Overlapping Phenotypes in Congenital Ocular Malformations and the Importance of Molecular Testing

Exome Sequencing in a Swiss Childhood Glaucoma Cohort Reveals CYP1B1 and FOXC1 Variants as Most Frequent Causes

“…The two families in our cohort carrying FOXC1 duplications add to cases of FOXC1-associated Axenfeld-Rieger spectrum with development of glaucoma at a young age, whereas patient 5 [II:1] with the frameshift variant may be classified as a "FOXC1-associated primary congenital glaucoma or as "ARS with PCG". 4 The prevalence of CYP1B1 pathogenic variants in our cohort was comparable to other European populations. 17,19,38 Previous studies investigated the prevalence of FOXC1 pathogenic variants among childhood glaucoma patients.…”

“…The two families in our cohort carrying FOXC1 duplications add to cases of FOXC1- associated Axenfeld-Rieger spectrum with development of glaucoma at a young age, whereas patient 5 [II:1] with the frameshift variant may be classified as a “ FOXC1 -associated primary congenital glaucoma or as “ARS with PCG”. 4 …”

“…3 Variable presence of ocular features of ARS such as iris processes, posterior embryotoxon, corectopia, and iris hypoplasia, may cause the clinical distinction from PCG to be challenging. 4 Type and incidence of childhood glaucoma varies according to population studied and degree of parental consanguinity (e.g. the incidence of PCG ranges from 1:1250 to 1:30,000).…”

“…3 Variable presence of ocular features of ARS such as iris processes, posterior embryotoxon, corectopia, and iris hypoplasia, may cause the clinical distinction from PCG to be challenging. 4 …”