Skip to main content
PMC home page
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2000 Dec;57(12):793–804. doi: 10.1136/oem.57.12.793

Investigation of a cluster of children with Down's syndrome born to mothers who had attended a school in Dundalk, Ireland

G Dean 1, N Nevin 1, M Mikkelsen 1, G Karadima 1, M Petersen 1, M Kelly 1, J O'Sullivan 1
PMCID: PMC1739900  PMID: 11077007

Abstract

OBJECTIVES—To investigate a reported cluster of Down's syndrome in offspring of former pupils of a girls' school in Ireland, to establish the prevalence of Down's syndrome among live births in the area around the school, and to review the literature on the possible causes of reported clusters of Down's syndrome.
METHODS—Questionnaire survey of obstetric and personal histories of women who had attended the girls' school at Dundalk, County Louth, Republic of Ireland, at some time during 1956-7, and also of women who had attended another, nearby, girls' school during the same period. Comparison of observed numbers of cases of Down's syndrome identified by these surveys with maternal age adjusted expected numbers for the reported live births. Laboratory tests were conducted to verify and characterise the cases of Down's syndrome constituting the cluster. Retrospective collection and collation of data on Down's syndrome occurring among live births, and the compilation of maternal age specific incidences, in County Louth and in Newry and Mourne District in neighbouring Northern Ireland, during 1961-80. These rates were compared with reference rates and rates for other areas of Ireland.
RESULTS—Six children with Down's syndrome were confirmed among 387 reported live births to women who had been pupils at the girls' school in Dundalk during 1956-7, compared with 0.69 expected (nominal p<10-4). Five of the affected births were to mothers under 30 years of age, against 0.15 expected (nominal p<10-6), although only four of these mothers were attending the school at any one time. The origin of the non-disjunction was found to be maternal first meiotic in four children, mitotic after fertilisation in another (with the youngest mother), and in the remaining one could not be determined. The marked excess of Down's syndrome in births to young mothers did not extend to offspring of former pupils of the other Dundalk girls' school surveyed, or to live births in County Louth generally or in adjacent Newry and Mourne District.
CONCLUSION—A striking, highly localised, excess of Down's syndrome in births to young mothers who had attended a girls' school in Dundalk during 1956-57 has been confirmed. However, not all of the mothers of the affected children attended the school concurrently and the origin of non-disjunction in one child was an error occurring after conception. Some exposure essentially confined to girls attending the school at this time is a possible, although unlikely, explanation, but a review of potential risk factors does not suggest what this could be. Previous suggestions that an influenza epidemic or contamination from the Windscale nuclear reactor fire might be implicated, both of which occurred in October 1957, can be effectively dismissed because three of the women with affected offspring had left the school by then and had moved away from Dundalk, and Down's syndrome in the child of another mother originated in an error after fertilisation. Owing to the retrospective nature of the investigation and the characteristics of the cases, chance is the most likely explanation for the cluster.


