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Genetic Health Care Before Conception

  • Martina C. CornelEmail author
  • Selina Goodman
  • Lidewij Henneman
Chapter
  • 21 Downloads

Abstract

Every child inherits two copies of their genes, one from each of their biological parents, and in this way genes are passed on to the next generation. Often people do not think about their genes, until they have a child born with a recessive condition. When they then ask the question: ‘Could we have known before that we are carrier of this disorder?’, the theoretical answer is ‘Yes’, since they would have been carriers throughout their lives. However, testing for carrier status often is done only after the birth of an affected infant, potentially followed by testing relatives. Medical issues related to genetic factors being passed on are preferably discussed before pregnancy, since the impact of inherited disorders to the lives of parents and their family may be enormous. For some couples, the risk for each child to have an inherited disease is 25%, 50% or, though rarely, even 100%. It is therefore important that time is available for providing information about a possible genetic risk to couples planning a pregnancy. This chapter will discuss (1) genetic health care in relation to preconception care (goal, autonomy, informed decision-making); (2) family history and patterns of inheritance, especially recessive conditions; and (3) techniques that are used in the genetic laboratories in 2019 (more or less targeted, from simple high-performance liquid chromatography (HPLC)/electrophoresis for HbP to expanded carrier screening using sequencing techniques or analyses as in whole exome sequencing (WES) for consanguineous couples).

Keywords

Genetics Genetic disorders Preconception carrier screening Expanded carrier screening Autosomal recessive Genetic counselling Family history Consanguinity 

References

  1. Abacan M, Alsubaie L, Barlow-Stewart K, Caanen B, Cordier C, Courtney E, et al. The global state of the genetic counseling profession. Eur J Hum Genet. 2019;27:183–97.  https://doi.org/10.1038/s41431-018-0252-x.CrossRefPubMedGoogle Scholar
  2. American College of Obstetricians and Gynecologists. Committee opinion no. 691: carrier screening for genetic conditions. Obstet Gynecol. 2017;129:597–9.  https://doi.org/10.1097/AOG.0000000000001952.CrossRefGoogle Scholar
  3. American College of Obstetricians and Gynecologists Committee on Genetics. ACOG Committee opinion no. 486: update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011;117:1028–31.  https://doi.org/10.1097/AOG.0b013e31821922c2.CrossRefGoogle Scholar
  4. Arribas-Ayllon MS, Sarangi S. Counselling uncertainty: genetics professionals’ accounts of (non)directiveness and trust/distrust. Health Risk Soc. 2014;16:171–84.  https://doi.org/10.1080/13698575.2014.884545.CrossRefGoogle Scholar
  5. Atrash H, Jack BW, Johnson K. Preconception care: a 2008 update. Curr Opin Obstet Gynecol. 2008;20:581–9.  https://doi.org/10.1097/GCO.0b013e328317a27c.CrossRefPubMedGoogle Scholar
  6. Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, et al. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med. 2011;3:65ra4.  https://doi.org/10.1126/scitranslmed.3001756.CrossRefPubMedPubMedCentralGoogle Scholar
  7. BenNagi J, Serhal P, SenGupta S, Doye K, Wells D. Preimplantation genetic diagnosis: an overview and recent advances. Obstetric Gynaecol. 2016;18:99–106.  https://doi.org/10.1111/tog.12264.CrossRefGoogle Scholar
  8. Bennett RL. The family medical history as a tool in preconception consultation. J Community Genet. 2012;3:175–83.  https://doi.org/10.1007/s12687-012-0107-z.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bishop M, Metcalfe S, Gaff C. The missing element: consanguinity as a component of genetic risk assessment. Genet Med. 2008;10:612–20.CrossRefGoogle Scholar
  10. Bittles A. Consanguinity and its relevance to clinical genetics. Clin Genet. 2001;60:89–98.  https://doi.org/10.1034/j.1399-0004.2001.600201.x.CrossRefPubMedGoogle Scholar
  11. Carrell DT, Jenkins TG, Emery BR, Hotaling JM, Aston KI. The role of reproductive genetics in modern andrology. In: Palermo G, Sills E, editors. Intracytoplasmic sperm injection. Cham: Springer; 2018. p. 23–38.CrossRefGoogle Scholar
