CACNA1F-related synaptic dysfunction: challenges diagnosing congenital stationary night blindness presenting without...

To describe pediatric patients with CACNA1F-associated incomplete X-linked congenital stationary night blindness presenting without nyctalopia, and review the causes leading to diagnosis delay.

Retrospective cohort.

This was set in a single institution between 2004 and 2019. There were12 patients. The intervention or observation procedures used were clinical course, visual acuity, refractive error, images, electrophysiology, genetic testing, pedigree. The main outcome measures were cohort description and causes of diagnosis delay.

For these 12 cases, the referring diagnosis was congenital nystagmus (7), reduced best-corrected visual acuity (BCVA, 4), and progressive myopia (1). Nyctalopia was not a presenting symptom and developed in 4 patients during follow-up. Seven patients presented with nystagmus. All patients developed early-onset myopia. Myopia progressed more rapidly before age 6 than after (average 1.14 D vs 0.25 D) (p = 0.0033). The average final BCVA was 20/50 (20/30-20/150). Vision at presentation was correlated with final visual acuity (r² = 0.87, p = 5.4E-06). The first cycloplegic refraction was correlated to the final refractive error (r² = 0.49, p = 0.009). Patients with nystagmus had worse BCVA on average. Full-field electroretinogram was abnormal and diagnostic in all cases, as confirmed by genetic testing. The average time to diagnosis was 4.2 years, and the average age at diagnosis was 7.9 years. The delay in diagnosis was due to the absence of nyctalopia, not performing an electroretinogram and/or an alternative diagnosis.

In children, CACNA1F-associated synaptic dysfunction does not usually present with night blindness. It should be suspected in male patients with early-onset myopia, especially with a history of nystagmus.