Keywords: Down's syndrome; cluster; maternal exposure

Full Text

The Full Text of this article is available as a PDF (202.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. An unusual cluster of babies with Down's syndrome. Br Med J (Clin Res Ed) 1984 Jan 14;288(6411):146–147. doi: 10.1136/bmj.288.6411.146-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antonarakis S. E., Avramopoulos D., Blouin J. L., Talbot C. C., Jr, Schinzel A. A. Mitotic errors in somatic cells cause trisomy 21 in about 4.5% of cases and are not associated with advanced maternal age. Nat Genet. 1993 Feb;3(2):146–150. doi: 10.1038/ng0293-146. [DOI] [PubMed] [Google Scholar]
  3. Ballesta F., Queralt R., Gómez D., Solsona E., Guitart M., Ezquerra M., Moreno J., Oliva R. Parental origin and meiotic stage of non-disjunction in 139 cases of trisomy 21. Ann Genet. 1999;42(1):11–15. [PubMed] [Google Scholar]
  4. Bound J. P., Francis B. J., Harvey P. W. Down's syndrome: prevalence and ionising radiation in an area of north west England 1957-91. J Epidemiol Community Health. 1995 Apr;49(2):164–170. doi: 10.1136/jech.49.2.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown A. Role of radiation in aetiology of Down's syndrome. Br Med J (Clin Res Ed) 1984 Jan 14;288(6411):147–148. doi: 10.1136/bmj.288.6411.147-c. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burkart W., Grosche B., Schoetzau A. Down syndrome clusters in Germany after the Chernobyl accident. Radiat Res. 1997 Mar;147(3):321–328. [PubMed] [Google Scholar]
  7. Caldwell G. G. Twenty-two years of cancer cluster investigations at the Centers for Disease Control. Am J Epidemiol. 1990 Jul;132(1 Suppl):S43–S47. doi: 10.1093/oxfordjournals.aje.a115787. [DOI] [PubMed] [Google Scholar]
  8. Chakravarti A., Slaugenhaupt S. A. Methods for studying recombination on chromosomes that undergo nondisjunction. Genomics. 1987 Sep;1(1):35–42. doi: 10.1016/0888-7543(87)90102-9. [DOI] [PubMed] [Google Scholar]
  9. Chan A., McCaul K. A., Keane R. J., Haan E. A. Effect of parity, gravidity, previous miscarriage, and age on risk of Down's syndrome: population based study. BMJ. 1998 Oct 3;317(7163):923–924. doi: 10.1136/bmj.317.7163.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crick M. J., Linsley G. S. An assessment of the radiological impact of the Windscale reactor fire, October 1957. Int J Radiat Biol Relat Stud Phys Chem Med. 1984 Nov;46(5):479–506. doi: 10.1080/09553008414551711. [DOI] [PubMed] [Google Scholar]
  11. Cuckle H. S., Wald N. J., Thompson S. G. Estimating a woman's risk of having a pregnancy associated with Down's syndrome using her age and serum alpha-fetoprotein level. Br J Obstet Gynaecol. 1987 May;94(5):387–402. doi: 10.1111/j.1471-0528.1987.tb03115.x. [DOI] [PubMed] [Google Scholar]
  12. Dolk H., Nichols R. Evaluation of the impact of Chernobyl on the prevalence of congenital anomalies in 16 regions of Europe. EUROCAT Working Group. Int J Epidemiol. 1999 Oct;28(5):941–948. doi: 10.1093/ije/28.5.941. [DOI] [PubMed] [Google Scholar]
  13. Engel E. Autoantibodies and chromosomal aberrations. Lancet. 1967 Jun 10;1(7502):1271–1272. doi: 10.1016/s0140-6736(67)92736-5. [DOI] [PubMed] [Google Scholar]
  14. Fialkow P. J., Hecht F., Uchida I. A., Motulsky A. G. Increased frequency of thyroid autoantibodies in mothers of patients with Down's syndrome. Lancet. 1965 Oct 30;2(7418):868–870. doi: 10.1016/s0140-6736(65)92502-x. [DOI] [PubMed] [Google Scholar]
