22q11.2 Microduplication: An Enigmatic Genetic Disorder

Abstract

Microduplication of 22q11.2 involves having an extra copy at position q11.2 on chromosome 22. Very few cases have been reported but the real incidence may be higher as the absence of obvious clinical signs makes diagnosis difficult. In the cases that are diagnosed, the phenotype is extremely variable. We describe a case of severe micrognathia, cleft palate, and Pierre-Robin sequence. A prenatal ultrasound showed severe micrognathia and subsequent microarray done on amniocentesis revealed the microduplication of 22q11.2, which was confirmed postnatally. Although micrognathia has often been detected in this microduplication, the constellation of these findings has not been previously described.

Keywords

22q11.2 microdeletion - 22q11.2 microduplication - micrognathia - cleft palate - Pierre-Robin sequence

Additional Note

Full consent was obtained from the patient's parents for the case report. Research and ethics board approval has been obtained.

• References

• 1 Firth' HV. 22q11.2 Duplication. 2009 Feb 17 [updated 2013 Nov 21]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mefford HC, Stephens K, Amemiya A, Ledbetter N. , editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017 . Available at: http://www.ncbi.nlm.nih.gov/books/NBK3823/ PubMed PMID: 20301749. Accessed January 2, 2018.
• 2 Van Campenhout S, Devriendt K, Breckpot J. , et al. Microduplication 22q11.2: a description of the clinical, developmental and behavioral characteristics during childhood. Genet Couns 2012; 23 (02) 135-148
• 3 Edelmann L, Pandita RK, Spiteri E. , et al. A common molecular basis for rearrangement disorders on chromosome 22q11. Hum Mol Genet 1999; 8 (07) 1157-1167
• 4 Ensenauer RE, Adeyinka A, Flynn HC. , et al. Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients. Am J Hum Genet 2003; 73 (05) 1027-1040
• 5 Stachon AC, Baskin B, Smith AC. , et al. Molecular diagnosis of 22q11.2 deletion and duplication by multiplex ligation dependent probe amplification. Am J Med Genet A 2007; 143A (24) 2924-2930
• 6 Pinchefsky E, Laneuville L, Srour M. Distal 22q11.2 microduplication: case report and review of the literature. Child Neurol Open 2017; 4: 2329048-X17737651
• 7 Ou Z, Berg JS, Yonath H. , et al. Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes. Genet Med 2008; 10 (04) 267-277
• 8 Wentzel C, Fernström M, Ohrner Y, Annerén G, Thuresson AC. Clinical variability of the 22q11.2 duplication syndrome. Eur J Med Genet 2008; 51 (06) 501-510
• 9 Nguyen LT, Fleishman R, Flynn E. , et al. 22q11.2 microduplication syndrome with associated esophageal atresia/tracheo-esophageal fistula and vascular ring. Clin Case Rep 2017; 5 (03) 351-356
• 10 Puvabanditsin S, Garrow E, February M, Yen E, Mehta R. Esophageal atresia with recurrent tracheoesophageal fistulas and microduplication 22q11.23. Genet Couns 2015; 26 (03) 313-320
• 11 Schramm C, Draaken M, Bartels E. , et al. De novo microduplication at 22q11.21 in a patient with VACTERL association. Eur J Med Genet 2011; 54 (01) 9-13
• 12 Cordovez JA, Capasso J, Lingao MD. , et al. Ocular manifestations of 22q11.2 microduplication. Ophthalmology 2014; 121 (01) 392-398
• 13 Kim HJ, Jo HS, Yoo EG. , et al. 22q11.2 microduplication with thyroid hemiagenesis. Horm Res Paediatr 2013; 79 (04) 243-249
• 14 Wincent J, Bruno DL, van Bon BW. , et al. Sixteen new cases contributing to the characterization of patients with distal 22q11.2 microduplications. Mol Syndromol 2010; 1 (05) 246-254
• 15 Sedghi M, Abdali H, Memarzadeh M. , et al. Identification of proximal and distal 22q11.2 microduplications among patients with cleft lip and/or palate: a novel inherited atypical 0.6 Mb duplication. Genet Res Int 2015; 2015 (15) 398063
• 16 Wenger TL, Miller JS, DePolo LM. , et al. 22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening. Mol Autism 2016; 7: 27
• 17 Clements CC, Wenger TL, Zoltowski AR. , et al. Critical region within 22q11.2 linked to higher rate of autism spectrum disorder. Mol Autism 2017; 8: 58
• 18 Hoeffding LK, Trabjerg BB, Olsen L. , et al. Risk of psychiatric disorders among individuals with the 22q11.2 deletion or duplication: a Danish nationwide, register-based study. JAMA Psychiatry 2017; 74 (03) 282-290
• 19 van Amelsvoort T, Denayer A, Boermans J, Swillen A. Psychotic disorder associated with 22q11.2 duplication syndrome. Psychiatry Res 2016; 236: 206-207
• 20 Rees E, Kirov G, Sanders A. , et al; Wellcome Trust Case Control Consortium. Evidence that duplications of 22q11.2 protect against schizophrenia. Mol Psychiatry 2014; 19 (01) 37-40
• 21 Brunet A, Armengol L, Pelaez T. , et al. Failure to detect the 22q11.2 duplication syndrome rearrangement among patients with schizophrenia. Behav Brain Funct 2008; 4: 10
• 22 Ribeiro-Bicudo LA, de Campos Legnaro C, Gamba BF, Candido Sandri RM, Richieri-Costa A. Cognitive deficit, learning difficulties, severe behavioral abnormalities and healed cleft lip in a patient with a 1.2-mb distal microduplication at 22q11.2. Mol Syndromol 2013; 4 (06) 292-296
• 23 Weisfeld-Adams JD, Edelmann L, Gadi IK, Mehta L. Phenotypic heterogeneity in a family with a small atypical microduplication of chromosome 22q11.2 involving TBX1. Eur J Med Genet 2012; 55 (12) 732-736
• 24 de La Rochebrochard C, Joly-Hélas G, Goldenberg A. , et al. The intrafamilial variability of the 22q11.2 microduplication encompasses a spectrum from minor cognitive deficits to severe congenital anomalies. Am J Med Genet A 2006; 140 (14) 1608-1613
• 25 Yobb TM, Somerville MJ, Willatt L. , et al. Microduplication and triplication of 22q11.2: a highly variable syndrome. Am J Hum Genet 2005; 76 (05) 865-876
• 26 Wapner RJ, Martin CL, Levy B. , et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012; 367 (23) 2175-2184