A Peruvian Child with 18p-/18q+ Syndrome and Persistent Microscopic Hematuria

Abstract

Chromosome 18 pericentric inversion carriers could have offspring with recombinant chromosomes, leading to patients with clinical variable manifestations. Patients with 18p-/18q+ rearrangements share some clinical characteristics, while other characteristics differ. Factors for such divergence include the length of the inverted segment, among others. Here, we describe a Peruvian child with dysmorphic features, intellectual disability persistent microscopic hematuria, aortic pseudocoarctation, and descending aorta arteritis, among others. Karyotype analysis of family members determined the mother as the carrier of a pericentric inversion: 18[inv(18)(p11.2q21.3)]. This child carries a recombinant chromosome 18, with chromosomal microarray analysis detecting two genomic imbalances in patient's chromosome 18: one duplicated region and one deleted segment in the large and the short arms, respectively. Persistent microscopic hematuria has not been reported among 18p-/18q+ phenotypes. Our patient elucidates that other factors play significant and yet unknown roles for not fulfilling the proposed genotype-phenotype correlation associated with hemizygosity in this type of recombinant chromosome 18 or presenting these features as the patient ages.

Keywords: chromosome 18 pericentric inversion; genotype–phenotype correlation; hematuria; microarray analysis; recombinant chromosome 18.

Fig. 1

Diagram of inversion loop model depicting the crossing-over during meiosis between an abnormal chromosome with pericentric inversion and its normal homolog. The event within the loop crossover produces two recombinant chromosomes: one with duplicated segment of a long arm segment and the other with duplicated segment of a short arm region.

Fig. 2

Phenotypic features of the Peruvian child aged 6 years and 7 months with the 18p-/18q+ rearrangement.

Fig. 3

Diagnostic images showing patient's anomalies. ( A ) Brain magnetic resonance imaging (MRI) on T1 (sagittal view) and T2 (axial and coronal views) sequences show white matter lesions noted as small spots on white matter. ( B ) Persistent patent ductus arteriosus and descending aorta walls thickening. ( C ) Aortic arch bulging and kinking suggesting aortic pseudocoarctation and dilated supra-aortic brachiocephalic branches.

Fig. 4

Chromosomal findings in the mother and the proband using conventional karyotype (left) and schematic figures (right). Red arrows highlight abnormal chromosomes. The mother carries a pericentric inverted segment, whereas the proband has inherited a recombinant chromosome 18.

Fig. 5

Pedigree showing karyotypes of family members. Karyotype analysis could not be performed on miscarriages. yo: years old; mo: months old, inv: chromosomal inversion, rec: recombinant chromosome. Black arrow signals the proband.

Fig. 6

Results of copy number variants in the present case using GeneChip CytoScan 750K Array protocols (Affymetrix) showing a duplication at 18q22.1q23(62,142,135–78,013,728)x3 and a deletion at 18p11.32p11.21(136,227–11,246,728)x1. At the top line, red and blue boxes denote signal loss and gain of chromosomal material, respectively.

Fig. 7

Pericentric inverted segments of chromosome 18 leading to offspring with recombinants. Our patient rearrangement is depicted in the box with loss (red) and gain (blue) of regions. Other reported carriers with schematic inverted segments are shown in the right, whose offspring demonstrates recombinants with altered phenotypes. Black: inverted segment, green: cases with molecular analysis for chromosomal region confirmation (fluorescent in situ hybridization [FISH] or arrays analysis).