  12. Chivers Seymour K, Addington-Hall J, Lucassen AM, Foster CL. What facilitates or impedes family communication following genetic testing for cancer risk? A systematic review and meta-synthesis of primary qualitative research. J Genet Couns. 2010;19:330–42.  https://doi.org/10.1007/s10897-010-9296-y.CrossRefPubMedGoogle Scholar
  13. Cousens NE, Gaff CL, Metcalfe SA, Delatycki MB. Carrier screening for beta-thalassaemia: a review of international practice. Eur J Hum Genet. 2010;18:1077–83.  https://doi.org/10.1038/ejhg.2010.90.CrossRefPubMedPubMedCentralGoogle Scholar
  14. de Souza DAS, Faucz FR, Pereira-Ferrari L, Sotomaior VS, Raskin S. Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: reproductive implications and genetic counseling. Andrology. 2018;6:127–35.CrossRefGoogle Scholar
  15. de Weerd S, van der Bij AK, Braspenning JC, Cikot RJ, Braat DD, Steegers EA. Psychological impact of preconception counseling: assessment of anxiety before and during pregnancy. Community Genet. 2001;4:129–33.  https://doi.org/10.1159/000051172.CrossRefPubMedGoogle Scholar
  16. de Wert G, Dondorp WJ, Knoppers BM. Preconception care and genetic risk: ethical issues. J Community Genet. 2012;3:221–8.  https://doi.org/10.1007/s12687-011-0074-9.CrossRefPubMedGoogle Scholar
  17. Deciphering Developmental Disorders Study. Prevalence and architecture of de novo mutations in developmental disorders. Nature. 2017;542:433–8.  https://doi.org/10.1038/nature21062.CrossRefGoogle Scholar
  18. Delatycki MB, Alkuraya F, Archibald A, Castellani C, Cornel M, Grody WW, Henneman L, Ioannides AS, Kirk E, Laing N, Lucassen A, Massie J, Schuurmans J, Thong MK, van Langen I, Zlotogora J. International perspectives on the implementation of reproductive carrier screening. Prenat Diagn. 2020;40(3):301–10.  https://doi.org/10.1002/pd.5611.CrossRefPubMedGoogle Scholar
  19. Delatycki MB, Burke J, Christie L, Collins F, Gabbett M, George P, et al. Human Genetics Society of Australasia position statement: population-based carrier screening for cystic fibrosis. Twin Res Hum Genet. 2014;17:578–83.  https://doi.org/10.1017/thg.2014.65.CrossRefPubMedGoogle Scholar
  20. Dheensa S, Lucassen A, Fenwick A. Limitations and pitfalls of using family letters to communicate genetic risk: a qualitative study with patients and healthcare professionals. J Genet Couns. 2018;27:689–701.  https://doi.org/10.1007/s10897-017-0164-x.CrossRefPubMedGoogle Scholar
  21. Doka KJ. How we die: stigmatized death and disenfranchised grief. In: Doka KJ, editor. Disenfranchised grief: new directions, challenges, and strategies for practice. Champaign, IL: Research Press; 2002. p. 323–36. ISBN-13: 978-0878224272.Google Scholar
  22. Edwards JG, Feldman G, Goldberg J, Gregg AR, Norton ME, Rose NC, et al. Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol. 2015;125:653–62.  https://doi.org/10.1097/AOG.0000000000000666.CrossRefPubMedGoogle Scholar
  23. Elwyn G, Gray J, Clarke A. Shared decision making and non-directiveness in genetic counselling. J Med Genet. 2000;37:135–8.  https://doi.org/10.1136/jmg.37.2.135.CrossRefPubMedPubMedCentralGoogle Scholar
  24. European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber L, Davies M, Anderson R, Bartlett J, Braat D, Cartwright B, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31:926–37.  https://doi.org/10.1093/humrep/dew027.CrossRefGoogle Scholar
  25. Flannigan R, Schlegel PN. Genetic diagnostics of male infertility in clinical practice. Best Pract Res Clin Obstet Gynaecol. 2017;44:26–37.  https://doi.org/10.1016/j.bpobgyn.2017.05.002.CrossRefPubMedGoogle Scholar
  26. Forrest LE, Curnow L, Delatycki MB, Skene L, Aitken M. Health first, genetics second: exploring families’ experiences of communicating genetic information. Eur J Hum Genet. 2008;16:1329–35.  https://doi.org/10.1038/ejhg.2008.104.CrossRefPubMedGoogle Scholar
  27. Girard SL, Bourassa CV, Lemieux Perreault LP, Legault MA, Barhdadi A, Ambalavanan A, et al. Paternal age explains a major portion of de novo germline mutation rate variability in healthy individuals. PLoS One. 2016;11:e0164212.  https://doi.org/10.1371/journal.pone.0164212.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Global Prevalence of Consanguinity. n.d. http://consang.net/index.php/Global_prevalence. Accessed 7 Sept 2019.
