Clinical characteristics: Primary congenital glaucoma (PCG) is characterized by elevated intraocular pressure (IOP), enlargement of the globe (buphthalmos), edema, and opacification of the cornea with rupture of Descemet's membrane (Haab's striae), thinning of the anterior sclera and iris atrophy, anomalously deep anterior chamber, and structurally normal posterior segment except for progressive glaucomatous optic atrophy. Symptoms include photophobia, blepharospasm, and excessive tearing. Typically, the diagnosis is made in the first year of life. Depending on when treatment is instituted, visual acuity may be reduced and/or visual fields may be restricted. In untreated individuals, blindness invariably occurs.

Diagnosis/testing: The diagnosis of PCG is based on clinical criteria including: elevated IOP in a child typically before age one year, enlargement of the globe, increased corneal diameter, cloudy corneas, breaks in Decsemet’s membrane (Haab’s striae) and anomalously deep anterior chamber. Identification of biallelic pathogenic variants in CYP1B1 or LTBP2 or identification of a heterozygous pathogenic variant in TEK confirms the diagnosis if clinical features are inconclusive.

Management: Treatment of manifestations: Surgery (goniotomy, trabeculotomy, trabeculectomy, or deep sclerectomy) as early as possible; use of drainage implants or cyclodestruction if surgery fails; medication preoperatively and postoperatively to help control IOP; routine treatment of refractive errors and amblyopia.

Prevention of secondary complications: Discontinuation of medications such as Phospholine Iodide^® (echothiophate) before surgery to prevent prolonged apnea.

Surveillance: Lifelong monitoring to ensure control of IOP.

Agents/circumstances to avoid: Alpha-2 agonists because of risk for apnea and bradycardia.

Evaluation of relatives at risk: If the pathogenic variant(s) have been identified in the family, molecular genetic testing of at-risk sibs as soon as possible after birth in order to avoid repeated examinations under anesthesia in young children who do not have the pathogenic variant(s).

Genetic counseling: PCG caused by biallelic pathogenic variants in CYP1B1 or LTBP2 is inherited in an autosomal recessive manner. PCG caused by a heterozygous pathogenic variant in TEK is inherited in an autosomal dominant manner.

1. Autosomal recessive inheritance. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are asymptomatic; carrier testing for at-risk family members is possible if the pathogenic variants in the family are known.

2. Autosomal dominant inheritance. Each child of an individual with TEK-related PCG has a 50% chance of inheriting the pathogenic variant.

Prenatal testing for a pregnancy at increased risk is possible if the PCG-causing pathogenic variant(s) in the family are known.