Deletion of 2q22.2q22.3 in Mowat–Wilson Syndrome: A Case Report and Review of the Literature

Abstract

Mowat–Wilson syndrome (MWS; Online Mendelian Inheritance in Man #235730) is a rare disorder characterized by developmental delay, severe intellectual disability, distinctive facial dysmorphism, and multiple associated abnormalities caused by mutation or deletion of ZEB2 gene. Here we report a 13 months old boy with characteristic facial features of MWS, global developmental delay, peculiar behavior, microcephaly, and hypospadias. Array comparative genomic hybridization (CGH) revealed a 5.7-Mb deletion of 2q22.2q22.3 region. The deletion contains 10 genes, including LRP1B, KYNU, ARHGAP15, GTDC1, ZEB2, ZEB2-AS1, TEX41, MBD5, ORC4, and ACVR2A. Our case shows the utility of array CGH in identifying such complex phenotype.

Keywords

2q22.2q22.3 deletion - ZEB2 gene - chromosome microarray - hypospadias - developmental delay

Publication History

Received: 10 February 2022

Accepted: 20 April 2022

Article published online:
02 August 2022

• References

• 1 Mulatinho MV, de Carvalho Serao CL, Scalco F, Hardekopf D, Pekova S, Mrasek K. et al. Severe intellectual disability, omphalocele, hypospadia and high blood pressure associated to a deletion at 2q22.1q22.3: case report. Mol Cytogenet 2012; 5 (01) 30
• 2 Hoffer MJ, Hilhorst-Hofstee Y, Knijnenburg J. et al. A 6Mb deletion in band 2q22 due to a complex chromosome rearrangement associated with severe psychomotor retardation, microcephaly and distinctive dysmorphic facial features. Eur J Med Genet 2007; 50 (02) 149-154
• 3 Zweier C, Albrecht B, Mitulla B. et al. “Mowat-Wilson” syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene. Am J Med Genet 2002; 108 (03) 177-181
• 4 Park JY, Cho EH, Lee EH, Kang YS, Jun KR, Hur YJ. Mowat-Wilson syndrome detected by using high resolution microarray. Gene 2013; 532 (02) 307-309
• 5 Celep F, Sönmez FM, Karagüzel A. Chromosomal abnormalities in 457 Turkish patients with MCA/MR. Turk J Pediatr 2006; 48 (02) 130-134
• 6 Miller DT, Adam MP, Aradhya S. et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010; 86 (05) 749-764
• 7 Zweier C, Temple IK, Beemer F. et al. Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome. J Med Genet 2003; 40 (08) 601-605
• 8 Ishihara N, Yamada K, Yamada Y. et al. Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. J Med Genet 2004; 41 (05) 387-393
• 9 Lurie IW, Supovitz KR, Rosenblum-Vos LS, Wulfsberg EA. Phenotypic variability of del(2) (q22-q23): report of a case with a review of the literature. Genet Couns 1994; 5 (01) 11-14
• 10 Engenheiro E, Møller RS, Pinto M. et al. Mowat-Wilson syndrome: an underdiagnosed syndrome?. Clin Genet 2008; 73 (06) 579-584
• 11 Mowat DR, Croaker GD, Cass DT. et al. Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23. J Med Genet 1998; 35 (08) 617-623
• 12 Refaat K, Helmy N, Elawady M. et al. Interstitial deletion of 2q22.2q22.3 involving the entire ZEB2 gene in a case of Mowat-Wilson syndrome. Mol Syndromol 2021; 12 (02) 87-95
• 13 Garavelli L, Zollino M, Mainardi PC. et al. Mowat-Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature. Am J Med Genet A 2009; 149A [phone]
• 14 Ivanovski I, Djuric O, Caraffi SG. et al. Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care. Genet Med 2018; 20 (09) 965-975
• 15 Smigiel R, Szafranska A, Czyzewska M, Rauch A, Zweier Ch, Patkowski D. Severe clinical course of Hirschsprung disease in a Mowat-Wilson syndrome patient. J Appl Genet 2010; 51 (01) 111-113