CHROMOSOMAL DISEASES IN THE HUMAN PATHOLOGY
(review)
DOI:
https://doi.org/10.11603/ijmmr.2413-6077.2020.1.11501Keywords:
Down syndrome, Klinefelter syndrome, Turner syndrome, double aneuploidyAbstract
Background. Chromosomal diseases are the cause of 45-50 % of multiple birth defects. Basic research on mutations is performed using genomic technologies to identify a correlation between genotype and phenotype in aneuploidies and to understand its pathogenesis.
Objective. The aim of the research is to study the etiology, pathogenesis of symptoms and diagnostics for patients with Down, Klinefelter, Turner syndromes and double aneuploidies by 21 and sex chromosomes.
Methods. A literature review by the keywords “Down syndrome”, “Klinefelter syndrome”, “Turner syndrome”, “double aneuploidy” for the period of 2000-2020 was carried out.
Results. Down, Klinefelter and Turner syndromes are the most common aneuploidy among viable newborns. Frequency of meiotic non-disjunction events causing these aneuploidies increases with the age of a woman. Identified genes are responsible for pathogenesis of symptoms in trisomy 21, Turner and Klinefelter syndromes. Diagnostics of chromosomal diseases includes prenatal screening programs and postnatal testing.
Conclusions. Cytogenetic variants of Down syndrome are simple complete trisomy 21, translocation form and mosaicism. Trisomy 21 is associated with advanced maternal age. Phenotypic manifestations of Down syndrome are associated with the locus 21q22. The maternal and parental nondisjunction of X-chromosomes in meiosis causes Klinefelter and Turner syndromes. These chromosomal diseases are variants of intersexualism with intermediate chromosomal sex. Down-Klinefelter and Down-Turner syndromes are double aneuploidies. Patients have a Down syndrome phenotype at birth, and signs of Klinefelter and Turner syndromes occur during puberty. Diagnosis of aneuploidy is based on the cytogenetic investigation (karyotyping), DNA analysis, ultrasonography and biochemical markers of chromosomal pathology.
References
Bihunyak TV Current views on the causes and phenotypic manifestations of Down syndrome. The achievements of Clinical and Experimental medicine. 2008;1(8):7-11.
Protsyuk OV, Lynchak OV, Pokanevich TM Prevalence of chromosomal abnormalities among live births and stillbirths in Ukraine. Obstetrics. Gynecology. Genetics. 2017;3:37-41.
Kazemi M, Salehi M, Kheirollahi M Down Syndrome: Current Status, Challenges and Future Perspectives. Int J Mol Cell Med Summer. 2016; Vol 5 No 3:125-33.
Mathew AK, Amaladas AS, Ahmed A, Hameed S. Clinical Presentation of Down’s syndrome: A case report. The journal of medical research. 2017;3(3):107-9.
doi: 10.31254/jmr.2017.3304
Shankar RK, Backeljauw PF. Current best practice in the management of Turner syndrome. Therapeutic Advances in Endocrinology and Metabolism. 2018;9(1): 33-40.
doi: 10.1177/2042018817746291
Souza MP, Santos SM, Lima MM, Machado JM, Melo MM, Oliveira EH, Guerreiro JF. Chromosomal analyses in genetic counseling of patients with developmental and congenital abnormalities from Belém, Pará State, Brazil: a retrospective study of 17 years.
doi: 10.5123/S2176-6223201901597
Bihunyak TV Hereditary syndromes of intersexualism with an intermediate chromosomal sex. The achievements of Clinical and Experimental medicine. 2008;2(9):9-14.
Chebel Z, Krayem S, Nassif Y, et al. When Edwards meets Klinefelter: a new case of double Aneuploidy. J Pediatr Neonatal Care. 2019;9(2):65-6.
