Abstract
Sex chromosome multisomies (SCMs) are genomic conditions with variable phenotypes that range from undetectable to requiring extensive clinical intervention. Currently, many individuals with SCMs are diagnosed in adolescence or adulthood based on physical symptoms related to pubertal development and infertility. Given the expansion of genetic testing in routine clinical practice, the diagnosing clinician is increasingly a primary care or family medicine provider. This study aims to help providers better understand the patient experience of receiving a diagnosis. We conducted a survey of individuals (n = 55) with SCMs using closed and open-ended questions. Open-response questions were qualitatively analyzed and are reported here with the descriptive results of the closed-ended questions. Most participants were diagnosed with 47,XXY (n = 51; 85.0%), identified as White race/ethnicity (n = 46; 88.5%), and were college graduates or higher (n = 29; 54.7%). Many participants reported dissatisfaction with the delivery of the diagnosis, expressing that it was rushed and their provider lacked detailed information about the condition. Participants were frustrated by the general lack of availability of high-quality informational resources from both medical and other sources at the time of diagnosis. Some participants also described the social and psychological impact of the diagnosis and how it was delivered. To the best of our knowledge, this is the largest survey of individuals diagnosed with SCMs, which is notable considering their prevalence and low diagnostic rate. Our findings provide patient-informed insight on how to improve the delivery of SCM diagnoses, especially delivery in a primary care setting, including the provision of up-to-date information and proactive referral to specialty care and counseling services.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Abdullah S, Jarvik LF, Kato T, Johnston WC, Lanzkron J (1969) Extra Y chromosome and its psychiatric implications. Arch Gen Psychiatry 21(4):497–501. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/490092
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins, O., Genetics, C. O., & Society for Maternal-Fetal Medicine, 2020 American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins, O., Genetics, C. O., & Society for Maternal-Fetal Medicine. (2020). Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol 136(4):e48-e69.https://doi.org/10.1097/AOG.0000000000004084
Association for X and Y Chromosome Variations. About X and Y Variations. https://genetic.org/variations/
Berglund A, Viuff MH, Skakkebæk A, Chang S, Stochholm K, Gravholt CH (2019) Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47, XXX and 47, XYY syndrome: a nationwide cohort study. Orphanet J Rare Dis 14(1):16. https://doi.org/10.1186/s13023-018-0976-2
Broadstock M, Michie S, Marteau T (2000) Psychological consequences of predictive genetic testing: a systematic review. Eur J Hum Genet 8(10):731–738. https://doi.org/10.1038/sj.ejhg.5200532
Close S, Talboy A, Fennoy I (2017) Complexities of care in Klinefelter syndrome: an APRN perspective. Pediatr Endocrinol Rev 14(Suppl 2):462–471. https://doi.org/10.17458/per.vol14.2017.ctf.complexitiescareklinefelter
Davis S, Howell S, Wilson R, Tanda T, Ross J, Zeitler P, Tartaglia N (2016) Advances in the Interdisciplinary Care of Children with Klinefelter Syndrome. Adv Pediatr 63(1):15–46. https://doi.org/10.1016/j.yapd.2016.04.020
de Vries ALC, Roehle R, Marshall L, Frisén L, van de Grift TC, Kreukels BPC, Bouvattier C, Köhler B, Thyen U, Nordenström A, Rapp M, Cohen-Kettenisdsd-LIFE PTG (2019) Mental Health of a Large Group of Adults With Disorders of Sex Development in Six European Countries. Psychosom Med 81(7):629–640. https://doi.org/10.1097/PSY.0000000000000718