  15. Francis J., Snee M. A case control study of trisomy 21 and maternal pre-conceptual radiography. Clin Radiol. 1991 May;43(5):343–346. doi: 10.1016/s0009-9260(05)80545-8. [DOI] [PubMed] [Google Scholar]
  16. Glass A. G., Hill J. A., Miller R. W. Significance of leukemia clusters. J Pediatr. 1968 Jul;73(1):101–107. doi: 10.1016/s0022-3476(68)80045-9. [DOI] [PubMed] [Google Scholar]
  17. Grufferman S., Delzell E. Epidemiology of Hodgkin's disease. Epidemiol Rev. 1984;6:76–106. doi: 10.1093/oxfordjournals.epirev.a036276. [DOI] [PubMed] [Google Scholar]
  18. Gustafsson J., Annerén G., Ericsson U. B., Svanberg L., Ivarsson S. A. Thyroid antibodies are not a risk factor for pregnancies with Down syndrome. Prenat Diagn. 1995 May;15(5):451–454. doi: 10.1002/pd.1970150508. [DOI] [PubMed] [Google Scholar]
  19. Hook E. B., Carothers A. D. Use of computer simulation to evaluate a putative cluster of genetic or teratologic outcomes: adjustment for "multiple hypotheses" and application to a reported excess of Down's syndrome. Genet Epidemiol. 1997;14(2):133–145. doi: 10.1002/(SICI)1098-2272(1997)14:2<133::AID-GEPI3>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  20. Hook E. B., Topol B. B., Cross P. K. The natural history of cytogenetically abnormal fetuses detected at midtrimester amniocentesis which are not terminated electively: new data and estimates of the excess and relative risk of late fetal death associated with 47,+21 and some other abnormal karyotypes. Am J Hum Genet. 1989 Dec;45(6):855–861. [PMC free article] [PubMed] [Google Scholar]
  21. Huether C. A., Haroldson K., Ellis P. M., Ramsay C. N. Impact of prenatal diagnosis on revised livebirth prevalence estimates of Down syndrome in the Lothian region of Scotland, 1978-1992. Genet Epidemiol. 1996;13(4):367–375. doi: 10.1002/(SICI)1098-2272(1996)13:4<367::AID-GEPI5>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  22. Jacobs P., Dalton P., James R., Mosse K., Power M., Robinson D., Skuse D. Turner syndrome: a cytogenetic and molecular study. Ann Hum Genet. 1997 Nov;61(Pt 6):471–483. doi: 10.1046/j.1469-1809.1997.6160471.x. [DOI] [PubMed] [Google Scholar]
  23. Jaikrishan G., Andrews V. J., Thampi M. V., Koya P. K., Rajan V. K., Chauhan P. S. Genetic monitoring of the human population from high-level natural radiation areas of Kerala on the southwest coast of India. I. Prevalence of congenital malformations in newborns. Radiat Res. 1999 Dec;152(6 Suppl):S149–S153. [PubMed] [Google Scholar]
  24. Johnson Z., Lillis D., Delany V., Hayes C., Dack P. The epidemiology of Down syndrome in four counties in Ireland 1981-1990. J Public Health Med. 1996 Mar;18(1):78–86. doi: 10.1093/oxfordjournals.pubmed.a024466. [DOI] [PubMed] [Google Scholar]
  25. Kochupillai N., Verma I. C., Grewal M. S., Ramalingaswami V. Down's syndrome and related abnormalities in an area of high background radiation in coastal Kerala. Nature. 1976 Jul 1;262(5563):60–61. doi: 10.1038/262060a0. [DOI] [PubMed] [Google Scholar]
  26. Källén B., Karlsson P., Lundell M., Wallgren A., Holm L. E. Outcome of reproduction in women irradiated for skin hemangioma in infancy. Radiat Res. 1998 Feb;149(2):202–208. [PubMed] [Google Scholar]
  27. Källén K. Down's syndrome and maternal smoking in early pregnancy. Genet Epidemiol. 1997;14(1):77–84. doi: 10.1002/(SICI)1098-2272(1997)14:1<77::AID-GEPI6>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  28. Källén K. Parity and Down syndrome. Am J Med Genet. 1997 May 16;70(2):196–201. [PubMed] [Google Scholar]
