OMIM ID:
Glaucoma, Congenital Primary A
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This may be the most common type of early (infantile, congenital) glaucoma. Elevated intraocular pressure may be present at birth but sometimes is not evident until the first year of life or in some cases even later. Irritability, photophobia, and epiphora are early signs. The globe is often buphthalmic, the cornea is variably cloudy, and breaks in the Descemet membrane (Haab striae) may be present. Frequently the iris root is inserted anteriorly in the region of the trabecular meshwork. The anterior chamber often appears abnormally deep. Early reports of a membrane covering the angle structures have not been confirmed histologically. The mechanism causing elevated IOP seems to be excessive collagen tissue in the anterior chamber angle that impedes normal aqueous outflow. The pressure is usually in the range of 25-35 mmHg but this is variable as the course can be intermittent. It should be considered a bilateral disease although about one-fourth of patients have only unilateral elevations of pressure even though trabecular abnormalities are present.
Optic cupping may begin temporally but the more typical glaucomatous cupping eventually occurs.
Systemic Features
No consistent systemic abnormalities are associated with primary congenital glaucoma. However, it is important to note that glaucoma is a feature of many congenital malformation syndromes and chromosomal aberrations.
Genetics
Inheritance
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.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.