Z score: 3.27); the aortic root diameter is the distance between 2 and 2 (Z score: 6.03); and the sinotubular junction is the distance between 3 and 3 (Z score: 9.06). Ao, aorta; LA, left atrium; LV, left ventricle; RV, right ventricle.

  2. Figure 2:

    Summary of duplication sizes. The position and size of the genomic rearrangements (red (duplication), blue (triplication), and green (deletion) bars), as determined by array CGH are depicted for each subject. An ideogram of chromosome 17p, with a scale indicating the genomic coordinates (version hg18), and the locations of PMP22 and RAI1 genes are also included. Subject 2343 (mosaic marker) is not shown. Cardiac phenotype of each patient with CHD is briefly summarized in Table 1 and detailed in the text. Modified with permission from Am J Hum Genet.3 CGH, comparative genomic hybridization; CHD, congenital heart defect.


  1. Potocki L, Bi W, Treadwell-Deering D, et al. Characterization of Potocki- Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet 2007;80:633649.
  2. Potocki L, Chen KS, Park SS, et al. Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. Nat Genet 2000;24:8487.
  3. Zhang F, Potocki L, Sampson JB, et al. Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS. Am J Hum Genet 2010;86:462470.
  4. Bi W, Park SS, Shaw CJ, Withers MA, Patel PI, Lupski JR. Reciprocal crossovers and a positional preference for strand exchange in recombination events resulting in deletion or duplication of chromosome 17p11.2. Am J Hum Genet 2003;73:13021315.
  5. Zhang F, Khajavi M, Connolly AM, Towne CF, Batish SD, Lupski JR. The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans. Nat Genet 2009;41:849853.
  6. Sanchez-Valle A, Pierpont ME, Potocki L. The severe end of the spectrum: Hypoplastic left heart in Potocki-Lupski syndrome. Am J Med Genet A 2011;155A:363366.
  7. Soler-Alfonso C, Motil KJ, Turk CL, et al. Potocki-Lupski syndrome: a microduplication syndrome associated with oropharyngeal dysphagia and failure to thrive. J Pediatr 2011;158:655659.e2.
  8. Yusupov R, Roberts AE, Lacro RV, Sandstrom M, Ligon AH. Potocki-Lupski syndrome: an inherited dup(17)(p11.2p11.2) with hypoplastic left heart. Am J Med Genet A 2011;155A:367371.
  9. Treadwell-Deering DE, Powell MP, Potocki L. Cognitive and behavioral characterization of the Potocki-Lupski syndrome (duplication 17p11.2). J Dev Behav Pediatr 2010;31:137143.
  10. Yatsenko SA, Treadwell-Deering D, Krull K, et al. Trisomy 17p10-p12 due to mosaic supernumerary marker chromosome: delineation of molecular breakpoints and clinical phenotype, and comparison to other proximal 17p segmental duplications. Am J Med Genet A 2005;138A:175180.
  11. Lai WW, Geva T, Shirali GS, et al. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. J Am Soc Echocardiogr 2006;19:14131430.
  12. Sluysmans T, Colan SD. Theoretical and empirical derivation of cardiovascular allometric relationships in children. J Appl Physiol 2005;99:445457.
  13. Girirajan S, Williams SR, Garbern JY, Nowak N, Hatchwell E, Elsea SH. 17p11.2p12 triplication and del(17)q11.2q12 in a severely affected child with dup(17)p11.2p12 syndrome. Clin Genet 2007;72:4758.
  14. Kaplan S. Congenital heart disease in adolescents and adults. Natural and postoperative history across age groups. Cardiol Clin 1993;11:543556.
  15. Wu MH, Chen HC, Lu CW, Wang JK, Huang SC, Huang SK. Prevalence of congenital heart disease at live birth in Taiwan. J Pediatr 2010;156: 782785.
  16. Yan J, Bi W, Lupski JR. Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. Am J Hum Genet 2007;80:518525.
  17. Yan J, Keener VW, Bi W, et al. Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome. Hum Mol Genet 2004;13:26132624.
  18. Lupski JR. Genomic disorders ten years on. Genome Med 2009;1:42.

Download references

Author information


  1. Section of Pediatric Cardiology, Texas Children’s Hospital, Houston, Texas, USA

    • John L. Jefferies &
    • Hugo R. Martinez
  2. Division of Adult Cardiovascular Diseases, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas, USA

    • John L. Jefferies
  3. Department of Pediatrics, Texas Children’s Hospital, Houston, Texas, USA

    • Ricardo H. Pignatelli &
    • James R. Lupski
  4. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

    • Patricia J. Robbins-Furman,
    • Pengfei Liu,
    • Wenli Gu,
    • James R. Lupski &
    • Lorraine Potocki

Corresponding author

Correspondence to:

Author details

Supplementary information

Word documents

  1. Supplementary Data (60K)

Additional data