  29. Lamb N. E., Freeman S. B., Savage-Austin A., Pettay D., Taft L., Hersey J., Gu Y., Shen J., Saker D., May K. M. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nat Genet. 1996 Dec;14(4):400–405. doi: 10.1038/ng1296-400. [DOI] [PubMed] [Google Scholar]
  30. Lechat M. F., Dolk H. Registries of congenital anomalies: EUROCAT. Environ Health Perspect. 1993 Jul;101 (Suppl 2):153–157. doi: 10.1289/ehp.93101s2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Little J. The Chernobyl accident, congenital anomalies and other reproductive outcomes. Paediatr Perinat Epidemiol. 1993 Apr;7(2):121–151. doi: 10.1111/j.1365-3016.1993.tb00388.x. [DOI] [PubMed] [Google Scholar]
  32. Mikkelsen M., Poulsen H., Grinsted J., Lange A. Non-disjunction in trisomy 21: study of chromosomal heteromorphisms in 110 families. Ann Hum Genet. 1980 Jul;44(Pt 1):17–28. doi: 10.1111/j.1469-1809.1980.tb00942.x. [DOI] [PubMed] [Google Scholar]
  33. Miller J. R., Baird P. A. Some epidemiological aspects of Down's syndrome in British Columbia. Br J Prev Soc Med. 1968 Apr;22(2):81–85. doi: 10.1136/jech.22.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Morris J. K., Alberman E., Mutton D. Is there evidence of clustering in Down syndrome? Int J Epidemiol. 1998 Jun;27(3):495–498. doi: 10.1093/ije/27.3.495. [DOI] [PubMed] [Google Scholar]
  35. O'Brien N., Crowley P. Downs syndrome and maternal age. Ir Med J. 1984 Jan;77(1):10–12. [PubMed] [Google Scholar]
  36. Olsen S. F., Martuzzi M., Elliott P. Cluster analysis and disease mapping--why, when, and how? A step by step guide. BMJ. 1996 Oct 5;313(7061):863–866. doi: 10.1136/bmj.313.7061.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. PLEYDELL M. J. Mongolism and other congenital abnormalities; an epidemiological study in Northamptonshire. Lancet. 1957 Jun 29;272(6983):1314–1319. doi: 10.1016/s0140-6736(57)91843-3. [DOI] [PubMed] [Google Scholar]
  38. Petersen M. B., Economou E. P., Slaugenhaupt S. A., Chakravarti A., Antonarakis S. E. Linkage analysis of the human HMG14 gene on chromosome 21 using a GT dinucleotide repeat as polymorphic marker. Genomics. 1990 May;7(1):136–138. doi: 10.1016/0888-7543(90)90531-x. [DOI] [PubMed] [Google Scholar]
  39. Petersen M. B., Schinzel A. A., Binkert F., Tranebjaerg L., Mikkelsen M., Collins F. A., Economou E. P., Antonarakis S. E. Use of short sequence repeat DNA polymorphisms after PCR amplification to detect the parental origin of the additional chromosome 21 in Down syndrome. Am J Hum Genet. 1991 Jan;48(1):65–71. [PMC free article] [PubMed] [Google Scholar]
  40. Puri B. K., Singh I. Season of birth in Down's syndrome. Br J Clin Pract. 1995 May-Jun;49(3):129–130. [PubMed] [Google Scholar]
  41. Ramsay C. N., Ellis P. M., Zealley H. Down's syndrome in the Lothian region of Scotland--1978 to 1989. Biomed Pharmacother. 1991;45(6):267–272. doi: 10.1016/0753-3322(91)90028-r. [DOI] [PubMed] [Google Scholar]
  42. Roman E., Doyle P., Ansell P., Bull D., Beral V. Health of children born to medical radiographers. Occup Environ Med. 1996 Feb;53(2):73–79. doi: 10.1136/oem.53.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rothman K. J. A sobering start for the cluster busters' conference. Am J Epidemiol. 1990 Jul;132(1 Suppl):S6–13. doi: 10.1093/oxfordjournals.aje.a115790. [DOI] [PubMed] [Google Scholar]
