How do genetic tests answer questions about neurodevelopmental differences? A sociological take.
Journal
Developmental medicine and child neurology
ISSN: 1469-8749
Titre abrégé: Dev Med Child Neurol
Pays: England
ID NLM: 0006761
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
11
03
2022
received:
17
09
2021
accepted:
13
06
2022
pubmed:
14
8
2022
medline:
3
11
2022
entrez:
13
8
2022
Statut:
ppublish
Résumé
When it comes to neurodevelopmental differences, a genetic test result can provide compelling answers. However, it is not always clear what the relevant question is. If we want to understand the impact of a genetic diagnosis such as NGLY1 deficiency or the fragile X, trisomy X, or 22q11.2 deletion syndromes on people with neurodevelopmental differences, we must be mindful about what exactly a genetic test is supposed to tell us, where and for whom it matters, and which avenues for action it opens or forecloses. These are all moving targets. Specifically, I discuss the shifting ways a genetic test result can answer the following questions. What is this person's diagnosis? What symptoms and developmental differences are they likely to experience? What is the best way to approach their development, treatment, and care? Will they have a life worth living? When you unpack the sociological nuances of each question, the history behind them, and the uneven ways they are asked, the meanings of the answers change quite radically. I discuss the implications for social inequalities and urge experts and stakeholders to exercise agency when they interpret a genetic diagnosis. WHAT THIS PAPER ADDS: The questions a genetic test can answer depend on a range of social factors. Whether and how a genetic test result affects diagnosis, identity, prognosis, and treatment is a moving target. Genetics creates questions about a life worth living that it cannot answer alone. Stakeholders must choose the questions about neurodevelopmental differences that genetics should answer.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1462-1469Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 Mac Keith Press.
Références
Adams D. The Hitchhiker's Guide to the Galaxy. Harmony Books; 1980. 232 p.
Phillips KA, Deverka PA, Hooker GW, Douglas MP. Genetic Test Availability And Spending: Where Are We Now? Where Are We Going? Health Affairs. 2018 May 1;37(5):710-6.
Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies. The American Journal of Human Genetics. 2010 May 14;86(5):749-64.
Martin CL, Ledbetter DH. Chromosomal Microarray Testing for Children With Unexplained Neurodevelopmental Disorders. JAMA. 2017 Jun 27;317(24):2545-6.
Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. AMERICAN JOURNAL OF MEDICAL GENETICS PART A. 2006 Oct 1;140A(19):2063-74.
Clark MM, Stark Z, Farnaes L, Tan TY, White SM, Dimmock D, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. npj Genomic Med. 2018 Jul 9;3(1):1-10.
Srivastava S, Love-Nichols JA, Dies KA, Ledbetter DH, Martin CL, Chung WK, et al. Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genet Med. 2019 Nov;21(11):2413-21.
Blesson A, Cohen JS. Genetic Counseling in Neurodevelopmental Disorders. Cold Spring Harb Perspect Med. 2019 Sep 9;a036533.
Thevenon J, Duffourd Y, Masurel-Paulet A, Lefebvre M, Feillet F, Chehadeh-Djebbar SE, et al. Diagnostic odyssey in severe neurodevelopmental disorders: toward clinical whole-exome sequencing as a first-line diagnostic test. Clinical Genetics. 2016;89(6):700-7.
Finucane B, Challman TD, Martin CL, Ledbetter DH. Shift happens: family background influences clinical variability in genetic neurodevelopmental disorders. Genet Med. 2016 Apr;18(4):302-4.
Navon D. Mobilizing Mutations: Human Genetics in the Age of Patient Advocacy. Chicago and London: University of Chicago Press; 2019. 384 p.
Insel T. Transforming Diagnosis [Internet]. NIMH Director's Blog. 2013. Available from: http://www.nimh.nih.gov/about/director/2013/transforming-diagnosis.shtml
Ozonoff S. Editorial Perspective: Autism Spectrum Disorders in DSM-5 - An historical perspective and the need for change. Journal of Child Psychology and Psychiatry. 2012;53(10):1092-4.
Finucane B, Haas-Givler B, Simon EW. Genetics, mental retardation, and the forging of new alliances. Am J Med Genet. 2003 Feb;117C(1):66-72.
National Fragile X Foundation 25th Anniversary [Internet]. 2009 [cited 2012 Apr 19]. Available from: http://www.youtube.com/watch?v=KMMY8WYuIMY&feature=youtube_gdata_player
Mnookin S. One of a Kind. The New Yorker [Internet]. 2014 Jul 21 [cited 2014 Jul 20]; Available from: http://www.newyorker.com/reporting/2014/07/21/140721fa_fact_mnookin?currentPage=all
Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, et al. Practical Guidelines for Managing Patients with 22q11.2 Deletion Syndrome. Journal of Pediatrics. 2011 Aug;159(2):332-339.e1.
