CBL syndrome presenting with severe EBV infection and panuveitis masquerade

Purpose To describe a case of CBL syndrome presenting with life-threatening pediatric Epstein-Barr virus (EBV) infection and sight-threatening rod-cone dystrophy (RCD) masquerading as severe panuveitis. Methods Single case report with results of whole-exome sequencing (WES) analysis in the proband and his parents. Data were collected from July 2009 to December 2022. Results A 35-month-old boy presented with severe primary EBV infection complicated by encephalitis and hemophagocytic lymphohistiocytosis. The clinical picture abated with systemic corticosteroids. Genetic testing revealed a heterozygous germline pathogenic variant in the CBL gene c.1141T > G (p.Cys381Gly). At 6 years old, he developed a severe bilateral panuveitis requiring multiple lines of immunosuppressants, mostly to control refractory cystoid macular edema (CME). During follow-up, intraretinal pigment deposits and peripheral retinal atrophy started to appear. Full-field electroretinogram (ffERG) revealed a pattern consistent with RCD. Repeat WES targeting known inherited retinal disease (IRD) genes was negative. A diagnosis of CBL syndrome complicated by RCD masquerading as severe bilateral panuveitis was made, and CME treatment was switched to oral acetazolamide. Conclusions CBL syndrome can present with severe EBV infection early in life. RCD masquerading as severe panuveitis is also a possible feature of CBL syndrome. RCD should be kept in mind in patients with this syndrome who present with idiopathic intraocular inflammation and are refractory to IMT. Carbonic anhydrase inhibitors (CAI) should be tried early to treat CME.