  44. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  45. Sever L. E., Gilbert E. S., Hessol N. A., McIntyre J. M. A case-control study of congenital malformations and occupational exposure to low-level ionizing radiation. Am J Epidemiol. 1988 Feb;127(2):226–242. doi: 10.1093/oxfordjournals.aje.a114799. [DOI] [PubMed] [Google Scholar]
  46. Sever L. E., Hessol N. A., Gilbert E. S., McIntyre J. M. The prevalence at birth of congenital malformations in communities near the Hanford site. Am J Epidemiol. 1988 Feb;127(2):243–254. doi: 10.1093/oxfordjournals.aje.a114800. [DOI] [PubMed] [Google Scholar]
  47. Sharp P. M., McConnell D. J. An unusual cluster of babies with Down's syndrome--was it caused by the Windscale fire? Br Med J (Clin Res Ed) 1984 Aug 11;289(6441):378–378. doi: 10.1136/bmj.289.6441.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sheehan P. M., Hillary I. B. An unusual cluster of babies with Down's syndrome born to former pupils of an Irish boarding school. Br Med J (Clin Res Ed) 1983 Nov 12;287(6403):1428–1429. doi: 10.1136/bmj.287.6403.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Shields L. M., Wiese W. H., Skipper B. J., Charley B., Benally L. Navajo birth outcomes in the Shiprock uranium mining area. Health Phys. 1992 Nov;63(5):542–551. doi: 10.1097/00004032-199211000-00005. [DOI] [PubMed] [Google Scholar]
  50. Sperling K., Pelz J., Wegner R. D., Schulzke I., Struck E. Frequency of trisomy 21 in Germany before and after the Chernobyl accident. Biomed Pharmacother. 1991;45(6):255–262. doi: 10.1016/0753-3322(91)90026-p. [DOI] [PubMed] [Google Scholar]
  51. Stoll C., Alembik Y., Dott B., Roth M. P. Study of Down syndrome in 238,942 consecutive births. Ann Genet. 1998;41(1):44–51. [PubMed] [Google Scholar]
  52. Stoller A., Collmann R. D. Area relationship between incidences of infectious hepatitis and of the births of children with Down's syndrome nine months later. J Ment Defic Res. 1966 Jun;10(2):84–88. doi: 10.1111/j.1365-2788.1966.tb00175.x. [DOI] [PubMed] [Google Scholar]
  53. Stolwijk A. M., Jongbloet P. H., Zielhuis G. A., Gabreëls F. J. Seasonal variation in the prevalence of Down syndrome at birth: a review. J Epidemiol Community Health. 1997 Aug;51(4):350–353. doi: 10.1136/jech.51.4.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Strigini P., Pierluigi M., Forni G. L., Sansone R., Carobbi S., Grasso M., Dagna Bricarelli F. Effect of x-rays on chromosome 21 nondisjunction. Am J Med Genet Suppl. 1990;7:155–159. doi: 10.1002/ajmg.1320370731. [DOI] [PubMed] [Google Scholar]
  55. Torfs C. P., van den Berg B. J., Oechsli F. W., Christianson R. E. Thyroid antibodies as a risk factor for Down syndrome and other trisomies. Am J Hum Genet. 1990 Oct;47(4):727–734. [PMC free article] [PubMed] [Google Scholar]
  56. Verger P. Down syndrome and ionizing radiation. Health Phys. 1997 Dec;73(6):882–893. doi: 10.1097/00004032-199712000-00001. [DOI] [PubMed] [Google Scholar]
  57. Yoon P. W., Freeman S. B., Sherman S. L., Taft L. F., Gu Y., Pettay D., Flanders W. D., Khoury M. J., Hassold T. J. Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of chromosomal error: a population-based study. Am J Hum Genet. 1996 Mar;58(3):628–633. [PMC free article] [PubMed] [Google Scholar]
  58. Zinn A. R. Growing interest in Turner syndrome. Nat Genet. 1997 May;16(1):3–4. doi: 10.1038/ng0597-3. [DOI] [PubMed] [Google Scholar]
  59. de Wals P., Bertrand F., de La Mata I., Lechat M. F. Chromosomal anomalies and Chernobyl. Int J Epidemiol. 1988 Mar;17(1):230–231. doi: 10.1093/ije/17.1.230. [DOI] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES