Discrepancies in cytogenetic results between different tissues in two fetuses with Wolf- Hirschhorn syndrome

Abstract

Discrepant unbalanced structural chromosome aberrations between placental and fetal tissue, both involving the short arm of chromosome 4, were found in two human fetuses affected with Wolf-Hirschhorn syndrome. In the first instance, placental chromosome examination revealed a del(4) (p14), whereas fetal fibroblast chromosomes showed an unbalanced der(4)t(4;13)(p14;q11) translocation. In the second instance, placental karyotyping revealed a 4p+ chromosome, while amniocytes showed a submicroscopic deletion at 4p16.3. Since confirmation of structural aberrations from placental tissue is mostly not sought if the phenotype of the fetus is abnor- mal, discrepancies between karyotypes obtained from placental tissue and amniocytes or fetal tissues might be more frequent than the rare reports published so far would suggest. It is unclear whether the simple deletion or the more complex rearrangement is the primary aberration from which the other derived. Structural chromosome aberrations often have a much more complex mechanism of formation than the end product would suggest, and secondary rearrangements of a given aberration in the zygote are more frequent than expected.

Prenatal diagnosis of Wolf-Hirschhorn syndrome confirmed by comparative genomic hybridization array: report of two cases and review of the literature

“…The ultrasonographic presentation of WHS with IUGR and a notch on the uterine artery also overlap with previously described case by Levaillant et al [15], while oligohydramnios as a unique finding or associated with other fetal malformations has also been reported in fetuses with WHS [20-24]. A wide range of other anatomical abnormalitites as renal hypoplasia, skeletal dysplasias, hypospadias, diaphragmatic hernia, single umbilical artery also complicates these cases with variable incidence [7,25-31]. In addition, craniofacial dysmorphic features such as microcephaly, "Greek warrior helmet" profile (the broad high nasal bridge continuing to the forehead), prominent glabella, high arched eyebrows and hypertelorism are strongly evocative of WHS [7,26,32,33].…”

Unique mosaicism of structural chromosomal rearrangement: Is chromosome 18 preferentially involved?

“…We have found 14 published cases involving chromosome 18; this chromosome appears to be most frequently involved in these structural rearrangements (Table II). As far as we know, only a few articles describe cases involving other chromosomes (chromosome 2 [Wyandt et al, 1982], chromosomes 2 and 14 [Engelen et al, 2000], chromosome 4 [Pescia et al, 1982; Smeets et al, 1998; Doco‐Fenzy et al, 1999; Schinzel, 2000; Syrrou et al, 2001], chromosome 5 [Perfumo et al, 2000], chromosome 8 [Van Balcom et al, 1992], chromosome 9 [Leung and Rudd, 1988], chromosome 11 [Pettenati et al, 1993; Tharapel et al, 1999], chromosome 13 [Fryns et al, 1979; Jalal et al, 1990; Duckett et al, 1992], chromosome 17 [Scriven and Docherty, 1992], and X chromosome [Pettenati et al, 1993]). The general “gene poverty” of chromosome 18 [International Human Genome Sequencing Consortium, 2001] could explain why this chromosome appears to be most frequently involved in structural rearrangement mosaicisms that are compatible with life.…”

“…There are few descriptions of mosaicisms of two unbalanced cell lines, and they mostly concern intra chromosomal duplication/deletion for the same chromosomal region. Inter chromosomal reciprocal translocations coexisting as two or more different (unbalanced) cell lines are even less frequent [Scriven and Docherty, 1992; Pettenati et al, 1993; Smeets et al, 1998; Doco‐Fenzy et al, 1999; Schinzel, 2000].…”

Prenatal Sonographic Patterns in Six Cases of Wolf-Hirschhorn (4p–) Syndrome

“…There is indeed the possibility of false negative cytogenetic diagnoses after first trimester chorionic villous sampling [47], with a typical deletion visible later on amniocytes in some pregnancies with a characteristic abnormal ultrasound at 22 WG. The adequate diagnosis may also be missed at genetic amniocentesis because only 58% of cases affected by WHS can be recognized on regular G-banding karyotypes [2,48,49].…”