Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Pediatrics
Published in: BMC Pediatrics 1/2024

Open Access 01-12-2024 | Klinefelter Syndrome | Research

Evidence-based recommendations for delivering the diagnosis of X & Y chromosome multisomies in children, adolescents, and young adults: an integrative review

Authors: Kirsten A. Riggan, Kelly E. Ormond, Megan A. Allyse, Sharron Close

Published in: BMC Pediatrics | Issue 1/2024

Login to get access

Abstract

Background

The diagnosis of supernumerary X & Y chromosome variations has increased following the implementation of genetic testing in pediatric practice. Empirical evidence suggests that the delivery of the diagnosis has a lasting impact on how affected individuals and their parents perceive and adapt to the diagnosis. The purpose of this review is to synthesize the literature to obtain useful recommendations for delivering a pediatric diagnosis of a sex chromosome multisomy (SCM) based upon a growing body of quantitative and qualitative literature on patient experiences.

Methods

We conducted an integrative literature review using PubMed, Web of Science and CINAHL employing keywords “genetic diagnosis delivery,” “genetic diagnosis disclosure,” “sex chromosome aneuploidy,” “Klinefelter syndrome” or “”47, XXY,” “Jacob syndrome” or “47, XYY,” “Trisomy X,” “Triple X” or “47, XXX,” and “48 XXYY from January 1, 2000, to October 31, 2023.

Results

Literature supports that patients and parents value the provision of up-to-date information and connection with supportive resources. Discussion of next steps of care, including relevant referrals, prevents perceptions of provider abandonment and commitment to ongoing support. Proactively addressing special concerns such as disclosing the diagnosis to their child, family, and community is also beneficial. Tables are provided for useful information resources, medical specialties that may be required to support patients, and common misconceptions that interfere with accurate information about the diagnosis.