Pinti E, Lengyel A, Fekete G, et al. What should we consider in the case of combined Down- and 47,XY,+i(X)(q10) Klinefelter syndromes? The unique case of a male newborn and review of the literature. BMC Pediatrics. 2020;20:17.
doi: 10.1186/s12887-019-1905-9
Lan RY, Chou CT, Wang PH, Chen RC, Hsiao CH. Trisomy 21 screening based on first and second trimester in a Taiwanese population. Taiwanese Journal of Obstetrics and Gynecology. 2018 Aug 1;57(4):551-4.
doi: 10.1016/j.tjog.2018.06.014
Dooley KJ. Congenital Heart Disease and Down Syndrome In: Rubin IL, Merrick J, Greydanus DE, et al., editors. Health Care for People with Intellectual and Developmental Disabilities across the Lifespan: Springer. 2016:1301-10.
doi: 10.1007/978-3-319-18096-0_105
English C, Hammersley AL, Jackson A, Stenhouse S, Cross IE. Recurrent trisomy 21 resulting from gonadal mosaicism. Journal of Medical Genetics. 2001.
Coppedè F. Risk factors for Down syndrome. Archives of toxicology. 2016 Dec;90(12):2917-29.
doi: 10.1007/s00204-016-1843-3
PLAIASU V. Down syndrome–genetics and cardiogenetics. Maedica. 2017 Sep;12(3):208-13.
Gumus E. Two Rare Variants of Down Syndrome: Down-Turner Syndrome and Down Syndrome with Translocation (13; 14): A Case Report. Iranian Journal of Public Health. 2019 Nov;48(11):2079-82.
doi: 10.18502/ijph.v48i11.3529
Zaki MS, Kamel AA, El-Ruby M. Double aneuploidy in three Egyptian patients: Down-Turner and Down-Klinefelter syndromes. Genetic counseling. 2005 Jan 1;16(4):393-402.
Belling K, Russo F, Jensen AB, Dalgaard MD, Westergaard D, Rajpert-De Meyts E, Skakkebæk NE, Juul A, Brunak S. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity. Human Molecular Genetics. 2017 Apr 1;26(7):1219-29.
doi: 10.1093/hmg/ddx014
Gnetetskaya VA, Kurtser MA, Malmberg OL. Early diagnosis of fetal chromosomal pathology using the OSCAR program. Obstetrics and Gynecology. 2010;1:24-8.
Shargorodska EB. A retrospective evaluation of the condition of newborns with congenital heart defects. Lviv Medical Journal Acta Medica Leopoliensia. 2018;24(3):52-7.
doi: 10.25040/aml2018.03.052
Marder L, Tulloh R, Pascall E. Cardiac problems in Down syndrome. Paediatrics and Child Health. 2015 Jan 1;25(1):29.
doi: 10.1016/j.paed.2014.07.011
Jacobs EG, Leung MP, Karlberg J. Distribution of symptomatic congenital heart disease in Hong Kong. Pediatric cardiology. 2000 Mar 1;21(2):148-57.
doi: 10.1007/s002469910025
Kim MA, Lee YS, Yee NH, Choi JS, Choi JY, Seo K. Prevalence of congenital heart defects associated with Down syndrome in Korea. Journal of Korean Medical Science. 2014 Nov 1;29(11):1544-9.
doi: 10.3346/jkms.2014.29.11.1544
de Rubens Figueroa J, del Pozzo Magaña B, Pablos Hach JL, Calderón Jiménez C, Castrejón Urbina R. Heart malformations in children with Down syndrome. Revista Española de Cardiología (English Edition). 2003 Sep 1;56(9):894-9.
doi: 10.1016/s0300-8932(03)76978-4
Vida VL, Barnoya J, Larrazabal LA, Gaitan G, de Maria Garcia F, Castañeda AR. Congenital cardiac disease in children with Down’s syndrome in Guatemala. Cardiology in the Young. 2005 Jun;15(3):286-90.
doi: 10.1017/s1047951105000582
Elmagrpy Z, Rayani A, Shah A, et al. Down syndrome and congenital heart disease: why the regional difference as observed in the Libyan experience? Cardiovasc J Afr. 2011;22:306-9.
doi: 10.5830/cvja-2010-072
Barlow GM, Chen XN, Shi ZY, Lyons GE, Kurnit DM, Celle L, Spinner NB, Zackai E, Pettenati MJ, Van Riper AJ, Vekemans MJ. Down syndrome congenital heart disease: a narrowed region and a candidate gene. Genetics in Medicine. 2001 Mar;3(2):91-101.
