CRB1-associated retinal dystrophy presenting as self-resolving opsoclonus and posterior uveitis

PURPOSE: To describe the unusual case of inflammatory CRB1-associated retinal dystrophy that initially presented with self-resolving opsoclonus. OBSERVATIONS: We report the case of a now 2-year-old female who developed opsoclonus without myoclonus at the age of 4 months. An extensive workup for neuroblastoma and other systemic diseases was unremarkable, and all unusual eye movements self-resolved at age 10 months. Twenty-one months after initial presentation, she began having reduced visual behaviors, and comprehensive ophthalmic exam at that time revealed recurrent saccadic intrusions as well as severe, chronic retinal inflammation and dystrophic changes. An extensive infectious and inflammatory workup was negative. Genetic sequencing revealed two variants in CRB1: a heterozygous missense mutation and a heterozygous novel deletion involving exon 12. The patient was treated with monthly infliximab and methylprednisolone infusions with improvement in her optic disc and macular capillary leakage. The patient's 8-month-old sister also harbored the same variants in CRB1 and had early signs of retinal dystrophy and peripheral vascular leakage on exam. CONCLUSION: Saccadic intrusions may be the first sign of a retinal dystrophy, and infants and children with this presentation should undergo a complete eye exam. We further highlight the link between CRB1-associated retinal dystrophy and inflammation, and how systemic steroids and tumor necrosis factor alpha (TNF-α) inhibitors may be effective therapies. Finally, we report a novel deletion in CRB1 that is likely highly penetrant.