Analysis of invdupdel(8p) rearrangement: Clinical, cytogenetic and molecular characterization

Abstract

Inverted duplication 8p associated with deletion of the short arms of chromosome 8 (invdupdel[8p]) is a relatively uncommon complex chromosomal rearrangement, with an estimated incidence of 1 in 10,000-30,000 live borns. The chromosomal rearrangement consists of a deletion of the telomeric region (8p23-pter) and an inverted duplication of the 8p11.2-p22 region. Clinical manifestations of this disorder include severe to moderate intellectual disability and characteristic facial features. In most cases, there are also CNS associated malformations and congenital heart defects. In this work, we present the cytogenetic and molecular characterization of seven children with invdupdel(8p) rearrangements. Subsequently, we have carried out genotype-phenotype correlations in these seven patients. The majority of our patients carry a similar deletion but different size of duplications; the latter probably explaining the phenotypic variability among them. We recommend that complete clinical evaluation and detailed chromosomal microarray studies should be undertaken, enabling appropriate genetic counseling.

Prenatal diagnosis of inverted duplication deletion 8p syndrome mimicking trisomy 18

“…In the present case, the deletion/duplication did not include the GATA4 gene; however, the duplication size was one of the largest that has ever been reported. Two previous studies reported a correlation between increased duplication length and severity of cognitive deficits [Fisch et al, ; García‐Santiago et al, ]. In this case, we can speculate that large duplication length may be associated with CHD that was uncharacteristically severe for this disorder.…”

“…Invdupdel[8p] is a well‐described and uncommon chromosomal rearrangement with an incidence rate of around 1 in 10,000–30,000 liveborn infants [García‐Santiago et al, ]. In this case, we present the first known prenatal diagnosis of an invdupdel[8p] syndrome complicated with polyvalvuvar dysplasia and central nervous system (CNS) abnormalities.…”

“…It is already known that in the inverted duplication/deletion 8p syndrome, structural abnormalities manifest, in descending order of frequency: CNS malformations (including agenesis of the corpus callosum), skeletal abnormalities, hypotonia, and congenital heart defects [García‐Santiago et al, ]. In literature, about 50 cases of invdupdel[8p] have been reported in the postnatal period [Sireteanu et al, ].…”

Prenatal Diagnosis of a Retroesophageal Left Brachiocephalic Vein: Two Case Reports

“…The parental karyotype and chromosomal microarray results were normal. The 8p inverted duplication and deletion were associated with congenital heart disease, a hypoplastic corpus callosum, facial dysmorphisms, intellectual disability, autism, hypotonia, and epilepsy . Termination of pregnancy was performed at 23 weeks.…”

De Novo San Luis Valley Syndrome-like der(8) Chromosome With a Concomitant dup(8p22) in a Mexican Girl

“…2). Actually, a previous patient's rearrangement [9] resulted from a mechanism seemingly unrelated to OR clusters. In another subject, the reportedly inverted 8p duplication was not proven [7], and in still another [8], there was an 8p triplication instead of duplication.…”