First non-mosaic case of isopseudodicentric chromosome 18 (psu idic(18)(pter → q22.1::q22.1 → pter) is associated with multiple congenital anomalies reminiscent of trisomy 18 and 18q- syndrome

Isopseudodicentric chromosome 18 is very rare and results in a combination of partial trisomy and partial monosomy of chromosome 18. We report here a hypotrophic newborn with a lateral cleft lip and palate and multiple craniofacial dysmorphisms, a combined heart defect, unilateral hypoplasia of the kidney, bilateral aplasia of thumbs, and generalized contractures. Cytogenetic analysis revealed an isopseudodicentric chromosome 18 with breakpoint in 18q (46,XX,psu idic(18)(pter → q22.1::q22.1 → pter)). The isopseudodicentric chromosome 18 was observed in 100% of blood lymphocytes and umbilical cord fibroblasts, thus indicating a non-mosaic finding of the isopseudodicentric chromosome in the child. An elongated derivative chromosome 18 had also been found prenatally in amniotic cells. In contrast, a terminal deletion (18q-) was detected in placental cell cultures. The breakpoint was mapped to a 0.9 Mb region on 18q22.1 (located 64.8-65.7 Mb from the telomere of the p-arm) by a novel quantitative PCR approach with SYBR green detection. The results indicate an identical breakpoint of the isopseudodicentric chromosome 18 in the child and the 18q- chromosome in the placenta. To our knowledge this is the first report that a fetus carrying an isopseudodicentric chromosome 18 with breakpoint in 18q (46,XX,psu idic(18)(pter → q22.1::q22.1 → pter)) in non-mosaic form can be viable, but is associated with severe congenital malformations of the child.