Duplication of chromosome region 4q28.3-qter in monozygotic twins with discordant phenotypes

Abstract

We describe monozygotic twins with partially discordant phenotypes who were found to have a duplication of chromosome region 4q28.3-qter. The duplicated region of chromosome 4 resulted from an unbalanced segregation of a balanced maternal (4;22)(q28.3;p13) translocation. Duplication of the long arm of chromosome 4 has been described in >60 patients; however, it usually results from the unbalanced segregation of a parental balanced translocation and has an associated monosomy. Twenty cases of dup 4q without an associated monosomy have been reported, and this is the only case of dup 4q28. 3-qter. All cases of dup 4q are reviewed, and phenotypic aspects are analyzed. Issues of monozygotic twinning and other birth defects also are addressed.

A DUPLICATION dup(4)(q28q35.2) DE NOVO IN A NEWBORN

“…Clinical and cytogenetic data are not currently sufficient to delineate a well-defined dup(4q) syndrome. Reviews of the literature 4-7 and the recent report 2 confirm the phenotypic variability accompanying duplicated long arm of chromosome 4. The wide phenotypic variability frequently reported in cases of duplication 4q could be related to the different size of the duplicated region, the location of the breakpoints and associated monosomies of the other chromosomal parts.…”

“…The duplicated region is relatively large and overlaps other previously reported cases. Celle et al 2 described monozygotic twins with partially discordant phenotypes and the duplication 4q28.3→qter, originated from the unbalanced maternal translocation t(4;22)(q28.3;p13). Thus our patient is the second case with the same partial trisomy and the first description of pure duplication without associated monosomy 1,2 .…”

“…Duplication of the long arm of chromosome 4 has been already described in more than 60 patients 1,2 . Most of them result from the meiotic segregation of a parental balanced translocation and associate with a partial monosomy of various segments of other chromosomes.…”

“…Patients with partial trisomy 4q have variable clinical stigmatization, which is both related to the size of duplicated segment of the chromosomal arm 4q and to specific associated monosomy. A review of the literature 2 revealed approximately 20 cases of a pure duplication of 4q spanning the region from q12 to q35. Although simple or pure forms of duplications are less common they serve as a basis for a better understanding of relationships between chromosomal anomalies and their clinical manifestations.…”

Pathologic Genomic Rearrangements in Idiopathic Mentally Retarded Patients from Iran

“…Of the more than 90 genes that may be deleted in 22q13.3 deletion syndrome (Phelan-McDermid syndrome), the majority of the neurological features are thought to be caused by haploinsufficiency of SHANK3 [22] which is deleted in patient 3 too. 4q duplication is a rare condition that usually presents with MR and multiple abnormalities, including microcephaly, malformed ears, flat nasal bridge, tooth and thumb anomalies [23,24], most of which are shared by patient 4.…”