Conclusion

Patient experiences suggest there should be heightened attention to diagnosis delivery, in reference to the broader ethical and social impacts of a SCM diagnosis. We present recommendations for optimal disclosure of a SCM diagnosis in early and late childhood, adolescence, and young adulthood.
Appendix
Available only for authorised users
Literature
1.
Milunsky A, Huang X, Amos JA, Herskowitz J, Farrer LA, Wyandt HE. 46, XY/47, XYY male with the fragile X syndrome: cytogenetic and molecular studies. Am J Med Genet. 1993;45(5):589–93.PubMedCrossRef
2.
Berglund A, Stochholm K, Gravholt CH. The epidemiology of sex chromosome abnormalities. Am J Med Genet C Semin Med Genet. 2020;184(2):202–15.PubMedCrossRef
3.
Ricciardi G, Cammisa L, Bove R, Picchiotti G, Spaziani M, Isidori AM, et al. Clinical, cognitive and neurodevelopmental profile in tetrasomies and pentasomies: a systematic review. Children (Basel). 2022;9(11):1719.PubMed
4.
Tartaglia N, Ayari N, Howell S, D’Epagnier C, Zeitler P. 48, XXYY, 48, XXXY and 49, XXXXY syndromes: not just variants of Klinefelter syndrome. Acta Paediatr. 2011;100(6):851–60.PubMedPubMedCentralCrossRef
5.
Otter M, Crins PML, Campforts BCM, Stumpel C, van Amelsvoort T, Vingerhoets C. Social functioning and emotion recognition in adults with triple X syndrome. BJPsych Open. 2021;7(2):e51.PubMedPubMedCentralCrossRef
6.
Tartaglia N, Howell S, Davis S, Kowal K, Tanda T, Brown M, et al. Early neurodevelopmental and medical profile in children with sex chromosome trisomies: background for the prospective eXtraordinarY babies study to identify early risk factors and targets for intervention. Am J Med Genet C Semin Med Genet. 2020;184(2):428–43.PubMedPubMedCentralCrossRef
7.
Wigby K, D’Epagnier C, Howell S, Reicks A, Wilson R, Cordeiro L, Tartaglia N. Expanding the phenotype of triple X syndrome: a comparison of prenatal versus postnatal diagnosis. Am J Med Genet A. 2016;170(11):2870–81.PubMedPubMedCentralCrossRef
8.
Hong DS, Reiss AL. Cognitive and neurological aspects of sex chromosome aneuploidies. Lancet Neurol. 2014;13(3):306–18.PubMedCrossRef
9.
Bardsley MZ, Kowal K, Levy C, Gosek A, Ayari N, Tartaglia N, et al. 47, XYY syndrome: clinical phenotype and timing of ascertainment. J Pediatr. 2013;163(4):1085–94.PubMedPubMedCentralCrossRef
10.
Cordeiro L, Tartaglia N, Roeltgen D, Ross J. Social deficits in male children and adolescents with sex chromosome aneuploidy: a comparison of XXY, XYY, and XXYY syndromes. Res Dev Disabil. 2012;33(4):1254–63.PubMedPubMedCentralCrossRef
11.
12.
Leggett V, Jacobs P, Nation K, Scerif G, Bishop DV. Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review. Dev Med Child Neurol. 2010;52(2):119–29.PubMedPubMedCentralCrossRef
13.
Bearelly P, Oates R. Recent advances in managing and understanding Klinefelter syndrome. F1000Res. 2019;8:369–80.CrossRef
14.
Close S, Talboy A, Fennoy I. Complexities of care in klinefelter syndrome: an APRN Perspective. Pediatr Endocrinol Rev. 2017;14(Suppl 2):462–71.PubMed
15.
Davis S, Howell S, Wilson R, Tanda T, Ross J, Zeitler P, Tartaglia N. Advances in the interdisciplinary care of children with klinefelter syndrome. Adv Pediatr. 2016;63(1):15–46.PubMedPubMedCentralCrossRef
16.
Urbanus E, van Rijn S, Swaab H. A review of neurocognitive functioning of children with sex chromosome trisomies: identifying targets for early intervention. Clin Genet. 2020;97(1):156–67.PubMedCrossRef
17.
Saul RA, Trotter T, Sease K, Tarini B. Survey of family history taking and genetic testing in pediatric practice. J Community Genet. 2017;8(2):109–15.PubMedPubMedCentralCrossRef
18.
Rinke ML, Mikat-Stevens N, Saul R, Driscoll A, Healy J, Tarini BA. Genetic services and attitudes in primary care pediatrics. Am J Med Genet A. 2014;164A(2):449–55.PubMedCrossRef
