Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

A case of follow-up of a patient with 22q11.2 distal deletion syndrome and a review of the literature

  • Ha, Dong Jun (Department of Pediatrics, Inha University Hospital, Inha University College of Medicine) ;
  • Park, Ji Sun (Department of Pediatrics, Inha University Hospital, Inha University College of Medicine) ;
  • Jang, Woori (Northwest Gyeonggi Regional Center for Rare Disease) ;
  • Jung, Na-young (Department of Pediatrics, Inha University Hospital, Inha University College of Medicine) ;
  • Kim, Su Jin (Department of Pediatrics, Inha University Hospital, Inha University College of Medicine) ;
  • Moon, Yeonsook (Northwest Gyeonggi Regional Center for Rare Disease) ;
  • Lee, Jieun (Department of Pediatrics, Inha University Hospital, Inha University College of Medicine)
  • Received : 2021.10.07
  • Accepted : 2021.11.08
  • Published : 2021.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Microdeletions of chromosome 22q11.2 are one of the most common microdeletions occurring in humans, and is known to be associated with a wide range of highly variable features. These deletions occur within a cluster of low copy repeats (LCRs) in 22q11.2, referred to as LCR22 A-H. DiGeorge (DGS)/velocardiofacial syndrome is the most prevalent form of a 22q11.2 deletions, caused by mainly proximal deletions between LCR22 A and D. As deletions of distal portion to the DGS deleted regions has been extensively studied, the recurrent distal 22q11.2 microdeletions distinct from DGS has been suggested as several clinical entities according to the various in size and position of the deletions on LCRs. We report a case of long-term follow-up of a female diagnosed with a 22q11.2 distal deletion syndrome, identified a deletion of 1.9 Mb at 22q11.21q11.23 (chr22: 21,798,906-23,653,963) using single nucleotide polymorphism array. This region was categorized as distal deletion type of 22q11.2, involving LCR22 D-F. She was born as a preterm, low birth weight to healthy non-consanguineous Korean parents. She showed developmental delay, growth retardation, dysmorphic facial features, and mild skeletal deformities. The patient underwent a growth hormone administration due to growth impairment without catch-up growth. While a height gain was noted, she had become overweight and was subsequently diagnosed with pre-diabetes. Our case could help broaden the genetic and clinical spectrum of 22q11.2 distal deletions.

Keywords

References

  1. Bailey JA, Eichler EE. Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet 2006;7:552-64. https://doi.org/10.1038/nrg1895
  2. Low copy repeats. In: Ganten D, Ruckpaul K, Birchmeier W, Epplen JT, Genser K, Gossen M, eds. Encyclopedic reference of genomics and proteomics in molecular medicine. Berlin-Heidelberg: Springer, 2006.
  3. Burnside RD. 22q11.21 Deletion syndromes: a review of proximal, central, and distal deletions and their associated features. Cytogenet Genome Res 2015;146:89-99. https://doi.org/10.1159/000438708
  4. UCSC Genome Browser on Human Feb. 2009 (GRCh37/hg19) Assembly [Internet]. Santa Cruz, CA: University of California, Santa Cruz, 2009. [http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr22%3A18000000%2D24500000&hgsid=1148663159_n9kWeMIHchvJUxiUTExIASCYbbL1]
  5. McDonald-McGinn DM, Kirschner R, Goldmuntz E, Sullivan K, Eicher P, Gerdes M, et al. The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns 1999;10:11-24.
  6. Blue Cross Blue Shield Asssociation. Special report: chromosomal microarray for the genetic evaluation of patients with global developmental delay, intellectual disability, and autism spectrum disorder. Technol Eval Cent Assess Program Exec Summ 2015;30:1-4.
  7. Rodningen OK, Prescott T, Eriksson AS, Rosby O. 1.4Mb recurrent 22q11.2 distal deletion syndrome, two new cases expand the phenotype. Eur J Med Genet 2008;51:646-50. https://doi.org/10.1016/j.ejmg.2008.07.007
  8. Molck MC, Vieira TP, Sgardioli IC, Simioni M, Dos Santos AP, Souza J, et al. Atypical copy number abnormalities in 22q11.2 region: report of three cases. Eur J Med Genet 2013;56:515-20. https://doi.org/10.1016/j.ejmg.2013.07.002
  9. Sgardioli IC, de Mello Copelli M, Monteiro FP, Dos Santos AP, Lustosa Mendes E, Paiva Vieira T, et al. Diagnostic approach to microdeletion syndromes based on 22q11.2 investigation: challenges in four cases. Mol Syndromol 2017;8:244-52. https://doi.org/10.1159/000477598
  10. Tan TY, Collins A, James PA, McGillivray G, Stark Z, Gordon CT, et al. Phenotypic variability of distal 22q11.2 copy number abnormalities. Am J Med Genet A 2011;155A:1623-33.
  11. Spineli-Silva S, Bispo LM, Gil-da-Silva-Lopes VL, Vieira TP. Distal deletion at 22q11.2 as differential diagnosis in craniofacial microsomia: case report and literature review. Eur J Med Genet 2018;61:262-8. https://doi.org/10.1016/j.ejmg.2017.12.013
  12. Mikhail FM, Burnside RD, Rush B, Ibrahim J, Godshalk R, Rutledge SL, et al. The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system. Genet Med 2014;16:92-100. https://doi.org/10.1038/gim.2013.79
  13. Aouadi M, Binetruy B, Caron L, Le Marchand-Brustel Y, Bost F. Role of MAPKs in development and differentiation: lessons from knockout mice. Biochimie 2006;88:1091-8. https://doi.org/10.1016/j.biochi.2006.06.003
  14. Kaufman CS, Genovese A, Butler MG. Deletion of TOP3B is associated with cognitive impairment and facial dysmorphism. Cytogenet Genome Res 2016;150:106-11. https://doi.org/10.1159/000452815
  15. Moon AM, Guris DL, Seo JH, Li L, Hammond J, Talbot A, et al. Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndromes. Dev Cell 2006;10:71-80. https://doi.org/10.1016/j.devcel.2005.12.003
  16. Tarquinio DC, Jones MC, Jones KL, Bird LM. Growth charts for 22q11 deletion syndrome. Am J Med Genet A 2012;158A:2672-81. https://doi.org/10.1002/ajmg.a.35485
  17. Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 1997;34:798-804. https://doi.org/10.1136/jmg.34.10.798
  18. Voll SL, Boot E, Butcher NJ, Cooper S, Heung T, Chow EW, et al. Obesity in adults with 22q11.2 deletion syndrome. Genet Med 2017;19:204-8. https://doi.org/10.1038/gim.2016.98
  19. Digilio MC, Marino B, Cappa M, Cambiaso P, Giannotti A, Dallapiccola B. Auxological evaluation in patients with DiGeorge/velocardiofacial syndrome (deletion 22q11.2 syndrome). Genet Med 2001;3:30-3. https://doi.org/10.1097/00125817-200101000-00007
  20. Bassett JK, Chandler KE, Douzgou S. Two patients with chromosome 22q11.2 deletion presenting with childhood obesity and hyperphagia. Eur J Med Genet 2016;59:401-3. https://doi.org/10.1016/j.ejmg.2016.05.008