Chromosome 22q11.2 Deletion Syndrome Associated with Sclerocornea

Sclerocornea Gil Binenbaum, Brian J. Forbes, Donna M. McDonald-McGinn, William V Anninger; Children’s Hospital of Philadelphia, Philadelphia, PA Introduction: The chromosome 22q11.2 deletion syndrome encompasses disorders previously called DiGeorge Syndrome (DGS) (85% have the deletion), velocardiofacial syndrome (VCFS) (100% have the deletion), Takao (conotruncal-anomaly-face) syndrome, and CATCH syndrome. Clinically, 22q11.2 deletion is characterized by congenital heart anomalies, thymus and parathyroid hypoplasia with T-cell deficiency and hypocalcemia, palatal abnormalities, characteristic facial dysmorphisms, and learning difficulties. We present six 22q11.2 patients with sclerocornea, a finding previously unreported in the literature. Methods: Multicenter case series. Results: Four boys and two girls were identified with sclerocornea, systemic DGS/VCFS findings, and fluorescence in situ hybridization (FISH)-confirmed microdeletion at chromosome 22q11.2. FISH diagnosis was perinatal in five cases but at 2 years of age in one child. Sclerocornea was bilateral in five patients. Findings included descemetocele (five eyes), microophthalmos (one eye), iridocorneal adhesions (one bilateral case), and severe anterior segment dysgenesis (one eye). Two patients underwent bilateral penetrating keratoplasty (PKP); a third was scheduled for unilateral PKP. Follow-up ranged from 2 to 30 months. Discussion: Reported ocular findings in 22q11.2 deletion have included posterior embryotoxon, retinal vascular tortuosity, eyelid hooding, strabismus, and astigmatism. Sclerocornea is a novel finding; it suggests that a genetic locus at 22q11.2 may be involved in anterior segment embryogenesis. In most of our cases, the diagnostic process was underway, but in one patient 22q11.2 deletion was not suspected until after the child had already been undergoing treatment for sclerocornea for 2 years. Conclusions: Sclerocornea should be added to the clinical manifestations of the 22q11.2 deletion syndrome. Ophthalmologists diagnosing sclerocornea in children with systemic findings suggestive of 22q11.2 deletion should ensure appropriate genetic referral.