Iris anomalies and the incidence of ACTA2 mutation

Background Central cysts of the iris pigment epithelium, or iris flocculi, are frequently reported in the literature in association with thoracic aortic aneurysm and dissection due to smooth muscle alpha-actin 2 ( ACTA2 ) mutations. Children with ACTA2 mutations may also present with congenital mydriasis. We report our experience regarding the frequency of ACTA2 mutation in children with the above iris anomalies. Methods This is a retrospective, consecutive case series of all children presenting for iris flocculi or congenital mydriasis at a single tertiary centre from October 2012 to December 2016. Results 13 children with iris flocculi and 3 with congenital mydriasis presented during the study period. 10 children with iris flocculi completed genetic testing, and none were positive for ACTA2 mutation. All children with congenital mydriasis presented with a multisystem smooth muscle dysfunction syndrome; two of these three children tested positive for missense R179 ACTA2 mutations. Conclusions In this series, ACTA2 mutation or copy number variation was not detected in children presenting for iris flocculi, whereas congenital mydriasis was associated with R179 mutation in both cases that tested positive for ACTA2 mutation. The case of congenital mydriasis without typical cardiac features of the R179 ACTA2 phenotype or intracranial vasculopathy was negative for ACTA2 mutation. While all children presenting with these iris anomalies should be offered a genetic evaluation, incidence data should inform genetic counselling, particularly in the absence of a family history of aneurysm or sudden death, or systemic signs of smooth muscle dysfunction.