Three cases of congenital fixed dilated pupils due to smooth muscle dysfunction

The authors report the cases of three patients with congenital fixed dilated pupils with the same genetic mutation. Congenital fixed dilated pupils are rare and should alert ophthalmologists to the possibility of the coexistence of systemic life-threatening disorders like thoracic aortic aneurysms and dissections, early coronary artery disease and strokes.

Congenital fixed dilated pupils (congenital mydriasis) is characterized by hypoplasia or aplasia of the iris muscles, with absence of iris between the collarette and pupillary border, creating a scalloped pupillary margin. All affected individuals carry a p.R179H heterozygous mutation in the ACTA2 gene.

These three cases were three female teenagers with congenital fixed dilated pupils observed since birth associated with progressive neurological deterioration and smooth muscle cell dysfunction. They all tested positive for the genetic mutation.

They had severe clinical manifestations early in life, including patent ductus arteriosus in the first year of life, and aortic or great vessel aneurysms or dissections in the first two decades of life.

One patient had a stroke with a hemiparesis at age 2, while another developed dystonia and dysarthria at age 5. No neurological abnormalities were detected in the third patient until the age of 16, although cerebral MRI showed chronic ischemic white matter changes. The patients also experienced altered function of other smooth muscle cell-dependent organs.