Top

BMC Pediatrics

Published in:

Open Access 01-12-2020 | Chromosomal Abnormality | Case report

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

Authors: Eva Pinti, Anna Lengyel, Gyorgy Fekete, Iren Haltrich

Published in: BMC Pediatrics | Issue 1/2020

Abstract

Background

Double aneuploidies - especially in combination with structural aberrations - are extremely rare among liveborns. The most frequent association is that of Down (DS) and Klinefelter syndromes (KS). We present the case of a male newborn with a unique 47,XY,+ 21[80%]/48,XY,+i(X)(q10),+ 21[20%] karyotype, hypothesize about his future phenotype, discuss the aspects of management and review the literature.

Case presentation

The additional association of isochromosome Xq (i(X)(q10)) could be the result of a threefold non-disjunction event. 47,XY,+i(X)(q10) KS is not common and its symptoms differ from the classical KS phenotype. In combined DS and i(X)(q10) KS, the anticipatory phenotype is not simply the sum of the individual syndromic characteristics. This genotype is associated with higher risk for several diseases and certain conditions with more pronounced appearance: emotional and behavioral disorders; poorer mental and physical quality of life; lower muscle mass/tone/strength; connective tissue weakness; muscle hypotonia and feeding difficulties; osteopenia/−porosis with earlier beginning and faster progression; different types of congenital heart diseases; more common occurrence of hypertension; increased susceptibility to infections and female predominant autoimmune diseases; higher risk for hematological malignancies and testicular tumors.

Conclusions

In multiple aneuploidies, the alterations have the potential to weaken or enhance each other, or they may not have modifying effects at all. Prenatal ultrasound signs are not obligatory symptoms of numerous chromosomal anomalies (specifically those involving supernumerary sex chromosomes), therefore combined prenatal screening has pertinence in uncomplicated pregnancies as well.

Kovaleva NV, Mutton DE. Epidemiology of double aneuploidies involving chromosome 21 and the sex chromosomes. Am J Med Genet A. 2005;134A(01):24–32. https://doi.org/10.1002/ajmg.a.30306.CrossRefPubMed

Bozdogan ST, Bisgin A. A rare double aneuploidy case (Down–Klinefelter). J Pediatr Genet. 2017;6:241–3. https://doi.org/10.1055/s-0037-1604098.CrossRefPubMedPubMedCentral

Reddy UM, Page GP, Saade GR. The role of DNA microarrays in the evaluation of fetal death. Prenat Diagn. 2012;32(4):371–5. https://doi.org/10.1002/pd.3825.CrossRefPubMed

Shivakumar S, Venkat RP, Susan M. Double and multiple chromosomal aneuploidies in spontaneous abortions: a single institutional experience. J Hum Reprod Sci. 2014;7(4):262–8. https://doi.org/10.4103/0974-1208.147494.CrossRef

Illiopoulos D, Poultsides G, Peristeri V, Kouri G, Andreou A, Voyiatzis N. Double trisomy (48,XXY,+21) in monozygotic twins: case report and review of the literature. Ann Genet. 2004;47:95–8. https://doi.org/10.1016/j.anngen.2003.08.025.CrossRef

Lejeune J. Autosomal disorders. Pediatrics. 1963;32:326–37.PubMed

Tüttelmann F, Gromoll J. Novel genetic aspects of Kliefelter’s syndrome. Mol Hum Reprod. 2010;16(6):386–95. https://doi.org/10.1093/molehr/gaq019.CrossRefPubMed

Erickson JD. Down syndrome, paternal age, maternal age and birth order. Ann Hum Genet. 1978;41(3):289–98.CrossRef

Coppedé F. Risk factors for Down syndrome. Arch Toxicol. 2016;90(12):2917–29. https://doi.org/10.1007/s00204-016-1843-3.CrossRefPubMed

10.

Cheng L, Zhang DY, Eble JN. Molecular genetic pathology. New York: Humana Press; 2008. p. 45. https://doi.org/10.1007/978-1-59745-405-6_2.CrossRef

11.

Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364:273–83. https://doi.org/10.1016/S0140-6736(04)16678-6.CrossRefPubMed

12.

Kondo T, Kuroda S, Usui K, Mori K, Asai T, Takeshima T, et al. A case of a rare variant of Klinefelter syndrome, 47,XY,i(X)(q10). Andrologia. 2018;17:e13024. https://doi.org/10.1111/and.13024.CrossRef

13.

Lejeune J, Gautier M, Turpin R. Étude des chromosomes somatiques de neuf enfants mongoliens. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences (Paris). 1959;248:1721–1722. [Article in French].

14.

Patterson D. Molecular genetic analysis of Down syndrome. Hum Genet. 2009;126(1):195–214. https://doi.org/10.1007/s00439-009-0696-8.CrossRefPubMed

15.

Hasle H, Friedman JM, Olsen JH, Rasmussen SA. Low risk of solid tumors in persons with Down syndrome. Genet Med. 2016;18(11):1151–7. https://doi.org/10.1038/gim.2016.23.CrossRefPubMed

16.