doi: 10.1097/00125817-200103000-00002
Calkoen EE, Hazekamp MG, Blom NA, Elders BB, Gittenberger-de Groot AC, Haak MC, Bartelings MM, Roest AA, Jongbloed MR. Atrioventricular septal defect: From embryonic development to long-term follow-up. International journal of cardiology. 2016 Jan 1;202:784-95.
doi: 10.1016/j.ijcard.2015.09.081
Ackerman C, Locke AE, Feingold E, Reshey B, Espana K, Thusberg J, Mooney S, Bean LJ, Dooley KJ, Cua CL, Reeves RH. An excess of deleterious variants in VEGF-A pathway genes in Down-syndrome-associated atrioventricular septal defects. The American Journal of Human Genetics. 2012 Oct 5;91(4):646-59.
doi: 10.1016/j.ajhg.2012.08.017
Mateos MK, Barbaric D, Byatt SA, Sutton R, Marshall GM. Down syndrome and leukemia: insights into leukemogenesis and translational targets. Translational pediatrics. 2015 Apr;4(2):76-92.
doi: 10.3978/j.issn.22244336.2015.03.03
Sobey CG, Judkins CP, Sundararajan V, Phan TG, Drummond GR, Srikanth VK. Risk of major cardiovascular events in people with Down syndrome. PloS one. 2015 Sep 30;10(9):e0137093.
doi: 10.1371/journal.pone.0137093
Matthews-Brzozowska T, Cudziło D, Walasz J, Kawala B. Rehabilitation of the orofacial complex by means of a stimulating plate in children with Down syndrome. Adv Clin Exp Med. 2015 Mar 1;24(2):301-5.
doi: 10.17219/acem/40451
Sixou JL, Vernusset N, Daigneau A, Watine D, Marin L. Orofacial therapy in infants with Down syndrome. Journal of Dentofacial Anomalies and Orthodontics. 2017;20(1):108.
doi: 10.1051/odfen/2016038
Radoi VE, Bohiltea CL, Bohiltea RE, Albu DN. Cell free fetal DNA testing in maternal blood of Romanian pregnant women. Iranian journal of reproductive medicine. 2015 Oct;13(10):623-6.
Smith-Bindman R, Miglioretti DL, Sentilhes L, Salomon LJ, Vayssière C, Norton ME, Wapner RJ. Cell-free DNA analysis for noninvasive examination of trisomy. New England Journal of Medicine. 2015 Dec 24;373(26):2581-2.
doi: 10.1056/nejmc1509344
Meck JM, Dugan EK, Matyakhina L, Aviram A, Trunca C, Pineda-Alvarez D, Aradhya S, Klein RT, Cherry AM. Noninvasive prenatal screening for aneuploidy: positive predictive values based on cytogenetic findings. American journal of obstetrics and gynecology. 2015 Aug 1;213(2):214 e1-214 e5.
doi: 10.1016/j.ajog.2015.04.001
Taylor-Phillips S, Freeman K, Geppert J, Agbebiyi A, Uthman OA, Madan J, Clarke A, Quenby S, Clarke A. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ open. 2016 Jan 1;6(1).
doi: 10.1136/bmjopen-2015-010002
Fedorova NI, Tetruashvili NK, Demura TA et al. Importance of embryonic cells isolated from the cervical canal in early non-invasive prenatal diagnosis. Obstetrics and Gynecology 2010;1:28-31.