19.
Berglund A, Viuff MH, Skakkebaek A, Chang S, Stochholm K, Gravholt CH. 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. 2019;14(1):16.PubMedPubMedCentralCrossRef
20.
Tremblay I, Grondin S, Laberge AM, Cousineau D, Carmant L, Rowan A, Janvier A. Diagnostic and therapeutic misconception: parental expectations and perspectives regarding genetic testing for developmental disorders. J Autism Dev Disord. 2019;49(1):363–75.PubMedCrossRef
21.
22.
Loughry L, Pynaker C, White M, Halliday J, Hui L. State-wide increase in prenatal diagnosis of klinefelter syndrome on amniocentesis and chorionic villus sampling: Impact of non-invasive prenatal testing for sex chromosome conditions. Prenat Diagn. 2023;43(2):156–61.PubMedCrossRef
23.
Howard-Bath A, Poulton A, Halliday J, Hui L. Population-based trends in the prenatal diagnosis of sex chromosome aneuploidy before and after non-invasive prenatal testing. Prenat Diagn. 2018;38(13):1062–8.PubMedCrossRef
24.
May C, Dein A, Ford J. New insights into the formation and duration of flashbulb memories: Evidence from medical disgnosis memories. Appl Cogn Psychol. 2020;34:1154–65.CrossRef
25.
Riggan KA, Close S, Allyse MA. Family experiences and attitudes about receiving the diagnosis of sex chromosome aneuploidy in a child. Am J Med Genet C Semin Med Genet. 2020;184(2):404–13.PubMedPubMedCentralCrossRef
26.
Jaramillo C, Nyquist C, Riggan KA, Egginton J, Phelan S, Allyse M. Delivering the diagnosis of sex chromosome aneuploidy: experiences and preferences of parents and individuals. Clin Pediatr (Phila). 2019;58(3):336–42.PubMedCrossRef
27.
Riggan KA, Gross B, Close S, Steinberg A, Allyse MA. “Knowledge is power”: parent views on the benefits of early diagnosis and awareness of sex chromosome multisomy among pediatric professionals. J Dev Behav Pediatr. 2023;44(2):e119–25.PubMedCrossRef
28.
Visootsak J, Ayari N, Howell S, Lazarus J, Tartaglia N. Timing of diagnosis of 47, XXY and 48, XXYY: a survey of parent experiences. Am J Med Genet A. 2013;161A(2):268–72.PubMedCrossRef
29.
ME B. Integrative reviews for the development of concepts. In: Rodgers B, Knafl K, editors. Concept Development in Nursing. 2nd ed. Philadelphia, PA: WB Saunders Co.; 1993.
30.
Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546–53.PubMedCrossRef
31.
McGowan J, Straus S, Moher D, Langlois EV, O’Brien KK, Horsley T, et al. Reporting scoping reviews-PRISMA ScR extension. J Clin Epidemiol. 2020;123:177–9.PubMedCrossRef
32.
Tricco AC, Lillie E, Zarin W, O’Brien KK, Colquhoun H, Levac D, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467–73.PubMedCrossRef
33.
Close S, Sadler L, Grey M. In the dark: challenges of caring for sons with klinefelter syndrome. J Pediatr Nurs. 2016;31(1):11–20.PubMedCrossRef
34.
Richardson JP, Ahlawat N, Riggan KA, Close S, Allyse MA. Experiences of individuals receiving a sex chromosome multisomy diagnosis. J Community Genet. 2022;13(6):619–28.PubMedPubMedCentralCrossRef
35.
Richardson JP, Riggan KA, Allyse M. The expert in the room: parental advocacy for children with sex chromosome aneuploidies. J Dev Behav Pediatr. 2021;42(3):213–9.PubMedCrossRef
36.
Riggan KA, Gross B, Close S, Weinberg A, Allyse MA. Prenatal genetic diagnosis of a sex chromosome aneuploidy: parent experiences. J Genet Couns. 2021;30(5):1407–17.PubMedCrossRef
37.
Bourke E, Snow P, Herlihy A, Amor D, Metcalfe S. A qualitative exploration of mothers’ and fathers’ experiences of having a child with Klinefelter syndrome and the process of reaching this diagnosis. Eur J Hum Genet. 2014;22(1):18–24.PubMedCrossRef
38.
Dennis A, Howell S, Cordeiro L, Tartaglia N. “How should I tell my child?” Disclosing the diagnosis of sex chromosome aneuploidies. J Genet Couns. 2015;24(1):88–103.PubMedCrossRef
