Down Syndrome Incidence

Table 1. Incidence of conceiving a first child with Down syndrome based on maternal age. (years)1
  Estimated probability: 
Down syndrome occurs with an estimated frequency of 1 in 600 live births and 1 in 150 conceptions2, with an estimated live birth male/female sex ratio of 1.158. About ½ of all abnormal chromosomal karyotypes involve trisomy for all or part of the chromosome 2112. About 80% of trisomy 21 conceptions result in pregnancy loss4. After amniocentesis confirmed trisomy 21, 10.2% of the pregnancies ended fetal demise15. From the National Down Syndrome Cytogenetic Register (1989-1996) between the time of chorionic villus sampling and term an estimated 43% of pregnancies ended in a miscarriage or still birth, between the time of amniocentesis and term an estimated 23% of pregnancies ended in a miscarriage or still birth, and 12% of births were stillborn or resulted in a neonatal death16. The USA prevalence is highest in Hispanics and lowest in African Americans3. As many as 80% of all infants with Down syndrome are born to women under the age of 359, as most pregnancies occur in women of younger ages. DNA polymorphic analysis shows that 5% account for the paternal origin of nondisjunction6. The diagnosis of Down syndrome is not always made at birth, in one study,11 only 74% ultimately identified as having Down syndrome were recognized within the first six months.

In general, the chance of having a second child with Down syndrome (without taking age into account) is 1% in each subsequent pregnancy. Parents of children with translocations must have a chromosomal analysis to assess actual future risk. Translocations can be sporadic or inherited, and the recurrence risk for subsequent pregnancies can only be calculated when both parents have a karyotype10. See Table 2 and 3.
Table 2. Chances of recurrence of Down syndrome5
Type of Down syndrome Parents' chromosomes     Chance of recurrence
Trisomy 21 Normal 1 in 100 if mother < 40. If mother > 40, twice usual chance for her age (see Table 1)
Translocation with chromosome 13, 14, 15, or 22 Normal Usual chance for mother's age (see Table 1)
Mother a carrier
Father a carrier		 1 in 8
1 in 40
Translocation with another chromosome 21 Normal Usual chance for mother's age (see Table 1)
Either parent a carrier 100%
Mosaicism Normal Unknown, probably the usual chance for mother's age (see Table 1)


Table 3. Empiric Risks* for Down Syndrome Live Birth7
Source Risk
Young mother with previous Trisomy 21 live birth, miscarriage or stillbirth About 1%
Occurance of Trisomy 21 in 2nd- or 3rd-degree relative; maternal age < 35     Somewhat increased but still less than 1%
Rare families with two or more cases of Trisomy 21 Risk markedly increased for 1st- and 2nd-degree relatives
Mother with 21/13, 21/14 or 21/15 translocation About 15%
Father with 21/13, 21/14 or 21/15 translocation About 5%
Mother with 21/22 translocation About 10%
Father with 21/22 translocation About 12%
Either parent with 21/21 translocation 100%
*Maternal-age specific risks not included.

Men with Down syndrome can father a child, the first fully documented case in literature being in 198914, the second reported in 1994 in Germany16, and the third, a 26-year-old man with confirmed nonmosaic trisomy 21, fathering a "normal" son17.
A woman with Down syndrome conceiving with a "normal" male has a 10% theoretical chance (the reported rate is 48%) of having a child with Down syndrome, since half of the woman's eggs would have an extra chromosome, but approximately 80% of pregnancies where the fetus has Down syndrome would be expected to end in spontaneous miscarriage. Bovicelli et al. (1982) comprehensively reviewed reports of 30 pregnancies in 26 women with Down syndrome between 1917 and 1982. The outcome of the pregnancies was 10 babies with Down syndrome, 17 "normal" (6 had mental or physical retardation or nonspecific congenital malformations) and 3 abortions or stillbirths. In the 15 cases of known or supposed paternity, 8 fathers were mentally retarded and the remaining 7 were close relatives of the women with Down syndrome. There is an additional case from Finland, not reviewed by Bovicelli, of a "normal" son born to a mother with Down syndrome and a 63-year-old father (Kivimäki and Lagus (1981)13.
References:
1. Hook E & Chambers GM Birth Defects, 13 (3a): 123, 1997. Revised: December 18, 2007.
2. Antonfarakis SE, Peterson MB, McInnis MG, et al. The meiotic stage of nondisjunction in trisomy 21: determination by using DNA polymorphisms. Am J Hum Genet 1992;5:1411-6.
3. Down syndrome prevalence at birth—United States, 1983-1990.. Teratology 1997;56:31-6.
4. Freeman S, Grantham M, Hassold T, et al.Cytogenetic and molecular studies of spontaneous human abortions. Am J Hum Genet 1996;49(suppl);916A(abstr).
5. Selikowitz, M Down Syndrome: The facts, 2nd Ed., 1997, p. 177.
6. Antonfarakis SE and the Down Syndrome Collaborative Group. Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DNA polymorphims. N Engl J Med 1991;324:872-6.
7. Berini RB and Kahn E (Eds.), Clinical Genetics Handbook, 1987.
8. Huether CA, Martin RL, Stoppelman SM, D'Souza S, Bishop JK, Torfs CP, Lorey F, May KM, Hanna JS, Baird PA, Kelly JC. Sex ratios in fetuses and liveborn infants with autosomal aneuploidy. Am J Med Genet 1996 Jun 14;63(3):492-500.
9. Cooley WC, Graham JM. Down syndrome: An update and review for the primary physician. Clin Pediatr 1991 30:233.
10. Cohen WI. Health care in the neonatal period in Caring for Individuals with Down Syndrome and their Families, Report of the Third Ross Roundtable on Critical Issues in Family Medicine. Columbus, OH: Ross Products Division, Abbott Laboratories, 1995, 16.
11. Shapiro BL. The environmental basis of the Down syndrome phenotype. Dev Med Child Neurol 1994 36:84.
12. Thuline HC. 1984. Rare Chromosomal Findings in Down's Syndrome in Berg JM (Ed.) Perspectives and Progress in Mental Retardation Vol. II—Biomedical Aspects, p. 159. Baltimore: University Park Press.
13. Cited in Tuck CM, Bennett JW, Varela M. 1984. Down's Syndrome and Familial Aneuploidy in Berg JM (Ed.) Perspectives and Progress in Mental Retardation Vol. II—Biomedical Aspects, p. 168. Baltimore: University Park Press.
14. Sheridan R, Llerena J, Matkins S, Debenham, P, Cawood, A & Bobrow, M. Fertility in a male with trisomy 21. Journal of Medical Genetics 1989 26:5.
15. Morris JK, Wald NJ, Watt HC. Fetal loss in Down syndrome pregnancies. Prenat Diagn 1999 Feb 19(2):142-5.
16. Zuhlke C, Thies U, Braulke I, Reis A, Schirren C. Down syndrome and male fertility: PCR-derived fingerprinting, serological and andrological investigations. Clin Genet 1994 Oct 46 (4): 324-6.
17. Pradhan M, Dalal A, Khan F, Agrawal S. Fertility in men with Down syndrome: A case report.. Fertil Steril 2006 Dec 86 (6): 1765.
Compiled by Victor J. Bishop