Risk of Parents Who Have Had One Child With Down's Syndrome (Mongolism) Having Another Child Similarly Affected

Carter, C.O.; Evans, Kerry

doi:10.1016/s0140-6736(61)91085-6

Cited by 80 publications

(20 citation statements)

References 5 publications

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“…This suggests somatic mosaicism for trisomy 21 in the parents and possibly a concomitant presence of mosaicism in the ovary. In addition, the recurrence risk of trisomy 21 to a sibling is elevated, particularly for young mothers ( Carter and Evans 1961; Richards 1977; Stene et al 1984). In a few families examined by ovarian biopsy, trisomic cell lines in the ovaries have been detected ( Nielsen et al 1988; Tseng et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Modeling the maternal‐age dependency of reproductive failure and genetic fitness

Zheng

Guo

Byers

2000

Evolution and Development

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The offspring of older parents are at a higher risk of suffering low birth weights and congenital birth defects that result from mutations and chromosomal anomalies. When the defect is paternal in origin, it often can be shown that the primary lesion arose during mitotic proliferation of the spermatogonial germ cell population. By contrast, germline mosaicism is seldom invoked to explain the age dependency of maternally derived aberrations because germline proliferation in the ovary is already completed during fetal development. Age-dependent defects of maternal origin might, however, be explained in part by the progressive loss of oocytes during the mother's reproductive life. A large number of oocytes undergo the initial stages of maturation each month, but typically only one completes maturation and is ovulated while the majority are discarded, probably by an apoptotic mechanism. Here we explore the possibility that the monthly choice of oocytes to undergo maturation is influenced by subtle phenotypic characters of those oocytes that may bear genetic defects such as trisomy 21. We have generated a mathematical model to describe the loss kinetics for such mutant oocytes relative to the overall pool of resting oocytes, and we assess evolutionary strategies that would favor their utilization faster than, at the same rate as, or slower than the normal oocytes. This formulation reveals that the slower-rate scheme would effectively diminish the utilization of mutant oocytes in young mothers but would increase the risk of related birth defects for older mothers. Accordingly, we propose that natural selection should have favored the delayed utilization of defective oocytes in a primitive high-mortality culture, but that this evolutionary strategy would be outmoded for modern society, because it would lead to an increased frequency of birth defects for older mothers.

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Section: Discussionmentioning

confidence: 99%

Modeling the maternal‐age dependency of reproductive failure and genetic fitness

Zheng

Guo

Byers

2000

Evolution and Development

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“…Because the frequency of mongolism increases with increasing inaternal age (Penrose, 1933) it is assumed that the non-disjunction generally occurs during formation of the egg, rather than the sperm. Mongolism arising in this way is characteristically non-familial, the risk of recurrence in a subsequent child of the same parents being substantially the same as that for any mother of the same age (Carter and Evans, 1961). For a minority of parents of mongoloid children, however, the risk of recurrence in a subsequent child is substantially increased, for one of several possible reasons:…”

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confidence: 99%

Two Unusual Cases of Familial Mongolism

Dallaire¹,

Fråser²

1964

Can. J. Genet. Cytol.

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“…As there is no indication of mosaicism in either parent, though this cannot be entirely excluded, the most likely reason for the birth of the twins in this case would be due to a chance event which is matemal-age dependant. The random risk for a mother aged 39 giving birth to a child with Down's syndrome lies between 1/260 and 1/100 (Carter and Evans, 1961), and the empirical recurrence risk approximately double this, though this may be increased for concurrent births due to environmental factors. The chance of dizygous twins being born in this country is approximately 1/100 (Carter, 1969), but this increases with maternal age and is expected to be approximately 1 in 60 in this case.…”

Section: Discussionmentioning

confidence: 99%