Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin

Abstract

An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc.

Interstitial deletion 2p11.2–p12: Report of a patient with mental retardation and review of the literature

“…We have listed the clinical manifestations of the six previously published patients with deletions in 2p11.2–p12 and of our patient in Table I [Prasher et al, 1993; Los et al, 1994; Wenger and McPherson, 1997; Lacbawan et al, 1999; Barber et al, 2005]. Apart from developmental delay/mental retardation, there were no other consistent findings which would allow the delineation of a clinically recognizable 2p11.2–p12 deletion syndrome.…”

“…Interstitial deletions of chromosome bands 2p11.2–p12 are rare, and only six patients have been reported to date [Prasher et al, 1993; Los et al, 1994; Wenger and McPherson, 1997; Lacbawan et al, 1999; Barber et al, 2005]. These patients had developmental delay/mental retardation and variable additional problems such as hypospadias, facial dysmorphisms, club foot or Wilms tumor (Table I).…”

The Variant inv(2)(p11.2q13) Is a Genuinely Recurrent Rearrangement but Displays Some Breakpoint Heterogeneity

“…Unbalanced recombinant products involving an inv(2)(p11.2q13) are very rare and have involved crossing-over adjacent to, rather than within, the inverted segment. 18,19 Typing of microsatellites outside the inverted segment showed that recombination suppression appeared to extend for variable distances beyond the breakpoints (table 5). Two of the group C families shared the same haplotype well beyond the inversion breakpoints, particularly on proximal 2p.…”

Characterization of Brain Malformations in the Baraitser-Winter Syndrome and Review of the Literature

“…The same chromosomal anomaly, maternally inherited, had been previously report-ed in a boy showing some clinical similarities to this patient [1,15]. Although such chromosomal inversion can occur in healthy individuals [9,15], the author hypothesized the possible occurrence in these two patients of cryptic unbalanced aberrations involving chromosome 2, causally related to the maternally inherited inversion [15]. Indeed, a chromosome 2 interstitial deletion associated with a paternally inherited pericentric inversion (2)(p11.2 q13) has been subsequently reported in a child with dysmorphic features, developmental delay, sensorineural hearing loss, and hypotonia [9].…”