PCG with biallelic CYP1B1 and CPAMD8 variants: a longitudinal case report

Primary congenital glaucoma (PCG) is a rare developmental disorder caused by dysgenesis of the trabecular meshwork and anterior chamber angle. We report a five-year longitudinal case of severe bilateral PCG in a male presenting at two months of age with photophobia, tearing, corneal edema, and markedly elevated intraocular pressure (IOP). The patient required four surgical interventions, including deep sclerectomy with mitomycin C and trabeculotomy ab externo, to achieve long-term IOP control. Serial axial length measurements documented rapid buphthalmos, and ultrasound biomicroscopy revealed progressive posterior staphyloma, peripheral anterior synechiae, and iris thinning consistent with anterior segment dysgenesis (ASD). Whole exome sequencing identified compound heterozygosity: CYP1B1 c.182G>A (p.G61E), the well-characterized Saudi founder mutation for PCG, and CPAMD8 c.3061G>A (p.V102M), a novel ultra-rare variant predicted to be damaging. The coexistence of these two heterozygous variants in genes affecting complementary anterior segment developmental pathways supports a digenic inheritance model. To our knowledge, this is the first reported case of combined CYP1B1 and CPAMD8 variants in congenital glaucoma, underscoring the value of comprehensive genetic analysis in severe or atypical pediatric glaucoma presentations.