Ledbetter DH. Cytogenetic Technology -- Genotype and Phenotype. N Engl J Med. 2008 Oct 16;359(16):1728-30.
Navon D. “The Gene Didn't Get the Memo”: Realigning Disciplines and Remaking Illness in Genomic Medicine. Critical Inquiry. 2020 Jun 1;46(4):867-90.
Leggett V, Jacobs P, Nation K, Scerif G, Bishop DVM. Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: a systematic review. Dev Med Child Neurol. 2010 Feb;52(2):119-29.
MacMillan DL, Semmel MI, Gerber MM. The Social Context of Dunn Then and Now. J Spec Educ. 1994 Jan 1;27(4):466-80.
Klein-Tasman BP, Phillips KD, Lord CE, Mervis CB, Gallo F. Overlap with the Autism Spectrum in Young Children with Williams Syndrome. J Dev Behav Pediatr. 2009 Aug;30(4):289-99.
Navon D, Eyal G. Looping genomes: Diagnostic change and the genetic makeup of the autism population. AJS. 2016 Mar;121(5):1416-71.
Yu TW, Berry-Kravis E. Autism and Fragile X Syndrome. Semin Neurol. 2014 Jul;34(3):258-65.
Moreno-De-Luca A, Myers SM, Challman TD, Moreno-De-Luca D, Evans DW, Ledbetter DH. Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. The Lancet Neurology. 2013 Apr;12(4):406-14.
Brandler WM, Sebat J. From De Novo Mutations to Personalized Therapeutic Interventions in Autism. Annual Review of Medicine. 2015;66(1):487-507.
Sanchez-Roige S, Palmer AA. Emerging phenotyping strategies will advance our understanding of psychiatric genetics. Nature Neuroscience. 2020 Apr 1;23(4):475-80.
Gottesman II, Gould TD. The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions. AJP. 2003 Apr;160(4):636-45.
Insel TR, Cuthbert BN. Endophenotypes: Bridging Genomic Complexity and Disorder Heterogeneity. Biological Psychiatry. 2009 Dec 1;66(11):988-9.
Dobzhansky T. Evolution, Genetics and Man. First American Edition. New York: John Wiley and Sons; 1955. 398 p.
Unolt M, Versacci P, Anaclerio S, Lambiase C, Calcagni G, Trezzi M, et al. Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well-established knowledge to new frontiers. American Journal of Medical Genetics Part A. 2018;176(10):2087-98.
Bittles AH, Glasson EJ. Clinical, social, and ethical implications of changing life expectancy in Down syndrome. Developmental Medicine and Child Neurology. 2004 Apr;46(4):282-6.
Iyer AA, Saade D, Bharucha-Goebel D, Foley AR, Averion G ‘Mike,’ Paredes E, et al. Ethical challenges for a new generation of early-phase pediatric gene therapy trials. Genet Med. 2021 Jul 7;1-10.
Riggs E. R., Wain K E., Riethmaier D, Smith-Packard B, Faucett W A., Hoppman N, et al. Chromosomal microarray impacts clinical management. Clin Genet. 2014 Feb 1;85(2):147-53.
Tao VQ, Chan KYK, Chu YWY, Mok GTK, Tan TY, Yang W, et al. The Clinical Impact of Chromosomal Microarray on Paediatric Care in Hong Kong. PLOS ONE. 2014 Oct 15;9(10):e109629.
Committee on Bioethics. Ethical Issues With Genetic Testing in Pediatrics. Pediatrics. 2001 Jun 1;107(6):1451-5.
Bulaklak K, Gersbach CA. The once and future gene therapy. Nat Commun. 2020 Nov 16;11(1):5820.
Hildebrandt CC, Marron JM. Justice in CRISPR/Cas9 Research and Clinical Applications. AMA Journal of Ethics. 2018 Sep 1;20(9):826-33.
Visootsak J, Kidd SA, Anderson T, Bassell JL, Sherman SL, Berry-Kravis EM. Importance of a specialty clinic for individuals with fragile X syndrome. Am J Med Genet. 2016 Sep 1;170(12):3144-9.
AXYS. 47, XYY syndrome [Internet]. 2016. Available from: https://genetic.org/wp-content/uploads/2016/09/AXYS-XYY-Brochure-updated-12-10-16.pdf
Bardsley MZ, Kowal K, Levy C, Gosek A, Ayari N, Tartaglia N, et al. 47,XYY Syndrome: Clinical Phenotype and Timing of Ascertainment. The Journal of Pediatrics. 2013 Oct;163(4):1085-94.