Linglart A, Cabrol S, Berlier P, Stuckens C, Wagner KD, De Kerdanet M, Limoni C, Carel JC, Chaussain JL. Growth hormone treatment before the age of 4 years prevents short stature in young girls with Turner syndrome. European journal of endocrinology. 2011 Jun 1;164(6):891-7.
doi: 10.1530/eje-10-1048
Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. European journal of endocrinology. 2017 Sep 1;177(3):G1-70.
doi: 10.1530/eje-17-0430
Knauer-Fischer S, Besikoglu B, Inta I, Kneppo C, Vogt PH, Bettendorf M. Analyses of gonadoblastoma Y (GBY)-locus and of Y centromere in Turner syndrome patients. Experimental and Clinical Endocrinology & Diabetes. 2015 Jan;123(01):61-5.
doi: 10.1055/s-0034-1387734
Lunding SA, Aksglæde L, Anderson RA, Main KM, Juul A, Hagen CP, Pedersen AT. AMH as predictor of premature ovarian insufficiency: a longitudinal study of 120 Turner syndrome patients. The Journal of Clinical Endocrinology & Metabolism. 2015 Jul 1;100(7):E1030-8.
doi: 10.1210/jc.2015-1621
Zaiem F, Alahdab F, Al Nofal A, Murad MH, Javed A. Oral versus transdermal estrogen in turner syndrome: a systematic review and meta-analysis. Endocrine Practice. 2017 Apr;23(4):408-21.
doi: 10.4158/ep161622.or
Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. The Lancet. 2004 Jul 17;364(9430):273-83.
doi: 10.1016/S0140-6736(04)16678-6
Kondo T, Kuroda S, Usui K, et al. A case of a rare variant of Klinefelter syndrome, 47,XY,i(X)(q10). Andrologia. 2018;17:e13024.
doi: 10.1111/and.13024
Dürrbaum M, Storchova Z. Effects of aneuploidyon gene expression: implications for cancer. FEBSJ. 2016; 283,791-802.
doi: 10.1111/febs.13591
Seminog OO, Seminog AB, Yeates D, Goldacre MJ. Associations between Klinefelter’s syndrome and autoimmune diseases: English national record linkage studies. Autoimmunity. 2015 Feb 17;48(2): 125-8.
doi: 10.3109/ 08916934.2014.968918
Samango-Sprouse CA, Sadeghin T, Mitchell FL, Dixon T, Stapleton E, Kingery M, Gropman AL. Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47, XXY syndrome at 36 and 72 months of age. American Journal of Medical Genetics Part A. 2013 Mar;161(3): 501-8.
doi: 10.1002/ajmg.a.35769
Bozdogan ST, Bisgin A. A rare double aneuploidy case (Down–Klinefelter). Journal of pediatric genetics. 2017 Dec;6(4):241-3.
doi: 10.1055/s-0037-1604098
Bozdogan ST, Bisgin A. A rare double aneuploidy case (Down–Klinefelter). Journal of pediatric genetics. 2017 Dec;6(4):241-3.
doi: 10.1055/s-0037-1604098
Shen Z, Zou CC, Shang SQ, Jiang KW. Down-Klinefelter syndrome (48, XXY,+ 21) in a child with congenital heart disease: case report and literature review. Internal Medicine. 2012;51(11):1371-4.
doi: 10.2169/internalmedicine.51.7097
Kovaleva NV, Mutton DE. Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes. American Journal of Medical Genetics Part A. 2005 Apr 1;134(1):24-32.
doi: 10.1002/ajmg.a.30306
Jeanty C, Turner C. Prenatal diagnosis of double aneuploidy, 48, XXY,+ 21, and review of the literature. Journal of Ultrasound in Medicine. 2009 May;28(5):673-81.
doi: 10.7863/jum.2009.28.5.673
Akgul M, Ozkinay F, Ercal D, Cogulu O, Dogan O, Altay B, Tavmergen E, Gunduz C, Ozkinay C. Cytogenetic abnormalities in 179 cases with male infertility in Western Region of Turkey: report and review. Journal of assisted reproduction and genetics. 2009 Mar 1;26(2-3):119-22.
doi: 10.1007/s10815-009-9296-8
Manassero-Morales G, Alvarez-Manassero D, Merino-Luna A. Down-Turner syndrome: A case with double monoclonal chromosomal abnormality. Case reports in pediatrics. 2016 Jan 1;2016.
doi: 10.1155/2016/8760504
Downloads
Published
How to Cite
Issue
Section
License
Authors who sent their manuscript to International Journal of Medicine and Medical Research agree to the following terms:
1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License CC-BY-NC that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
2. Authors able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
