Clinical and Cytogenomic Characterization of De Novo 11p14.3-p15.5 Duplication Associated with 18q23 Deletion in an Egyptian Female Infant

Abstract

Paternal microduplication of 11p14.3-p15.5 causes the clinical manifestations of Beckwith–Wiedemann syndrome (BWS), while microdeletion of 18q23-ter is clinically characterized by short stature, congenital malformations, and developmental delay. We describe a 15-month-old girl presenting with protruding tongue, dysmorphic facial features, moderate developmental delay, umbilical hernia, hypotonia, mild-to-moderate pulmonary hypertension, small patent ductus arteriosus, and mild ventricular septal hypertrophy. Brain magnetic resonance imaging showed mild atrophic changes. Chromosomal analysis revealed 46, XX, add(18)(q23). Fluorescence in situ hybridization using subtelomere 18q and whole chromosome painting 18 showed subtelomere deletion in 18q, and the add segment was not derived from chromosome 18. Microarray-based comparative genomic hybridization detected a 22 Mb duplication of chromosome 11p15.5p14.3 and a 3.7 Mb deletion of chromosome 18q23. The phenotype of the chromosomal rearrangements is probably resulted from a combination of dosage-sensitive genes. Our patient had clinical manifestations of both 18q deletion and BWS.

Keywords

chromosome 11p14.3-p15.5 duplication - associated chromosome 18q23-ter deletion - Beckwith–Wiedemann syndrome - microarray based comparative genomic hybridization - macroglossia

• References

• 1 Mussa A, Russo S, De Crescenzo A. et al. Prevalence of Beckwith-Wiedemann syndrome in North West of Italy. Am J Med Genet A 2013; 161A (10) 2481-2486
• 2 Barisic I, Boban L, Akhmedzhanova D. et al. Beckwith Wiedemann syndrome: A population-based study on prevalence, prenatal diagnosis, associated anomalies and survival in Europe. Eur J Med Genet 2018; 61 (09) 499-507
• 3 Duffy KA, Sajorda BJ, Yu AC. et al. Beckwith-Wiedemann syndrome in diverse populations. Am J Med Genet A 2019; 179 (04) 525-533
• 4 OMIM (Online Mendelian Inheritance in Man). 2019. Mc Kusick-Nathans Institute for Genetic Medicine, John Hopkins University (Baltiomore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). Accessed October 10, 2019 at: http://www.ncbi.nlm.nih.gov/omim/
• 5 Wangler MF, An P, Feinberg AP, Province M, Debaun MR. Inheritance pattern of Beckwith-Wiedemann syndrome is heterogeneous in 291 families with an affected proband. Am J Med Genet A 2005; 137 (01) 16-21
• 6 Brioude F, Kalish JM, Mussa A. et al. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol 2018; 14 (04) 229-249
• 7 Slavotinek A, Gaunt L, Donnai D. Paternally inherited duplications of 11p15.5 and Beckwith-Wiedemann syndrome. J Med Genet 1997; 34 (10) 819-826
• 8 Waziri M, Patil SR, Hanson JW, Bartley JA. Abnormality of chromosome 11 in patients with features of Beckwith-Wiedemann syndrome. J Pediatr 1983; 102 (06) 873-876
• 9 Eggermann T, Spengler S, Bachmann N. et al. Chromosome 11p15 duplication in Silver-Russell syndrome due to a maternally inherited translocation t(11;15). Am J Med Genet A 2010; 152A [phone]
• 10 Sabouni MA, Benedict D, Alom MS, Petty S, Patel K. Atrial septal defect can be easily missed in chromosome 18q deletion syndrome. Oxf Med Case Rep 2018; 2018 (10) omy076
• 11 El-Sady RS, El-Shoubary MA, Hafez GN, Mohammad AA. Standardization, Translation and Modification of the Preschool Language Scale-4 (Ph.D. dissertation)]. Faculty of Medicine, Ain Shams University; Cairo, Egypt: 2011
• 12 Delicado A, Lapunzina P, Palomares M, Molina MA, Galán E, López Pajares I. Beckwith-Wiedemann syndrome due to 11p15.5 paternal duplication associated with Klinefelter syndrome and a “de novo” pericentric inversion of chromosome Y. Eur J Med Genet 2005; 48 (02) 159-166
• 13 Han JY, Shin JH, Han MS, Je GH, Shaffer LG. Microarray detection of a de novo der(X)t(X;11)(q28;p13) in a girl with premature ovarian failure and features of Beckwith-Wiedemann syndrome. J Hum Genet 2006; 51 (07) 641-643
• 14 Mikhail FM, Sathienkijkanchai A, Robin NH. et al. Overlapping phenotype of Wolf-Hirschhorn and Beckwith-Wiedemann syndromes in a girl with der(4)t(4;11)(pter;pter). Am J Med Genet A 2007; 143A (15) 1760-1766
• 15 Brewer CM, Lam WW, Hayward C, Grace E, Maher ER, FitzPatrick DR. Beckwith-Wiedemann syndrome in a child with chromosome 18q deletion. J Med Genet 1998; 35 (02) 162-164
• 16 Lirussi F, Jonard L, Gaston V. et al. Beckwith-Wiedemann-like macroglossia and 18q23 haploinsufficiency. Am J Med Genet A 2007; 143A (23) 2796-2803
• 17 Linnankivi T, Tienari P, Somer M. et al. 18q deletions: clinical, molecular, and brain MRI findings of 14 individuals. Am J Med Genet A 2006; 140 (04) 331-339
• 18 Cody JD, Hasi M, Soileau B. et al. Establishing a reference group for distal 18q-: clinical description and molecular basis. Hum Genet 2014; 133 (02) 199-209
• 19 Feenstra I, Vissers LELM, Orsel M. et al. Genotype-phenotype mapping of chromosome 18q deletions by high-resolution array CGH: an update of the phenotypic map. Am J Med Genet A 2007; 143A (16) 1858-1867
• 20 Cody JD, Heard PL, Crandall AC. et al. Narrowing critical regions and determining penetrance for selected 18q- phenotypes. Am J Med Genet A 2009; 149A [phone]
• 21 Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet 2010; 18 (01) 8-14
• 22 Wang Q, Geng Q, Zhou Q, Luo F, Li P, Xie J. De novo paternal origin duplication of chromosome 11p15.5: report of two Chinese cases with Beckwith-Wiedemann syndrome. Mol Cytogenet 2017; 10: 46
• 23 Tobias JD, Lowe S, Holcomb III GW. Anesthetic considerations of an infant with Beckwith-Wiedemann syndrome. J Clin Anesth 1992; 4 (06) 484-486
• 24 Gardiner K, Chitayat D, Choufani S. et al. Brain abnormalities in patients with Beckwith-Wiedemann syndrome. Am J Med Genet A 2012; 158A [phone]
• 25 Kambouris M, Maroun RC, Ben-Omran T. et al. Mutations in zinc finger 407 [ZNF407] cause a unique autosomal recessive cognitive impairment syndrome. Orphanet J Rare Dis 2014; 9: 80
• 26 Sniekers S, Stringer S, Watanabe K. et al. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nat Genet 2017; 49 (07) 1107-1112
• 27 Cody JD, Heard P, Rupert D. et al. Chromosome 18 gene dosage map 2.0. Hum Genet 2018; 137 (11,12): 961-970