Fragile X Syndrome Secondary to in Vitro Fertilization with a Family Egg Donor, A Case Report and Review of the Literature
,
Abstract
Objective: To evidence the need for screening fragile X syndrome (FXS) in egg donors in assisted reproduction protocols.
Case report: This is the report of a boy with FXS who inherited the mutated allele from an ovule donated by the mother´s sister through an assisted reproduction protocol. Identifying premutation (PM) carriers of FXS amongst gamete donors isn’t part of the obligatory genetic analysis for donors and is only considered by most of the in vitro fertility societies and guidelines as part of the extension screening tests.
Conclusion: It is cost-effective to do pre-conceptional screening for the PM or full mutation (FM) of the FMR1 gene affected in FXS in every woman undergoing assisted reproductive methods, including gamete donors even without a positive family history of intellectual disabilities. This case supports the need of rethinking the guidelines on the necessary gamete donor screening tests in assisted reproduction protocols.
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11. Karimov CB, Moragianni VA, Cronister A, Srouji S, Petrozza J, Racowsky C, et al. Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function. Hum Reprod. 2011; 26: 2077–83.
12. Hunter J, Rivero-arias O, Angelov A, Kim E, Fotheringham I, Leal J. Epidemiology of Fragile X Syndrome: A Systematic Review and Meta-Analysis. Am J Med Genet A. 2014; 164A: 1648-58.
13. Saldarriaga W, Forero-Forero JV, González-Teshima LY, Fandiño-Losada A, Isaza C, Tovar-Cuevas JR, et al. Genetic cluster of fragile X syndrome in a Colombian district. J Hum Genet 2018; 63: 509–16.
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16. American Society for Reproductive Medicine. Appendix A: Minimal genetic screening for gamete donors. Fertil Steril 2004; 82 Suppl 1: S22–3.
17. Committee Opinion No. 691: Carrier Screening for
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18. Wirojanan J, Angkustsiri K, Tassone F, Gane LW, Hagerman RJ. A girl with fragile X premutation from sperm donation. Am J Med Genet A 2008; 146A: 888-92.
19. Saldarriaga-Gil W, Tascon Ospina E, Herrera-Castañeda E. Fecundation in vitro in Fragile X syndrome. Case report. Chilean Journal of Obstetrics and Gynecology 2020; 85: 654–61.
20. Cronister A, Teicher J, Rohlfs EM, Donnenfeld A, Hallam S. Prevalence and instability of fragile X alleles: Implications for offering fragile X prenatal diagnosis. Obstet Gynecol 2008; 111: 596–601.
21. Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K. Prevalence of carriers of premutation-size alleles of the FMR1 gene - and implications for the population genetics of the fragile X syndrome. Am J Hum Genet 1995; 57: 1006–18.
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23. Berkenstadt M, Ries-Levavi L, Cuckle H, Peleg L, Barkai G. Preconceptional and prenatal screening for fragile X syndrome: Experience with 40 000 tests. Prenat Diagn 2007; 27: 991–4.
24. Jang JH, Lee K, Cho EH, Lee EH, Kim JW, Ki CS. Frequency of FMR1 premutation carriers and rate of expansion to full mutation in a retrospective diagnostic FMR1 Korean sample. Clin Genet 2014; 85: 441–5.
25. Hung CC, Lee CN, Wang YC, Chen CL, Lin TK, Su YN, et al. Fragile X syndrome carrier screening in pregnant women in Chinese Han population. Sci Rep 2019; 9: 15456.
26. Hantash FM, Goos DM, Crossley B, Anderson B, Zhang K, Sun W, et al. FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United Statesi. Genet Med 2011; 13: 39–45.
27. Ryynänen M, Heinonen S, Makkonen M, Kajanoja E, Mannermaa A, Pertti K. Feasibility and acceptance of screening for fragile X mutations in low-risk pregnancies. Eur J Hum Genet 1999; 7: 212–6.
28. Toledano-Alhadef H, Basel-Vanagaite L, Magal N, Davidov B, Ehrlich S, Drasinover V, et al. Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet 2001; 69: 351–60.
29. Ma Y, Wei X, Pan H, Wang S, Wang X, Liu X, et al. The prevalence of CGG repeat expansion mutation in FMR1 gene in the northern Chinese women of reproductive age. BMC Med Genet 2019; 20: 81.
30. Castilla JA, Abellán F, Alamá P, Aura M, Bassas L, Clúa E, et al. Genetic screening in gamete donation: Recommendations from SEF, ASESA, AEBM-ML, ASEBIR and AEGH. Medicina Reproductiva y Embriología Clínica 2020; 7: 1–4.
31. Dondorp W, De Wert G, Pennings G, Shenfield F, Devroey P, Tarlatzis B, et al. ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues. Hum Reprod 2014; 29: 1353–9.
32. Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Recommendations for gamete and embryo donation: a committee opinion. Fertil Steril 2013; 99: 47-62.e1.
33. Saldarriaga W, Tassone F, González-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R. Fragile X syndrome. Colomb Med (Cali) 2014; 45: 190–8.
34. Pastore LM, Christianson MS, McGuinness B, Vaught KC, Maher JY, Kearns WG. Does theFMR1 gene affect IVF success? Reprod Biomed Online 2019; 38: 560-9.
35. Musci TJ, Caughey AB. Cost-effectiveness analysis of prenatal population-based fragile X carrier screening. Am J Obstet Gynecol 2005; 192: 1905-12; discussion 1912-5.
36. Zhang L, Bao Y, Riaz M, Tiller J, Liew D, Zhuang X, et al. Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis. Genet Med 2019; 21: 1958–68.
37. Johansen Taber K, Lim- Harashima J, Naemi H, Goldberg J. Fragile X syndrome carrier screening accompanied by genetic consultation has clinical utility in populations beyond those recommended by guidelines. Mol Genet Genomic Med 2019; 7: e1024.
38. van der Riet AA, van Hout BA, Rutten FF. Cost effectiveness of DNA diagnosis for four monogenic diseases. J Med Genet 1997; 34: 741-5.
39. Song FJ, Barton P, Sleightholme V, Yao GL,
Fry-Smith A. Screening for fragile X syndrome: A literature review and modelling study. Health Technol Assess 2003; 7: 1-106.
2. Bracewell-Milnes T, Saso S, Abdalla H, Thum MY.
A systematic review investigating psychosocial aspects of egg sharing in the United Kingdom and their potential effects on egg donation numbers. Hum Fertil (Camb) 2018; 21: 163-173.
3. ACOG Committee Opinion No. 469: Carrier screening for fragile X syndrome. Obstet Gynecol 2010; 116: 1008-10.
4. ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol 2011; 117: 1028-31.
5. 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.
6. Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Recommendations for gamete and embryo donation: a committee opinion. Fertil Steril 2013; 99: 47-62.e1.
7. Association of Biomedical Andrologists; Association of Clinical Embryologists; British Andrology Society; British Fertility Society; Royal College of Obstetricians and Gynaecologists. UK guidelines for the medical and laboratory screening of sperm, egg and embryo donors (2008). Hum Fertil (Camb) 2008; 11: 201-10.
8. Clarke H, Harrison S, Perez MJ, Kirkman-Brown J. UK guidelines for the medical and laboratory procurement and use of sperm, oocyte and embryo donors (2019). Hum Fertil (Camb) 2019; 6: 1-13.
9. Saldarriaga W, Tassone F, González-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R. Fragile X syndrome. Colomb Med (Cali) 2014; 45: 190-8.
10. Sullivan SD, Welt C, Sherman S. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med 2011; 29: 299-307.
11. Karimov CB, Moragianni VA, Cronister A, Srouji S, Petrozza J, Racowsky C, et al. Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function. Hum Reprod. 2011; 26: 2077–83.
12. Hunter J, Rivero-arias O, Angelov A, Kim E, Fotheringham I, Leal J. Epidemiology of Fragile X Syndrome: A Systematic Review and Meta-Analysis. Am J Med Genet A. 2014; 164A: 1648-58.
13. Saldarriaga W, Forero-Forero JV, González-Teshima LY, Fandiño-Losada A, Isaza C, Tovar-Cuevas JR, et al. Genetic cluster of fragile X syndrome in a Colombian district. J Hum Genet 2018; 63: 509–16.
14. Rollins JD, Collins JS, Holden KR. United States Head Circumference Growth Reference Charts: Birth to
21 Years. J Pediatr 2010; 156: 907-13. e2.
15. World Health Organization. WHO child growth standards: head circumference-for-age, arm circumference-for-age, triceps skinfold-for-age and subscapular skinfold-for-age: methods and development, 2007.
16. American Society for Reproductive Medicine. Appendix A: Minimal genetic screening for gamete donors. Fertil Steril 2004; 82 Suppl 1: S22–3.
17. Committee Opinion No. 691: Carrier Screening for
Genetic Conditions. Obstet Gynecol. 2017; 129: e41-e55.
18. Wirojanan J, Angkustsiri K, Tassone F, Gane LW, Hagerman RJ. A girl with fragile X premutation from sperm donation. Am J Med Genet A 2008; 146A: 888-92.
19. Saldarriaga-Gil W, Tascon Ospina E, Herrera-Castañeda E. Fecundation in vitro in Fragile X syndrome. Case report. Chilean Journal of Obstetrics and Gynecology 2020; 85: 654–61.