Herlihy AS, Gillam L (2011) Thinking outside the square: considering gender in Klinefelter syndrome and 47 XXY. Int J Androl 34(5 Pt 2):e348–e349. https://doi.org/10.1111/j.1365-2605.2010.01132.x
Herlihy AS, McLachlan RI, Gillam L, Cock ML, Collins V, Halliday JL (2011) The psychosocial impact of Klinefelter syndrome and factors influencing quality of life. Genet Med 13(7):632–642. https://doi.org/10.1097/GIM.0b013e3182136d19
Heshka JT, Palleschi C, Howley H, Wilson B, Wells PS (2008) A systematic review of perceived risks, psychological and behavioral impacts of genetic testing. Genet Med 10(1):19–32. https://doi.org/10.1097/GIM.0b013e31815f524f
Hoskovec JM, Bennett RL, Carey ME, DaVanzo JE, Dougherty M, Hahn SE, LeRoy BS, O’Neal S, Richardson JG, Wicklund CA (2018) Projecting the supply and demand for certified genetic counselors: a workforce study. J Genet Couns 27(1):16–20. https://doi.org/10.1007/s10897-017-0158-8
Howard-Bath A, Poulton A, Halliday J, Hui L (2018) Population-based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non-invasive prenatal testing. Prenat Diagn 38(13):1062–1068. https://doi.org/10.1002/pd.5363
Hull LE, Gold NB, Armstrong KA (2020) Revisiting the Roles of Primary Care Clinicians in Genetic Medicine. JAMA 324(16):1607–1608. https://doi.org/10.1001/jama.2020.18745
Jaramillo C, Nyquist C, Riggan KA, Egginton J, Phelan S, Allyse M (2019) Delivering the diagnosis of sex chromosome aneuploidy: experiences and preferences of parents and individuals. Clin Pediatr (phila) 58(3):336–342. https://doi.org/10.1177/0009922818817310
May CP, Dein A, Ford J (2020) New insights into the formation and duration of flashbulb memories: evidence from medical diagnosis memories. Appl Cogn Psychol 34(5):1154–1165. https://onlinelibrary.wiley.com/doi/abs/10.1002/acp.3704
McAllister M, Davies L, Payne K, Nicholls S, Donnai D, MacLeod R (2007) The emotional effects of genetic diseases: implications for clinical genetics. Am J Med Genet A 143A(22):2651–2661. https://doi.org/10.1002/ajmg.a.32013
McRobert CJ, Hill JC, Smale T, Hay EM, van der Windt DA (2018) A multi-modal recruitment strategy using social media and internet-mediated methods to recruit a multidisciplinary, international sample of clinicians to an online research study. PLoS ONE 13(7):e0200184. https://doi.org/10.1371/journal.pone.0200184
Melnyk J, Derencsenyi A, Vanasek F, Rucci AJ, Thompson H (1969) XYY Survey in an Institution for Sex Offenders and the Mentally III. Nature 224(5217):369–370. https://www.nature.com/articles/224369a0
Meredith S (2020) Understanding Klinefelter syndrome. http://understandingklinefeltersyndrome.org/
Milunsky A, Milunsky JM (2015) Genetic disorders and the fetus: diagnosis, prevention, and treatment. John Wiley & Sons
O’Brien BC, Harris IB, Beckman TJ, Reed DA, Cook DA (2014) Standards for reporting qualitative research: a synthesis of recommendations. Acad Med 89(9):1245–1251. https://journals.lww.com/academicmedicine/fulltext/2014/09000/standards_for_reporting_qualitative_research__a.21.aspx
Richardson JP, Riggan KA, Allyse M (2021) The expert in the room: parental advocacy for children with sex chromosome aneuploidies. J Dev Behav Pediatr 42(3):213–219. https://doi.org/10.1097/DBP.0000000000000885
Riggan KA, Close S, Allyse MA (2020) Family experiences and attitudes about receiving the diagnosis of sex chromosome aneuploidy in a child. Am J Med Genet C Semin Med Genet 184(2):404–413. https://doi.org/10.1002/ajmg.c.31781
Riggan KA, Gross B, Close S, Weinberg A, Allyse MA (2021) Prenatal genetic diagnosis of a sex chromosome aneuploidy: parent experiences. J Genet Couns. https://doi.org/10.1002/jgc4.1407
Saldana J (2016) The Coding Manual for Qualitative Researchers. SAGE.