  29. Hamamy H. Consanguineous marriages: preconception consultation in primary health care settings. J Community Genet. 2012;3:185–92.  https://doi.org/10.1007/s12687-011-0072-y.CrossRefPubMedGoogle Scholar
  30. Henneman L, Borry P, Chokoshvili D, Cornel MC, van El CG, Forzano F, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet. 2016;24:e1–e12.  https://doi.org/10.1038/ejhg.2015.271.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Holtkamp KCA, Mathijssen IB, Lakeman P, van Maarle MC, Dondorp WJ, Henneman L, Cornel MC. Factors for successful implementation of population-based expanded carrier screening: learning from existing initiatives. Eur J Pub Health. 2017;27:372–7.  https://doi.org/10.1093/eurpub/ckw110.CrossRefGoogle Scholar
  32. Hyde KJ, Schust DJ. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med. 2015;5:a023119.  https://doi.org/10.1101/cshperspect.a023119.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ioannides AS. Preconception and prenatal genetic counselling. Best Pract Res Clin Obstet Gynaecol. 2017;42:2–10.  https://doi.org/10.1016/j.bpobgyn.2017.04.003.CrossRefPubMedGoogle Scholar
  34. Jack BW, Atrash H, Coonrod DV, Moos MK, O’Donnell J, Johnson K. The clinical content of preconception care: an overview and preparation of this supplement. Am J Obstet Gynecol. 2008;199(Suppl 2):S266–79.  https://doi.org/10.1016/j.ajog.2008.07.067.CrossRefPubMedGoogle Scholar
  35. Kaback MM. Screening and prevention in Tay-Sachs disease: origins, update, and impact. Adv Genet. 2001;44:253–65.  https://doi.org/10.1016/S0065-2660(01)44084-3.CrossRefPubMedGoogle Scholar
  36. Kessler S. Psychological aspects of genetic counseling. XI. Nondirectiveness revisited. Am J Med Genet. 1997;72:164–71.  https://doi.org/10.1002/(sici)1096-8628(19971017)72:2<164::aid-ajmg8>3.0.co;2-v.CrossRefPubMedGoogle Scholar
  37. Kingsmore S. Comprehensive carrier screening and molecular diagnostic testing for recessive childhood diseases. PLoS Curr. 2012:e4f9877ab8ffa9.  https://doi.org/10.1371/4f9877ab8ffa9.