20. Cronister A, Teicher J, Rohlfs EM, Donnenfeld A, Hallam S. Prevalence and instability of fragile X alleles: Implications for offering fragile X prenatal diagnosis. Obstet Gynecol 2008; 111: 596–601.
21. Rousseau F, Rouillard P, Morel ML, Khandjian EW, Morgan K. Prevalence of carriers of premutation-size alleles of the FMR1 gene - and implications for the population genetics of the fragile X syndrome. Am J Hum Genet 1995; 57: 1006–18.
22. Dombrowski C, Lévesque S, Morel ML, Rouillard P, Morgan K, Rousseau F. Premutation and intermediate-size FMR1 alleles in 10 572 males from the general population: Loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet 2002; 11: 371–8.
23. Berkenstadt M, Ries-Levavi L, Cuckle H, Peleg L, Barkai G. Preconceptional and prenatal screening for fragile X syndrome: Experience with 40 000 tests. Prenat Diagn 2007; 27: 991–4.
24. Jang JH, Lee K, Cho EH, Lee EH, Kim JW, Ki CS. Frequency of FMR1 premutation carriers and rate of expansion to full mutation in a retrospective diagnostic FMR1 Korean sample. Clin Genet 2014; 85: 441–5.
25. Hung CC, Lee CN, Wang YC, Chen CL, Lin TK, Su YN, et al. Fragile X syndrome carrier screening in pregnant women in Chinese Han population. Sci Rep 2019; 9: 15456.
26. Hantash FM, Goos DM, Crossley B, Anderson B, Zhang K, Sun W, et al. FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United Statesi. Genet Med 2011; 13: 39–45.
27. Ryynänen M, Heinonen S, Makkonen M, Kajanoja E, Mannermaa A, Pertti K. Feasibility and acceptance of screening for fragile X mutations in low-risk pregnancies. Eur J Hum Genet 1999; 7: 212–6.
28. Toledano-Alhadef H, Basel-Vanagaite L, Magal N, Davidov B, Ehrlich S, Drasinover V, et al. Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet 2001; 69: 351–60.
29. Ma Y, Wei X, Pan H, Wang S, Wang X, Liu X, et al. The prevalence of CGG repeat expansion mutation in FMR1 gene in the northern Chinese women of reproductive age. BMC Med Genet 2019; 20: 81.
30. Castilla JA, Abellán F, Alamá P, Aura M, Bassas L, Clúa E, et al. Genetic screening in gamete donation: Recommendations from SEF, ASESA, AEBM-ML, ASEBIR and AEGH. Medicina Reproductiva y Embriología Clínica 2020; 7: 1–4.
31. Dondorp W, De Wert G, Pennings G, Shenfield F, Devroey P, Tarlatzis B, et al. ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues. Hum Reprod 2014; 29: 1353–9.
32. Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Recommendations for gamete and embryo donation: a committee opinion. Fertil Steril 2013; 99: 47-62.e1.
33. Saldarriaga W, Tassone F, González-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R. Fragile X syndrome. Colomb Med (Cali) 2014; 45: 190–8.
34. Pastore LM, Christianson MS, McGuinness B, Vaught KC, Maher JY, Kearns WG. Does theFMR1 gene affect IVF success? Reprod Biomed Online 2019; 38: 560-9.
35. Musci TJ, Caughey AB. Cost-effectiveness analysis of prenatal population-based fragile X carrier screening. Am J Obstet Gynecol 2005; 192: 1905-12; discussion 1912-5.
36. Zhang L, Bao Y, Riaz M, Tiller J, Liew D, Zhuang X, et al. Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis. Genet Med 2019; 21: 1958–68.
37. Johansen Taber K, Lim- Harashima J, Naemi H, Goldberg J. Fragile X syndrome carrier screening accompanied by genetic consultation has clinical utility in populations beyond those recommended by guidelines. Mol Genet Genomic Med 2019; 7: e1024.
38. van der Riet AA, van Hout BA, Rutten FF. Cost effectiveness of DNA diagnosis for four monogenic diseases. J Med Genet 1997; 34: 741-5.
39. Song FJ, Barton P, Sleightholme V, Yao GL,
Fry-Smith A. Screening for fragile X syndrome: A literature review and modelling study. Health Technol Assess 2003; 7: 1-106.
| Files | ||
| Issue | Vol 15, No 2 (June 2021) | |
| Section | Case Reports | |
| DOI | https://doi.org/10.18502/jfrh.v15i2.6455 | |
| Keywords | ||
| In Vitro Techniques Fertility Fragile X Syndrome Genetic Testing | ||
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How to Cite
1.
González- Teshima L, Payán-Gómez C, Saldarriaga W. Fragile X Syndrome Secondary to in Vitro Fertilization with a Family Egg Donor, A Case Report and Review of the Literature. J Family Reprod Health. 2021;15(2):130-135.
