Some pediatric glaucomas are inherited and have known genetic mutations associated with them. Genetic testing and counseling should be considered for parents of pediatric glaucoma patients and for adults with onset of glaucoma in childhood or early adulthood (see Table 1-2 in Chapter 1 of this volume).
Primary Congenital Glaucoma
Although most cases of PCG occur sporadically, a familial pattern of inheritance is seen in 10%–40% of cases. The inheritance is usually autosomal recessive with incomplete or variable penetrance. Higher rates of familial inheritance are seen in children from the Middle East and central Europe. Patients with a family history consistent with autosomal recessive inheritance should be screened for mutations in CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), especially if there is a history of consanguinity in the family. Small families also should be considered for screening; the case may only appear to be “sporadic” because there are too few family members to discern the inheritance pattern. The CYP1B1 gene encodes an enzyme thought to be important in anterior segment development and regulation of aqueous humor secretion.
Another gene that has been associated with PCG is LTBP2 (latent transforming growth factor beta-binding protein 2) within the GLC3C locus. Other mutations of this gene are associated with Weill-Marchesani syndrome and microspherophakia. Mutations in ANGPT1 (angiopoietin-1) or TEK (tunica interna endothelial cell kinase, the receptor for ANGPT1, also known as TIE2) are inherited in an autosomal dominant pattern, result in loss of protein function that affects the development of Schlemm canal, and can lead to PCG.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.