8q21.11 microdeletion in two patients with syndromic peters anomaly

Abstract

Peters anomaly is a form of anterior segment dysgenesis characterized by central ocular opacity and corneo-lenticular adhesions. Isolated and syndromic Peters anomaly can be observed and demonstrate significant genetic heterogeneity. We report the identification of overlapping 8q21.11 deletions in two patients with syndromic Peters anomaly via whole exome sequencing and chromosomal microarray analyses. Microdeletions of 8q21.11 were recently reported in 10 patients with highly variable phenotypes involving craniofacial features, ptosis, intellectual disability, abnormalities of the hands/feet and other defects; sclerocornea and/or microphthalmia were reported in three cases. The two additional cases presented in this report expand the phenotypic spectrum of 8q21.11 microdeletions to include Peters anomaly (seen in both patients) and persistent primary dentition (seen in one patient with a larger deletion). The two novel deletions include the ZFHX4 and PEX2 genes, which were also affected in all three previous cases involving ocular anomalies. Screening of the remaining alleles of ZFHX4 and PEX2 did not identify any additional likely pathogenic variants in either patient, suggesting a dominant mechanism (haploinsufficiency) for the identified deletion. This report provides further insight into the phenotypes associated with 8q21.11 deletions and, for the first time, reports Peters anomaly as an additional ocular feature; screening for copy number variations of the 8q21.11 region should be considered in patients with Peters anomaly and related syndromic features. © 2016 Wiley Periodicals, Inc.

Keywords: 8q21.11 microdeletion; PEX2; Peters anomaly; ZFHX4; copy number variation.

Figure 1

Facial photographs of Patient 1 in infancy (A) and at 6 years of age (B). Please note corneal opacities in infancy with partial clearing later, high forehead, cupid’s bow upper lip, and prominent low-set ears.

Figure 2

Schematic drawing of 8q21 deletions in affected cases. The UCSC Genome Browser (http://genome.ucsc.edu) view of the 8q21 region indicating positions of genes and deletions observed in each patient (red bars; chromosome 8 coordinates (hg19) for each deleted region are indicated below).