Ophthalmological phenotype associated with biallelic CPAMD8 variants: first report in Mexican patients

Introduction Anterior segment dysgenesis is a heterogeneous group of developmental conditions affecting the anterior segment of the eye. These could have a significant impact on vision due to development of secondary childhood glaucoma. Their classification is complex due to genetic and clinical heterogeneity. Variants in the CPAMD8 gene have been shown to result in abnormalities such as cataract, iris hypoplasia, and ectopia lentis.Methods We described two unrelated Mexican patients with anterior segment dysgenesis in whom novel biallelic variants in the CPAMD8 gene were identified. Their phenotype included bilateral iris hypoplasia, ectropion uvea, zonular anomalies, and secondary childhood glaucoma.Results Whole-exome sequencing identified variants in the CPAMD8 gene. These variants included one novel homozygous pathogenic variant in the first patient—NM_015692.5(CPAMD8):c.367_388dup—and two novel variants in a compound heterozygous state—NM_015692.5(CPAMD8):c.2276+1G>A and NM_015692.5(CPAMD8):c.4478T>A—in the second patient.Discussion The literature review revealed that the most frequent manifestations associated with CPAMD8 variants are congenital cataract, iris hypoplasia, zonular abnormalities (including phacodonesis and ectopia lentis), and secondary childhood glaucoma (67%). Although the phenotype is heterogeneous, the analysis of CPAMD8 should be recommended in patients with anterior segment dysgenesis or secondary childhood glaucoma associated with non acquired ocular anomalies as the aforementioned alterations.