Recurrence rate for de novo 21q21q translocation Down syndrome: A study of 112 families

Abstract

Recurrence of de novo GqGq Down syndrome (DS) in nine reported families and the low frequency of this chromosome abnormality in the population prompted this multicenter study to examine recurrence rate. Pedigrees and cytogenetic findings were analyzed from 112 families ascertained by a DS child with de novo GqGq translocation. Four of 112 sets of parents had abnormal cytogenetic findings. One mother and two fathers had a low proportion of mosaicism for trisomy 21 in peripheral lymphocytes. In one of these fathers, fibroblast studies confirmed the mosaicism (others not similarly studied). Two of these three families have one additional child each, both being normal. In the fourth family, the mother is heterozygous for a pericentric inversion of chromosome 21. Ninety of the 112 probands had a total of 130 full sibs and 34 half sibs. None of these 164 sibs was affected; the recurrence rate could still be as high as 2% (with 95% confidence based upon calculation of a one-tailed confidence interval). Because of the latter, the nine reports of recurrence in the literature, and the abnormal cytogenetic findings in peripheral lymphocytes in 4/112 sets of parents (3.6%), we think that caution should be exercised when counseling that the recurrence risk of this event is remote.

Trisomy 21 mosaicism in gonads with unexpectedly high recurrence risks

“…A parental mosaic for (21;21) translocation has also been pointed out by Hall [1985], who suggested analysing additional cells because 1% maternal mosaicism was detected in a mother of 2 children with translocation (21;21). Steinberg et al [1984] described a low proportion of mosaicism for trisomy 21 in lymphocytes of 3 of 224 parents of a DS child with de novo (21;21) translocation. The mosaicism found in 2 couples out of 6 certainly proves the necessity of extensive parental cytogenetic study after a second pregnancy with trisomy 21; this has also been affirmed by Couzin et al [1987].…”

Management of subsequent pregnancy after an unexplained stillbirth

“…45 In the absence of a parental translocation, these aneuploidies impart an empirical recurrence risk of less than 5%, but the risk can be as high as 18% in some cases depending on the age of the women. [46][47][48][49] Invasive karyotyping by chorion villus sampling or amniocentesis obviously increases the risk of early pregnancy loss, so care must be taken in giving such advice to younger women. In case investigation of a previous stillbirth did not include an attempt at karyotyping, or in case attempted karyotyping failed, young women should be offered a risk estimation using combined first trimester screening (such as nuchal translucency measurement, nasal bone ossification and PAPP-A/hCG biochemistry), with resort to formal karyotyping if indicated by the results of the screening.…”

Clusters of identical new mutation in the evolutionary landscape

“…(F) c = 8. al., 1995;Levinson et al, 1990;Mackenzie & Penrose, 1951;Mohrenweiser, 1994;Puck et al, 1995;Steinberg et al, 1984;Wallis et al, 1990;van Essen et al, 1992). In humans, these premeiotic mutation events, which include base-pair changes, deletions, duplications, insertions, chromosome rearrangements, trinucleotide repeats, and aneuploidy, are often called germinal mosaics (a list of at least 80 additional references on germinal mosaics in humans can be obtained from the authors).…”