Investigating motile ciliopathies in a pediatric case of an abnormal optic nerve head

A congenital optic nerve head anomaly (CONHA) is an umbrella term for structurally abnormal optic nerve heads present at birth which may lead to vision loss. The potential roles of motile and non-motile ciliopathies in this process are not well understood. This report describes a pediatric case of CONHA and implicates a motile ciliopathy in a possible mechanism that affects embryogenesis of the optic nerve head.

A 21-month-old male with a normal prenatal and postnatal course, past medical history of recurrent upper and lower airway infections, and no known ocular history was referred by a community ophthalmologist for evaluation of a dysplastic optic disc. After the initial visit, fundus examination at a subsequent EUA revealed a hypoplastic macula and an anomalous nerve. Evaluation by a pulmonologist at 32 months due to multiple airway infections revealed atopic dermatitis and moderate persistent asthma. Primary ciliary dyskinesia was ruled out.

We theorize that this patient's fundus and systemic findings have a similar etiology. Differentiation of primary cilia on airway epithelial cells is known to produce motile cilia. We hypothesize that insults to a common cell may lead to disruption of three downstream pathways in our patient. The first line resulted in an atopic profile due to a disruption of motile ciliogenesis and mucociliary clearance. Second, disruption of primary cilia within the Sonic hedgehog pathway, a key regulator of neuronal development, may have resulted in a CONHA. Finally, the presence of abnormal primary cilia may have led to retinal dysplasia.

Linking systemic and ophthalmic findings can provide more insight into the role of motile cilia in other fundus conditions, allowing for targeted interventions. Thus, future research and gene therapy can work to prevent, or slow down, severe vision loss.