Samango-Sprouse C, Kırkızlar E, Hall MP, Lawson P, Demko Z, Zneimer SM, Curnow KJ, Gross S, Gropman A (2016) Incidence of X and Y chromosomal aneuploidy in a large child bearing population. PLoS ONE 11(8):e0161045. https://doi.org/10.1371/journal.pone.0161045
Schoubben E, Decaestecker K, Quaegebeur K, Danneels L, Mortier G, Cornette L (2011) Tetrasomy and pentasomy of the X chromosome. Eur J Pediatr 170(10):1325–1327. https://doi.org/10.1007/s00431-011-1491-9
Skotko B (2005) Mothers of children with Down syndrome reflect on their postnatal support. Pediatrics 115(1):64–77. https://doi.org/10.1542/peds.2004-0928
Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L (2010) A review of trisomy X (47, XXX). Orphanet J Rare Dis 5:8. https://doi.org/10.1186/1750-1172-5-8
Tartaglia N, Ayari N, Howell S, D’Epagnier C, Zeitler P (2011) 48, XXYY, 48, XXXY and 49, XXXXY syndromes: not just variants of Klinefelter syndrome. Acta Paediatr 100(6):851–860. https://doi.org/10.1111/j.1651-2227.2011.02235.x
Thompson T, Davis S, Takamatsu S, Howell S, Tartaglia N (2022) Exploring academic and character strengths in students with sex chromosome aneuploidies. J Posit School Psychol 6(1):12–24. https://journalppw.com/index.php/jpsp/article/download/133/127
Thorn P (2009) Understanding infertility: psychological and social considerations from a counselling perspective. Int J Fertil Steril 3(2):48–51. http://www.ijfs.ir/article_40686.html
Tsuboi T (1970) Crimino-biologic study of patients with the XYY syndrome and Klinefelter’s syndrome. Humangenetik 10(1):68–84. https://link.springer.com/article/10.1007/bf00297642
Turriff A, Macnamara E, Levy HP, Biesecker B (2017) The impact of living with klinefelter syndrome: a qualitative exploration of adolescents and adults. J Genet Couns 26(4):728–737. https://doi.org/10.1007/s10897-016-0041-z
van Rijn S (2019) A review of neurocognitive functioning and risk for psychopathology in sex chromosome trisomy (47, XXY, 47, XXX, 47, XYY). Curr Opin Psychiatry 32(2):79–84. https://doi.org/10.1097/YCO.0000000000000471
Visootsak J, Ayari N, Howell S, Lazarus J, Tartaglia N (2013) Timing of diagnosis of 47, XXY and 48, XXYY: a survey of parent experiences. Am J Med Genet A 161A(2):268–272. https://doi.org/10.1002/ajmg.a.35709
Acknowledgements
We thank the respondents for sharing their experiences with us. This publication was supported by grant number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This study was supported by the Mayo Clinic Center for Individualized Medicine Bioethics Program. MA is additionally supported by K01 HG009542.
Funding
This work was supported by Mayo Clinic’s Center for Individualized Medicine.
Author information
Authors and Affiliations
Contributions
Megan A. Allyse and Sharron Close conceptualized and designed the study. Data collection was conducted by Kirsten A. Riggan. Data analysis was performed by Jordan P. Richardson and Nivedita Ahlawat. Jordan P. Richardson drafted the manuscript and all authors provided feedback on earlier versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethics approval
This study was reviewed and determined to be minimal risk by Mayo Clinic’s Institutional Review Board. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 its later amendments. This article does not contain any studies with animal subjects performed by the any of the authors.
Consent to participate
Implied informed consent was obtained for all individuals who voluntarily completed the online survey.
Consent for publication
Participants consented to have their anonymous results used for research.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Richardson, J.P., Ahlawat, N., Riggan, K.A. et al. Experiences of individuals receiving a sex chromosome multisomy diagnosis. J Community Genet 13, 619–628 (2022). https://doi.org/10.1007/s12687-022-00604-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12687-022-00604-0