De Novo Inverted Duplication Deletion of 4p in a 14-Week-Old Male Fetus Aborted Due to Multiple Anomalies

Abstract

Inverted duplications deletions are rare, complex, and nonrecurrent chromosomal rearrangements associated with a variable phenotype. In this case report, we described the phenotype and genotype of a 14-week-old male fetus, who was aborted after discovery of multiple anomalies (septal cystic hygroma, open abdominal wall, and a nonidentifiable lower limb). At autopsy, fluorescence in situ hybridization and array comparative genomic hybridization identified an inverted duplication with terminal deletion of 4p [46,XY,der(4)del(p16.3)dup(4)(p15.2p16.3)]. Only five genotypically similar cases have been reported, and we hope our case contribution will add meaningful to the body of knowledge.

Keywords

inv dup del - 4p - gastroschisis - agenesis - lung hypoplasia

Publication History

Received: 14 February 2020

Accepted: 07 May 2020

Article published online:
19 June 2020

• References

• 1 Dill FJ, Schertzer M, Sandercock J, Tischler B, Wood S. Inverted tandem duplication generates a duplication deficiency of chromosome 8p. Clin Genet 1987; 32 (02) 109-113
• 2 Ballif BC, Yu W, Shaw CA, Kashork CD, Shaffer LG. Monosomy 1p36 breakpoint junctions suggest pre-meiotic breakage-fusion-bridge cycles are involved in generating terminal deletions. Hum Mol Genet 2003; 12 (17) 2153-2165
• 3 Van Dyke D. . Isochromosomes and interstitial tandem direct and inverted duplications. In: Daniel A. ed. The Cytogenetics of Mammalian Autosomal Rearrangements. New York: Alan R Liss; 1988: 635-665
• 4 Giglio S, Broman KW, Matsumoto N. et al. Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements. Am J Hum Genet 2001; 68 (04) 874-883
• 5 Zuffardi O, Bonaglia M, Ciccone R, Giorda R. Inverted duplications deletions: underdiagnosed rearrangements??. Clin Genet 2009; 75 (06) 505-513
• 6 Gu W, Zhang F, Lupski JR. Mechanisms for human genomic rearrangements. PathoGenetics 2008; 1 (01) 4
• 7 Lieber MR. The mechanism of human nonhomologous DNA end joining. J Biol Chem 2008; 283 (01) 1-5
• 8 Tanaka H, Cao Y, Bergstrom DA, Kooperberg C, Tapscott SJ, Yao MC. Intrastrand annealing leads to the formation of a large DNA palindrome and determines the boundaries of genomic amplification in human cancer. Mol Cell Biol 2007; 27 (06) 1993-2002
• 9 Daniel A, St Heaps L, Sylvester D, Diaz S, Peters G. Two mosaic terminal inverted duplications arising post-zygotically: evidence for possible formation of neo-telomeres. Cell Chromosome 2008; 7: 1
• 10 Cotter PD, Kaffe S, Li L, Gershin IF, Hirschhorn K. Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4. Am J Med Genet 2001; 102 (01) 76-80
• 11 Kondoh Y, Toma T, Ohashi H. et al. Inv dup del(4)(:p14 --> p16.3:p16.3 --> qter) with manifestations of partial duplication 4p and Wolf-Hirschhorn syndrome. Am J Med Genet A 2003; 120A [phone]
• 12 Beaujard M-P, Jouannic JM, Bessières B. et al. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype. Prenat Diagn 2005; 25 (06) 451-455
• 13 Paskulin GA, Riegel M, Cotter PD. et al. Inv dup del(4)(:p13-->p16.3:p16.3-->qter) in a girl without typical manifestations of Wolf-Hirschhorn syndrome. Am J Med Genet A 2009; 149A [phone]
• 14 Roselló M, Monfort S, Orellana C. et al. Submicroscopic duplication of the Wolf-Hirschhorn critical region with a 4p terminal deletion. Cytogenet Genome Res 2009; 125 (02) 103-108
• 15 Stembalska A, Laczmanska I, Schlade-Bartusiak K, Czemarmazowicz H, Murawski M, Sasiadek M. Recombinant chromosome 4 resulting from a maternal pericentric inversion in two sisters presenting consistent dysmorphic features. Eur J Pediatr 2007; 166 (01) 67-71
• 16 Zollino M, Lecce R, Fischetto R. et al. Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2. Am J Hum Genet 2003; 72 (03) 590-597
• 17 Rodríguez L, Zollino M, Climent S. et al. The new Wolf-Hirschhorn syndrome critical region (WHSCR-2): a description of a second case. Am J Med Genet A 2005; 136 (02) 175-178
• 18 Battaglia A, Filippi T, Carey JC. Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. Am J Med Genet C Semin Med Genet 2008; 148C [phone]
• 19 Bernardini L, Radio FC, Acquaviva F. et al. Small 4p16.3 deletions: Three additional patients and review of the literature. Am J Med Genet A 2018; 176 (11) 2501-2508
• 20 Meloni A, Shepard RR, Battaglia A, Wright TJ, Carey JC. Wolf-Hirschhorn syndrome: correlation between cytogenetics, FISH, and severity of disease. Am J Hum Genet 2000; 67: 149
• 21 Zollino M, Orteschi D, Ruiter M. et al. Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf-Hirschhorn syndrome-associated seizures disorder. Epilepsia 2014; 55 (06) 849-857
• 22 Coleman PK. Diagnosis of fetal anomaly and the increased maternal psychological toll associated with pregnancy termination. Issues Law Med 2015; 30 (01) 3-23
• 23 Hoeldtke NJ, Calhoun BC. Perinatal hospice. Am J Obstet Gynecol 2001; 185 (03) 525-529