Urbanus E, Swaab H, Tartaglia N, Boada R, van Rijn S. A cross-sectional study of early language abilities in children with sex chromosome trisomy (XXY, XXX, XYY) aged 1-6 years. Child Neuropsychology. 2022 Feb 17;28(2):171-96.
Gravholt CH, Tartaglia N, Disteche C. Sex chromosome aneuploidies in 2020-The state of care and research in the world. Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):197-201.
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 Jan;97(1):156-67.
Thompson T, Howell S, Davis S, Wilson R, Janusz J, Boada R, et al. Current survey of early childhood intervention services in infants and young children with sex chromosome aneuploidies. Am J Med Genet C Semin Med Genet. 2020 Jun;184(2):414-27.
Parens E, Asch A. Disability rights critique of prenatal genetic testing: reflections and recommendations. Ment Retard Dev Disabil Res Rev. 2003;9(1):40-7.
Dimmock D, Caylor S, Waldman B, Benson W, Ashburner C, Carmichael JL, et al. Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children's hospitals demonstrates improved clinical outcomes and reduced costs of care. Am J Hum Genet. 2021 Jun 4;108(7):1231-8 [cited 2021 Jun 28]; Available from: https://www.sciencedirect.com/science/article/pii/S0002929721001920
Gubbels CS, VanNoy GE, Madden JA, Copenheaver D, Yang S, Wojcik MH, et al. Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield. Genet Med. 2020 Apr;22(4):736-44.
Löwy I. Tangled Diagnoses: Prenatal Testing, Women, and Risk [Internet]. Chicago, IL: University of Chicago Press; 2018 [cited 2022 Jan 24]. 352 p. Available from: https://press.uchicago.edu/ucp/books/book/chicago/T/bo27949393.html
Ravitsky V, Roy M-C, Haidar H, Henneman L, Marshall J, Newson AJ, et al. The Emergence and Global Spread of Noninvasive Prenatal Testing. Annual Review of Genomics and Human Genetics. 2021;22(1):309-38.
Haidar H, Dupras C, Ravitsky V. Non-Invasive Prenatal Testing: Review of Ethical, Legal and Social Implications. 2016 Feb 26 [cited 2017 Feb 6]; Available from: https://papyrus.bib.umontreal.ca/xmlui/handle/1866/13176
Navon D, Thomas G. Screening Before We Know: Radical Uncertainties in Expanded Prenatal Genetics. OBM Genetics. 2021 Oct;5(4):1-1.
Pieters JJPM, Kooper AJA, van Kessel AG, Braat DDM, Smits APT. Incidental Prenatal Diagnosis of Sex Chromosome Aneuploidies: Health, Behavior, and Fertility. ISRN Obstet Gynecol. 2011;2011:807106.
Wigby K, D'Epagnier C, Howell S, Reicks A, Wilson R, Cordeiro L, et al. Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis. Am J Med Genet. 2016 Sep 1;n/a-n/a.
Bishop DVM, Brookman-Byrne A, Gratton N, Gray E, Holt G, Morgan L, et al. Language phenotypes in children with sex chromosome trisomies. Wellcome Open Res. 2018;3:143.
Werner-Lin A, Walser S, Barg FK, Bernhardt BA. “They Can't Find Anything Wrong with Him, Yet”: Mothers' experiences of parenting an infant with a prenatally diagnosed copy number variant (CNV). Am J Med Genet. 2016 Nov 1;n/a-n/a.
Lippman A. Prenatal Genetic Testing and Screening: Constructing Needs and Reinforcing Inequities. Am JL & Med. 1991;17:15-50.
Löwy I. Non-invasive prenatal testing: A diagnostic innovation shaped by commercial interests and the regulation conundrum. Social Science & Medicine. 2020 May 20;113064.
Shaffer BL, Caughey AB, Norton ME. Variation in the decision to terminate pregnancy in the setting of fetal aneuploidy. Prenatal Diagnosis. 2006;26(8):667-71.
Hamamy HA, Dahoun S. Parental decisions following the prenatal diagnosis of sex chromosome abnormalities. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2004 Sep 10;116(1):58-62.
Whose genomics? Nat Hum Behav. 2019 May;3(5):409-10.
Nelkin D, Lindee MS. The DNA Mystique: The Gene as a Cultural Icon. University of Michigan Press; 2004. 320 p.
Duster T. Backdoor to Eugenics. 2nd ed. New York and London: Routledge; 2003. 264 p.