39.
Aliberti L, Gagliardi I, Bigoni S, Lupo S, Caracciolo S, Ferlini A, et al. Communicating the diagnosis of Klinefelter syndrome to children and adolescents: when, how, and who? J Community Genet. 2022;13(3):271–80.PubMedPubMedCentralCrossRef
40.
Gratton NC, Myring J, Middlemiss P, Shears D, Wellesley D, Wynn S, et al. Children with sex chromosome trisomies: parental disclosure of genetic status. Eur J Hum Genet. 2016;24(5):638–44.PubMedCrossRef
41.
Tremblay I, Van Vliet G, Gonthier M, Janvier A. Partnering with parents to disclose Klinefelter syndrome to their child. Acta Paediatr. 2016;105(5):456–61.PubMedCrossRef
42.
Linden MG, Bender BG, Robinson A. Genetic counseling for sex chromosome abnormalities. Am J Med Genet. 2002;110(1):3–10.PubMedCrossRef
43.
Tartaglia N, Howell S, Wilson R, Janusz J, Boada R, Martin S, et al. The eXtraordinarY kids clinic: an interdisciplinary model of care for children and adolescents with sex chromosome aneuploidy. J Multidiscip Healthc. 2015;8:323–34.PubMedPubMedCentralCrossRef
44.
Ashtiani S, Makela N, Carrion P, Austin J. Parents’ experiences of receiving their child’s genetic diagnosis: a qualitative study to inform clinical genetics practice. Am J Med Genet A. 2014;164A(6):1496–502.PubMedPubMedCentralCrossRef
45.
Harrison ME, Walling A. What do we know about giving bad news? A review Clin Pediatr (Phila). 2010;49(7):619–26.PubMedCrossRef
46.
47.
VandeKieft GK. Breaking bad news. Am Fam Physician. 2001;64(12):1975–8.PubMed
48.
Bourke E, Herlihy A, Snow P, Metcalfe S, Amor D. Klinefelter syndrome - a general practice perspective. Aust Fam Physician. 2014;43(1):38–41.PubMed
49.
Davis SM, Soares K, Howell S, Cree-Green M, Buyers E, Johnson J, Tartaglia NR. Diminished ovarian reserve in girls and adolescents with trisomy X syndrome. Reprod Sci. 2020;27(11):1985–91.PubMedCrossRef
50.
Davis SM, Bloy L, Roberts TPL, Kowal K, Alston A, Tahsin A, et al. Testicular function in boys with 47, XYY and relationship to phenotype. Am J Med Genet C Semin Med Genet. 2020;184(2):371–85.PubMedPubMedCentralCrossRef
51.
Davis SM, Rogol AD, Ross JL. Testis development and fertility potential in boys with klinefelter syndrome. Endocrinol Metab Clin North Am. 2015;44(4):843–65.PubMedPubMedCentralCrossRef
52.
Stochholm K, Bojesen A, Jensen AS, Juul S, Gravholt CH. Criminality in men with Klinefelter’s syndrome and XYY syndrome: a cohort study. BMJ Open. 2012;2(1):e000650.PubMedPubMedCentralCrossRef
53.
Ridder LO, Berglund A, Stochholm K, Chang S, Gravholt CH. Morbidity, mortality, and socioeconomics in Klinefelter syndrome and 47, XYY syndrome: a comparative review. Endocr Connect. 2023;12(5):e230024.PubMedPubMedCentralCrossRef
54.
Szigety KM, Crowley TB, Gaiser KB, Chen EY, Priestley JRC, Williams LS, et al. Clinical effectiveness of telemedicine-based pediatric genetics care. Pediatrics. 2022;150(1):e2021054520.PubMedCrossRef
55.
56.
57.
Thompson T, Davis S, Takamatsu S, Howell S, Tartaglia N. Exploring academic and character strengths in students with sex chromosome aneuploidies. J Positive School Psychol. 2022;6:12–24.CrossRef
58.
Thompson T, Davis S, Janusz J, Frith E, Pyle L, Howell S, et al. Supporting students with sex chromosome aneuploidies in educational settings: results of a nationwide survey. J Sch Psychol. 2022;93:28–40.PubMedPubMedCentralCrossRef
59.
60.
Thompson T, Stinnett N, Tartaglia N, Davis S, Janusz J. “I Wish the school had a better understanding of the diagnosis”: parent perspectives on educational needs of students with sex chromosome aneuploidies. J Res Spec Educ Needs. 2022;22(2):175–87.PubMedPubMedCentralCrossRef
61.
