Congenital glaucoma of this type can result from both homozygous (25%) and compound heterozygous mutations (56%) in the CYP1B1 gene on chromosome 2 (2p22-p21) which codes for cytochrome P4501B1.
Evidence from many sources suggests that congenital glaucoma of this type is an autosomal recessive disorder. Parental consanguinity is common, the segregation ratio is approximately 25%, and the occurrence of congenital glaucoma among all offspring of two affected parents can be cited as support for this mode of inheritance. Many cases occur sporadically but this is consistent with expectations in small human sibships. Curiously, though, males are affected more often than females.
Another autosomal recessive infantile (congenital) glaucoma (600975), GLC3 or type B, is caused by mutations in GLC3B located at 1p36.2-p36.1. A third locus at 14q24.3 has also been proposed for GLC3, type C. Autosomal recessive primary congenital glaucoma (so-called) type D (613086) is caused by a mutation in LTBP2 located at 14q24 near the GLC3C locus and heterozygous mutations in TEK are responsible for type E (617272).
Other modes of inheritance have been described and, for now, this form of glaucoma, like others, has to be considered a genetically and clinically heterogeneous disorder pending additional genotyping. Early onset glaucoma is also a feature of numerous malformation and chromosomal disorders.