Download PDF
J Pediatr Genet 2024; 13(04): 320-325
DOI: 10.1055/s-0042-1757621
Case-Based Review

A Patient Diagnosed with Mosaic Trisomy 18 Presenting New Symptoms: Diaphragmatic Relaxation and Cyclic Vomiting Syndrome. Updated Review of Mosaic Trisomy 18 Cases

Magdolna Kósa 
1   Department of Pediatrics and Pediatric Health Center, Albert Szent-Györgyi Health Centre, University of Szeged, Szeged, Hungary
,
Emese Horváth
2   Department of Medical Genetics, Albert Szent-Györgyi Health Centre, University of Szeged, Szeged, Hungary
,
Tibor Kalmár 
1   Department of Pediatrics and Pediatric Health Center, Albert Szent-Györgyi Health Centre, University of Szeged, Szeged, Hungary
,
Zoltán Maróti 
1   Department of Pediatrics and Pediatric Health Center, Albert Szent-Györgyi Health Centre, University of Szeged, Szeged, Hungary
,
Imre Földesi
3   Department of Laboratory Medicine, Albert Szent-Györgyi Health Centre, University of Szeged, Szeged, Hungary
,
Csaba Bereczki
1   Department of Pediatrics and Pediatric Health Center, Albert Szent-Györgyi Health Centre, University of Szeged, Szeged, Hungary
› Author Affiliations Funding This study was supported by the GINOP-2.3.2-15-2 grant (to T.K. and Z.M.) provided by the National Research, Development and Innovation Office (Hungary). The state funders had played no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Although data on T18 are widespread, there is a lack of knowledge on mosaic trisomy 18 (mT18). A current review of mT18 symptomatology, long-term follow-up, and potential health risks is lacking for health care professionals. Our paper addresses these, emphasizing the importance of regular tumor screening as a key message for mT18 patient follow-up. We also present the case of a female patient with mT18 who presented with diaphragmatic relaxation and cyclic vomiting syndrome (CVS), which had previously not been reported in this genetic condition. On further investigating the etiology of CVS, we revealed a novel mitochondrial mutation in the MT-ND6 gene in heteroplasmic form. Based on the literature, we hypothesize that the mitochondrial mutation together with mT18 could result in CVS.

Keywords

mosaic trisomy 18 - follow-up - cyclic vomiting syndrome - MT-ND6 mutation - diaphragmatic relaxation

Ethical Approval

The retrospective study was approved by the Human Investigation Board, University of Szeged, Hungary (208/2018-SZTE).