Zganjar A, Nangia A, Sokol R, Ryabets A, Samplaski MK. Fertility in adolescents with klinefelter syndrome: a survey of current clinical practice. J Clin Endocrinol Metab. 2020;105(4):e1883–91.CrossRef
62.
Dwyer AA, Heritier V, Llahana S, Edelman L, Papadakis GE, Vaucher L, et al. Navigating disrupted puberty: development and evaluation of a mobile-health transition passport for klinefelter syndrome. Front Endocrinol (Lausanne). 2022;13:909830.PubMedCrossRef
63.
64.
Turriff A, Macnamara E, Levy HP, Biesecker B. The impact of living with klinefelter syndrome: a qualitative exploration of adolescents and adults. J Genet Couns. 2017;26(4):728–37.PubMedCrossRef
65.
66.
McConkie-Rosell A, Spiridigliozzi GA, Melvin E, Dawson DV, Lachiewicz AM. Living with genetic risk: effect on adolescent self-concept. Am J Med Genet C Semin Med Genet. 2008;148C(1):56–69.PubMedPubMedCentralCrossRef
67.
Ahlawat N, Elliott K, Ormond KE, Allyse MA, Riggan KA. Healthcare and support experiences of adolescents and young adults diagnosed with 47, XXY, 47, XXX, and 48 XXYY. J Community Genet. 2023;15(1):75–83.PubMedPubMedCentralCrossRef
68.
Committee on Bioethics and The American College of Medical Genetics and Genomics Social EaLIC. Ethical and ploicy issues in genetic testing and screening of chidren. Pediatrics. 2013;131:620–2.
69.
70.
Turriff A, Levy HP, Biesecker B. Factors associated with adaptation to Klinefelter syndrome: the experience of adolescents and adults. Patient Educ Couns. 2015;98(1):90–5.PubMedCrossRef
71.
Bester J, Sabatello M, van Karnebeek CDM, Lantos JD. Please test my child for a cancer gene, but don’t tell her. Pediatrics. 2018;141(4):e20172238.PubMedCrossRef
72.
Cole CM, Kodish E. Minors’ right to know and therapeutic privilege. Virtual Mentor. 2013;15(8):638–44.PubMed
73.
Hudson N, Spriggs M, Gillam L. Telling the truth to young children: ethical reasons for information disclosure in paediatrics. J Paediatr Child Health. 2019;55(1):13–7.PubMedCrossRef
74.
Metcalfe A, Coad J, Plumridge GM, Gill P, Farndon P. Family communication between children and their parents about inherited genetic conditions: a meta-synthesis of the research. Eur J Hum Genet. 2008;16(10):1193–200.PubMedCrossRef
75.
Metcalfe A, Plumridge G, Coad J, Shanks A, Gill P. Parents’ and children’s communication about genetic risk: a qualitative study, learning from families’ experiences. Eur J Hum Genet. 2011;19(6):640–6.PubMedPubMedCentralCrossRef
Metadata
Title
Evidence-based recommendations for delivering the diagnosis of X & Y chromosome multisomies in children, adolescents, and young adults: an integrative review
Authors
Kirsten A. Riggan
Kelly E. Ormond
Megan A. Allyse
Sharron Close
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2024
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-024-04723-0

Other articles of this Issue 1/2024

BMC Pediatrics 1/2024 Go to the issue

Research

Evaluation of differential renal function in children – a comparative study between magnetic resonance urography and dynamic renal scintigraphy

Research

Effect of non-pharmacological interventions on pain in preterm infants in the neonatal intensive care unit: a network meta-analysis of randomized controlled trials

Case Report

Detection of a novel gross deletion in the UNC13D gene ends the diagnostic odyssey for a family with familial hemophagocytic lymphohistiocytosis 3

Research

Undernutrition in young children with congenital heart disease undergoing cardiac surgery in a low-income environment

Case Report

A case report of peroneal muscle atrophy type 2A2 with central nervous system involvement as initial presentation

Research

Effectiveness of Back care education Programme among school children: a systematic review of randomized controlled trials