  38. Kirk EP, Barlow-Stewart K, Selvanathan A, Josephi-Taylor S, Worgan L, Rajagopalan S, Cowley MJ, Gayevskiy V, Bittles A, Burnett L, Elakis G, Lo W, Buckley M, Colley A, Roscioli T. Beyond the panel: preconception screening in consanguineous couples using the TruSight one “clinical exome”. Genet Med. 2019;21:608–12.  https://doi.org/10.1038/s41436-018-0082-9.CrossRefPubMedGoogle Scholar
  39. Lazarin GA, Haque IS, Nazareth S, Iori K, Patterson AS, Jacobson JL, Marshall JR, Seltzer WK, Patrizio P, Evans EA, Srinivasan BS. An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals. Genet Med. 2013;15:178–86.  https://doi.org/10.1038/gim.2012.114.CrossRefPubMedGoogle Scholar
  40. Lewis C, Skirton H, Jones R. Reproductive empowerment: the main motivator and outcome of carrier testing. J Health Psychol. 2012;17:567–78.  https://doi.org/10.1177/1359105311417193.CrossRefPubMedGoogle Scholar
  41. Mathijssen IB, Henneman L, Van Eeten-Nijman JM, et al. Targeted carrier screening for four recessive disorders: high detection rate within a founder population. Eur J Med Genet. 2015;58:123–8.  https://doi.org/10.1016/j.ejmg.2015.01.004.CrossRefPubMedGoogle Scholar
  42. McAllister M, Davies L, Payne K, Nicholls S, Donnai D, MacLeod R. The emotional effects of genetic diseases: implications for clinical genetics. Am J Med Genet A. 2007;143A:2651–61.  https://doi.org/10.1002/ajmg.a.32013.CrossRefPubMedGoogle Scholar
  43. McClaren BJ, Metcalfe SA, Aitken M, Massie RJ, Ukoumunne OC, Amor DJ. Uptake of carrier testing in families after cystic fibrosis diagnosis through newborn screening. Eur J Hum Genet. 2010;18:1084–9.  https://doi.org/10.1038/ejhg.2010.78.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Mendes Á, Metcalfe A, Paneque M, Sousa L, Clarke AJ, Sequeiros J. Communication of information about genetic risks: putting families at the center. Fam Process. 2018;57:836–46.  https://doi.org/10.1111/famp.12306.CrossRefPubMedGoogle Scholar
  45. 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;16:1193–200.  https://doi.org/10.1038/ejhg.2008.84.CrossRefPubMedGoogle Scholar
  46. Milsom S, O’Sullivan S. Premature ovarian insufficiency. O&G Magazine. 2017;19(1). https://www.ogmagazine.org.au/19/1-19/premature-ovarian-insufficiency/. Accessed 1 May 2019.
  47. Oliveira LM, Seminara SB, Beranova M, Hayes FJ, Valkenburgh SB, Schipani E, Costa EM, Latronico AC, Crowley WF Jr, Vallejo M. The importance of autosomal genes in Kallmann syndrome: genotype-phenotype correlations and neuroendocrine characteristics. J Clin Endocrinol Metab. 2001;86:1532–8.  https://doi.org/10.1210/jcem.86.4.7420.CrossRefPubMedGoogle Scholar
  48. Oosterwal G. Multicultural counseling. In: Uhlmann WR, Schuette JL, Yashar B, editors. A guide to genetic counseling. Hoboken, NJ: John Wiley & Sons; 2009. p. 331–61. ISBN: 978-0-470-17965-9.Google Scholar
  49. Patch C, Middleton A. Genetic counselling in the era of genomic medicine. Br Med Bull. 2018;126:27–36.  https://doi.org/10.1093/bmb/ldy008.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Qin Y, Jiao X, Simpson JL, Chen ZJ. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 2015;21:787–808.  https://doi.org/10.1093/humupd/dmv036.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Riedijk S, Oudesluijs G, Tibben A. Psychosocial aspects of preconception consultation in primary care: lessons from our experience in clinical genetics. J Community Genet. 2012;3:213–9.  https://doi.org/10.1007/s12687-012-0095-z.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Ropers HH. On the future of genetic risk assessment. J Community Genet. 2012;3:229–36.  https://doi.org/10.1007/s12687-012-0092-2.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Sallevelt SCEH, de Koning B, Szklarczyk R, Paulussen ADC, de Die-Smulders CEM, Smeets HJM. A comprehensive strategy for exome-based preconception carrier screening. Genet Med. 2017;19:583–92.  https://doi.org/10.1038/gim.2016.153.CrossRefPubMedGoogle Scholar
  54. Salway S, Ali P, Ratcliffe G, Such E, Khan N, Kingston H, Quarrell O. Responding to the increased genetic risk associated with customary consanguineous marriage among minority ethnic populations: lessons from local innovations in England. J Community Genet. 2016;7:215–28.  https://doi.org/10.1007/s12687-016-0269-1.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Sankaranarayanan K. Ionizing radiation and genetic risks IX. Estimates of the frequencies of mendelian diseases and spontaneous mutation rates in human populations: a 1998 perspective. Mutat Res. 1998;411:129–78.  https://doi.org/10.1016/S1383-5742(98)00012-X.CrossRefPubMedGoogle Scholar