Supplementary Material



Publication History

Received: 07 June 2021

Accepted: 31 August 2022

Article published online:
01 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Carey JC. Trisomy 18 and trisomy 13 syndromes. In: John C. Carey AB, David Viskochil, Suzanne B. Cassidy, eds. Cassidy and Allanson's Management of Genetic Syndromes. 4th ed. John Wiley & Sons, Inc.; 2021
    Search in Google Scholar
  • 2 Tucker ME, Garringer HJ, Weaver DD. Phenotypic spectrum of mosaic trisomy 18: two new patients, a literature review, and counseling issues. Am J Med Genet A 2007; 143A (05) 505-517
    CrossrefPubMedSearch in Google Scholar
  • 3 van Oven M, Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 2009; 30 (02) E386-E394
    CrossrefPubMedSearch in Google Scholar
  • 4 McCoy RC. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet 2017; 33 (07) 448-463
    CrossrefPubMedSearch in Google Scholar
  • 5 Mantikou E, Wong KM, Repping S, Mastenbroek S. Molecular origin of mitotic aneuploidies in preimplantation embryos. Biochim Biophys Acta 2012; 1822 (12) 1921-1930
    CrossrefPubMedSearch in Google Scholar
  • 6 Bolton H, Graham SJL, Van der Aa N. et al. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nat Commun 2016; 7: 11165
    CrossrefPubMedSearch in Google Scholar
  • 7 Starostik MR, Sosina OA, McCoy RC. Single-cell analysis of human embryos reveals diverse patterns of aneuploidy and mosaicism. Genome Res 2020; 30 (06) 814-825
    CrossrefPubMedSearch in Google Scholar
  • 8 Sybert VP, Pagon RA, Donlan M, Bradley CM. Pigmentary abnormalities and mosaicism for chromosomal aberration: association with clinical features similar to hypomelanosis of Ito. J Pediatr 1990; 116 (04) 581-586
    CrossrefPubMedSearch in Google Scholar
  • 9 Wei HJ, Chiang HS, Lin WM, Wen JY. Pregnancy after preimplantation genetic diagnosis by fluorescence in situ hybridization using 18-, X-, and Y-chromosome probes in an infertile male with mosaic trisomy 18. J Assist Reprod Genet 2000; 17 (04) 229-231
    CrossrefPubMedSearch in Google Scholar
  • 10 Giannatou E, Leze H, Katana A. et al. Unilateral microtia in an infant with trisomy 18 mosaicism. Genet Couns 2009; 20 (02) 181-187
    PubMedSearch in Google Scholar
  • 11 Perrin A, Douet-Guilbert N, Le Bris MJ. et al. Increased aneuploidy rates in spermatozoa of a male carrier of a trisomy 18 mosaicism. Int J Androl 2009; 32 (03) 231-234
    CrossrefPubMedSearch in Google Scholar
  • 12 Fernandez KS, Baum R, Fung B. et al. Chemoresistant hepatoblastoma in a patient with mosaic trisomy 18 treated with orthotopic liver transplantation. Pediatr Blood Cancer 2011; 56 (03) 498-500
    CrossrefPubMedSearch in Google Scholar
  • 13 Pereira EM, Marion R, Ramesh KH, Kim JS, Ewart M, Ricafort R. Hepatoblastoma in a mosaic trisomy 18 patient. J Pediatr Hematol Oncol 2012; 34 (04) e145-e148
    CrossrefPubMedSearch in Google Scholar
  • 14 Banka S, Metcalfe K, Clayton-Smith J. Trisomy 18 mosaicism: report of two cases. World J Pediatr 2013; 9 (02) 179-181
    CrossrefPubMedSearch in Google Scholar
  • 15 Fitas AL, Paiva M, Cordeiro AI, Nunes L, Cordeiro-Ferreira G. Mosaic trisomy 18 in a five-month-old infant. Case Rep Pediatr 2013; 2013: 929861
    PubMedSearch in Google Scholar
  • 16 Bussmann N, Cunningham K, Green A, Ryan CA. Phenotypic extremes in liveborn monozygotic twins with mosaic Edwards syndrome. BMJ Case Rep 2015; 2015: bcr2015211587
    CrossrefPubMedSearch in Google Scholar
  • 17 Ahmad N, Wheeler K, Stewart H, Campbell C. Hepatoblastoma in a mosaic trisomy 18 child with hemihypertrophy. BMJ Case Rep 2016; 2016: bcr2015211380
    CrossrefPubMedSearch in Google Scholar
  • 18 Motta S, Sala D, Sala A. et al. Hodgkin lymphoma in a patient with mosaic trisomy 18: first clinical observation. Am J Med Genet A 2016; 170 (03) 777-780
    CrossrefPubMedSearch in Google Scholar
  • 19 Cammarata-Scalisi F, Lacruz-Rengel MAA, Araque D. et al. [Mosaic trisomy 18. Series of cases]. Arch Argent Pediatr 2017; 115 (03) e183-e186
    PubMedSearch in Google Scholar
  • 20 Inoue T, Nakamura A, Fuke T. et al. Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects. Clin Epigenetics 2017; 9: 52
    CrossrefPubMedSearch in Google Scholar
  • 21 Ganmore I, Smooha G, Izraeli S. Constitutional aneuploidy and cancer predisposition. Hum Mol Genet 2009; 18 (R1): R84-R93
    CrossrefPubMedSearch in Google Scholar
  • 22 Sheltzer JM, Torres EM, Dunham MJ, Amon A. Transcriptional consequences of aneuploidy. Proc Natl Acad Sci U S A 2012; 109 (31) 12644-12649
    CrossrefPubMedSearch in Google Scholar
  • 23 Gordon DJ, Resio B, Pellman D. Causes and consequences of aneuploidy in cancer. Nat Rev Genet 2012; 13 (03) 189-203
    CrossrefPubMedSearch in Google Scholar
  • 24 Giam M, Rancati G. Aneuploidy and chromosomal instability in cancer: a jackpot to chaos. Cell Div 2015; 10 (01) 3
    CrossrefPubMedSearch in Google Scholar
  • 25 Cereda A, Carey JC. The trisomy 18 syndrome. Orphanet J Rare Dis 2012; 7: 81
    CrossrefPubMedSearch in Google Scholar
  • 26 Kosho T, Kuniba H, Tanikawa Y, Hashimoto Y, Sakurai H. Natural history and parental experience of children with trisomy 18 based on a questionnaire given to a Japanese trisomy 18 parental support group. Am J Med Genet A 2013; 161A (07) 1531-1542
    CrossrefPubMedSearch in Google Scholar
  • 27 Boghossian NS, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Mortality and morbidity of VLBW infants with trisomy 13 or trisomy 18. Pediatrics 2014; 133 (02) 226-235
    CrossrefPubMedSearch in Google Scholar
  • 28 Acharya K, Leuthner S, Clark R, Nghiem-Rao TH, Spitzer A, Lagatta J. Major anomalies and birth-weight influence NICU interventions and mortality in infants with trisomy 13 or 18. J Perinatol 2017; 37 (04) 420-426
    CrossrefPubMedSearch in Google Scholar
  • 29 Koide K, Slonim DK, Johnson KL, Tantravahi U, Cowan JM, Bianchi DW. Transcriptomic analysis of cell-free fetal RNA suggests a specific molecular phenotype in trisomy 18. Hum Genet 2011; 129 (03) 295-305
    CrossrefPubMedSearch in Google Scholar
  • 30 El-Hattab AW, Adesina AM, Jones J, Scaglia F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab 2015; 116 (1-2): 4-12
    CrossrefPubMedSearch in Google Scholar
  • 31 Güler S, Gürkan H, Demir S. Is there an association between NC_012920.1: m.8277T> C mitochondrial variation the mt-NC7 locus, and migraine with aura?. Hippokratia 2020; 24 (02) 59-65
    PubMedSearch in Google Scholar
  • 32 Poole OV, Pizzamiglio C, Murphy D. et al; SYNaPS Study Group; Queen Square Genomics. Mitochondrial DNA analysis from exome sequencing data improves the diagnostic yield in neurological diseases. Ann Neurol 2021; 89 (06) 1240-1247
    CrossrefPubMedSearch in Google Scholar
  • 33 Li BU, Lefevre F, Chelimsky GG. et al; North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47 (03) 379-393
    CrossrefPubMedSearch in Google Scholar
  • 34 Kovacic K, Sood M, Venkatesan T. Cyclic vomiting syndrome in children and adults: what is new in 2018?. Curr Gastroenterol Rep 2018; 20 (10) 46
    CrossrefPubMedSearch in Google Scholar
  • 35 Daughtry BL, Chavez SL. Chromosomal instability in mammalian pre-implantation embryos: potential causes, detection methods, and clinical consequences. Cell Tissue Res 2016; 363 (01) 201-225
    CrossrefPubMedSearch in Google Scholar