Forés-Martos J, Cervera-Vidal R, Chirivella E, Ramos-Jarero A, Climent J. A genomic approach to study Down syndrome and cancer inverse comorbidity: untangling the chromosome 21. Front Physiol. 2015;4(6):10. https://doi.org/10.3389/fphys.2015.00010.CrossRef

17.

Sheltzer JM, Ko JH, Replogle JM, Habibe Burgos NC, Chung ES, Meehl CM, et al. Single-chromosome gains commonly function as tumor suppressors. Cancer Cell. 2016;31(2):240–55. https://doi.org/10.1016/j.ccell.2016.12.004.CrossRef

18.

Mateos MK, Barbaric D, Byatt S-A, Sutton R, Marshall GM. Down syndrome and leukemia: insights into leukemogenesis and translational targets. Transl Pediatr. 2015;4(2):76–92. https://doi.org/10.3978/j.issn.2224-4336.2015.03.03.CrossRefPubMedPubMedCentral

19.

Jacobs PA, Strong JA. Case of human intersexuality having possible XXY sex-determining mechanism. Nature. 1959;183:302–3.CrossRef

20.

Frühmesser A, Kotzot D. Chromosomal variants in Klinefelter syndrome. Sex Dev. 2011;5:109–23. https://doi.org/10.1159/000327324.CrossRefPubMed

21.

Bearelly P, Oates R. Recent advances in managing and understanding Klinefelter syndrome. F1000Research. 2019. https://doi.org/10.12688/f1000research F1000 Faculty Rev-112.

22.

Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Skakkebæk A. Klinefelter syndrome: integrating genetics, neuropsychology, and endocrinology. Endocr Rev. 2018;39(4):389–423. https://doi.org/10.1210/er.2017-00212.CrossRefPubMed

23.

Skakkebæk A, Nielsen MM, Trolle C, Vang S, Hornshøj H, Hedegaard J, et al. DNA hypermethylation and differential gene expression associated with Klinefelter syndrome. Sci Rep. 2018;8(1):13740. https://doi.org/10.1038/s41598-018-31780-0.CrossRefPubMedPubMedCentral

24.

Migeon BR. Choosing the active X: the human version of X inactivation. Trends Genet. 2017;33(12):899–909. https://doi.org/10.1016/j.tig.2017.09.005.CrossRefPubMed

25.

Seminog OO, Seminog AB, Yeates D, Goldacre MJ. Associations between Klinefelter’s syndrome and autoimmune diseases: English national record linkage studies. Autoimmunity. 2015;48(2):125–8. https://doi.org/10.3109/08916934.2014.968918.CrossRefPubMed

26.

Disteche M, Berletch JB. X-chromosome inactivation and escape. J Genet. 2015;94(4):591–9.CrossRef

27.

Bakalov VK, Gutin L, Cheng CM, Zhou J, Sheth P, Shah K, et al. Autoimmune disorders in women with Turner syndrome and women with karyotypically normal primary ovarian insufficiency. J Autoimmun. 2012;38(4):315–21. https://doi.org/10.1016/j.jaut.2012.01.015.CrossRefPubMedPubMedCentral

28.

Ford CE, Jones KW, Miller OJ, et al. The chromosomes in a patient showing both mongolism and the Klinefelter syndrome. Lancet. 1959;1(7075):709–10.CrossRef

29.

Jeanty C, Turner C. Prenatal diagnosis of double aneuploidy, 48,XXY,+21, and review of the literature. J Ultrasound Med. 2009;28:673–81. https://doi.org/10.7863/jum.2009.28.5.673.CrossRefPubMed

30.

Wright SW, Day RW, Moiser HD, Koons A, Mueller H. Klinefelter's syndrome. Down's syndrome (mongolism), and twinning in the same sibship. J Pediatr. 1963;62:217–24.CrossRef

31.

Rodrigues MA, Morgade LF, Dias LFA, Moreira RV, Maia PD, Sales AFH, et al. Down-Klinefelter syndrome (48,XXY,+21) in a neonate associated with congenital heart disease. Genet Mol Res. 2017;16(3). https://doi.org/10.4238/gmr16039780.

Title: 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
Authors: Eva Pinti
Anna Lengyel
Gyorgy Fekete
Iren Haltrich
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Chromosomal Abnormality
Trisomy 21
Klinefelter Syndrome
Leukemia
Published in: BMC Pediatrics / Issue 1/2020
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-019-1905-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Case presentation

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Case presentation

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2020

Water, sanitation and hygiene practices associated with improved height-for-age, weight-for-height and weight-for-age z-scores among under-five children in Nepal

Enteroviral and herpes simplex virus central nervous system infections in infants < 90 days old: a Paediatric Investigators’ Collaborative Network on Infections in Canada (PICNIC) study

Type of facility influences lengths of stay of children presenting to high volume emergency departments

Experiences and training needs of healthcare providers involved in the care of Ghanaian adolescents living with HIV: an interventional study

Determinants of healthcare seeking for childhood illnesses among caregivers of under-five children in urban slums in Malawi: a population-based cross-sectional study

C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay: a quality improvement initiative