Recombinant Down syndrome: a case report and literature review

Abstract

We report a case of a child with features of Down syndrome (DS) but with an atypical karyotype. Initial chromosome analysis was 46,XX,dup(21q).ish 21(wcp21+). The father's chromosomes were normal. However, the mother was found to have mosaicism for a pericentric inversion of chromosome 21 (19/30 cells). The revised chromosome result of the child was 46,XX,rec(21)dup(21q)inv(21)(p12q21.1)mat. A literature review of similar cases (hereafter referred to as rec dup(21q)) was conducted to aid counselling about recurrence risks and the prognosis for this child. All previous reports of rec dup(21q) were secondary to a maternal pericentric inversion. Male carriers did not seem to be at risk of having offspring with the rec dup(21q), although the number of male carriers was limited. In those with rec dup(21q), the risk of congenital heart disease was similar to that of trisomy 21. In reported cases, the facial appearance was suggestive of Down syndrome but perhaps less striking. Although the data are limited, there is an indication the developmental disabilities and short stature are milder in those with rec dup(21q) compared to trisomy 21. These observations promote the concept that the region of chromosome 21 proximal to the duplication contains genetic information contributing to the expression of some features of Down syndrome.

Mental retardation, congenital heart malformation, and myelodysplasia in a patient with a complex chromosomal rearrangement involving the critical region 21q22

“…Most patients carry a full trisomy 21, whereas in 4% of the patients, phenotype is secondary to other chromosomal rearrangements resulting in partial chromosome 21 trisomy [Lazzaro et al, 2001]. A ''DS critical chromosomal region'' (DSCR) has been described.…”

Sperm studies in heterozygote inversion carriers: a review

“…Many cases of recombinant progeny from pericentric inversion carriers have been reported in the literature (Ishii et al, 1997;Mejia-Baltodano et al, 1997;Goodman et al, 1999;Angle et al, 2000;Dufke et al, 2000;Ilgin Ruhi et al, 2001;Lazzaro et al, 2001;Battaglia et al, 2002;Garcia-Heras and Martin, 2002;Lagier-Tourenne et al, 2004). The viability of the recombinant products mostly depends on the genetic content (and so the size) of the noninverted segment because they are the potential regions to be deleted or duplicated by recombination.…”

A Rare Case of Pericentric Inversion, Inv (21) (p12;q22) in Repeated PregnancyLoss: A Case Report

“…The first case of pericentric inversion of one chromosome 21 was reported by Gray et al 6 Since then, at least 15 cases of this inversion have been reported. [7][8][9][10][11][12][13][14][15][16] The low frequency of inverted chromosome 21 described in the literature is probably due to the small size of the chromosome. 1 In all cases previously reported, with the exception of two case ascertained after four miscarriages and another case was diagnosed by infertility, 12,16 while our patient was ascertained after three miscarriages, other cases were referred for Down's syndrome in offspring resulting from miotic recombination in the inverted segment.…”