  56. Shaw A. Drivers of cousin marriage among British Pakistanis. Hum Hered. 2014;77:26–36.  https://doi.org/10.1159/000358011.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Sheridan E, Wright J, Small N, Corry PC, Oddie S, Whibley C, Petherick ES, Malik T, Pawson N, McKinney PA, Parslow RC. Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study. Lancet. 2013;382(9901):1350–9.  https://doi.org/10.1016/S0140-6736(13)61132-0.CrossRefPubMedGoogle Scholar
  58. Skirton H. More than an information service: are counselling skills needed by genetics professionals in the genomic era? Eur J Hum Genet. 2018;26:1239–40.  https://doi.org/10.1038/s41431-018-0133-3.CrossRefPubMedPubMedCentralGoogle Scholar
  59. Skirton H, Goldsmith L, Jackson L, Lewis C, Chitty L. Offering prenatal diagnostic tests: European guidelines for clinical practice. Eur J Hum Genet. 2014;22:580–6.  https://doi.org/10.1038/ejhg.2013.205.CrossRefPubMedGoogle Scholar
  60. Sobel S, Cowan CB. Ambiguous loss and disenfranchised grief: the impact of DNA predictive testing on the family as a system. Fam Process. 2003;42:47–57.  https://doi.org/10.1111/j.1545-5300.2003.00047.x.CrossRefPubMedGoogle Scholar
  61. Solomon BD, Jack BW, Feero WG. The clinical content of preconception care: genetics and genomics. Am J Obstet Gynecol. 2008;199:S340–4.  https://doi.org/10.1016/j.ajog.2008.09.870.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Teeuw ME, Hagelaar A, Ten Kate LP, Cornel MC, Henneman L. Challenges in the care for consanguineous couples: an exploratory interview study among general practitioners and midwives. BMC Fam Pract. 2012;13:105.  https://doi.org/10.1186/1471-2296-13-105.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Teeuw ME, Loukili G, Bartels EA, Ten Kate LP, Cornel MC, Henneman L. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society. Eur J Hum Genet. 2014;22:452–7.  https://doi.org/10.1038/ejhg.2013.167.CrossRefPubMedGoogle Scholar
  64. Ten Kate LP. Genetic risk. J Community Genet. 2012;3:159–66.  https://doi.org/10.1007/s12687-011-0066-9.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Ten Kate LP, Teeuw ME, Henneman L, Cornel MC. Consanguinity and endogamy in the Netherlands: demographic and medical genetic aspects. Hum Hered. 2014;77:161–6.  https://doi.org/10.1159/000360761.CrossRefPubMedGoogle Scholar
  66. Tucker EJ, Grover SR, Bachelot A, Touraine P, Sinclair AH. Premature ovarian insufficiency: new perspectives on genetic cause and phenotypic spectrum. Endocr Rev. 2016;37:609–35.  https://doi.org/10.1210/er.2016-1047.CrossRefPubMedGoogle Scholar
  67. Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiology. Clin Biochem. 2018;62:2–10.  https://doi.org/10.1016/j.clinbiochem.2018.03.012.CrossRefPubMedGoogle Scholar
  68. Vissers LELM, van Nimwegen KJM, Schieving JH, Kamsteeg EJ, Kleefstra T, Yntema HG, et al. A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Genet Med. 2017;19:1055–63.  https://doi.org/10.1038/gim.2017.1.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Whitney DK. Emotional sequelae of elective abortion: the role of guilt and shame. J Pastoral Care Counsel. 2017;71:98–105.  https://doi.org/10.1177/1542305017708159.CrossRefPubMedGoogle Scholar
  70. Zlotogora J, Carmi R, Lev B, Shalev SA. A targeted population carrier screening program for severe and frequent genetic diseases in Israel. Eur J Hum Genet. 2009;17:591–7.  https://doi.org/10.1038/ejhg.2008.241.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Martina C. Cornel
    • 1
    Email author
  • Selina Goodman
    • 2
  • Lidewij Henneman
    • 3
  1. 1.Department of Clinical Genetics, Amsterdam Public Health Research InstituteAmsterdam UMC, Vrije Universiteit AmsterdamAmsterdamThe Netherlands
  2. 2.College of Medicine and HealthUniversity of Exeter Medical SchoolExeterUK
  3. 3.Department of Clinical Genetics, Amsterdam Reproduction and Development Research InstituteAmsterdam UMC, Vrije Universiteit AmsterdamAmsterdamThe Netherlands

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