Primary Congenital Glaucoma - Glaucoma


Indications for Testing

  • Cornea clouding – in infant or child
  • Persistent red eye – test family members of affected child for carrier status
  • Carrier screening – for other family members when a causative CYP1B1 mutation is identified
  • Prenatal testing – for at-risk pregnancies in families where the causative CYP1B1 mutations are known

Laboratory Testing

  • CYP1B1 gene sequencing
    • Gene occurrence in congenital glaucoma
      • Familial – 20-100%
      • Nonfamilial – 10-15%
    • Absence of mutations does not necessarily rule out carrier status or the presence of disease

Differential Diagnosis

  • Corneal edema or opacity
  • Corneal enlargement
    • Axial myopia
    • Hereditary megalocornea
    • Keratoglobus
  • Epiphora and red eye
    • Conjunctivitis
    • Corneal abrasion
    • Uveitis
    • Keratitis
  • Photophobia

Clinical Background

Glaucoma is the second leading cause of blindness in the world and the leading cause of blindness among Africans Americans. Primary congenital glaucoma (PCG) is the most common childhood glaucoma. A notable subtype, newborn PCG, may often have the most severe and clinically challenging expression. Mutations in the CYP1B1 gene are responsible for >50% of cases in some populations.


  • Birth prevalence
    • 1/5,000-22,000 in western countries
    • 1/2,500 in Middle Eastern countries
    • 1/2,500 in Slovakian Romani populations
    • 1/3,300 in Andhra Pradesh state of India
  • Age – infancy
  • Sex
    • M>F, 3:1 in U.S.
    • M<F, 2:3 in Japan


  • Autosomal recessive inheritance of mutations in the CYP1B1 gene
    • Homozygosity – predictive of disease
    • Heterozygosity – carrier status; carriers are unaffected


  • Abnormality of trabecular meshwork creates an abnormal filtration angle
  • Abnormal angle creates resistance to ocular aqueous outflow
    • Results in increased intraocular pressure

Clinical Presentation

  • Ocular symptoms vary in severity – bilateral 70% of the time
  • Symptoms
    • Photophobia
    • Epiphora
    • Blepharospasm
    • Chronic red or irritated eyes, excessive tearing
    • Reduced visual acuity – eventual blindness
  • Signs
    • Globe enlargement/edema
    • Iris and pupillary abnormalities
    • Optic nerve cupping
    • Myopia
    • Corneal opacification
    • Elevated intraocular pressure
    • Thinning of anterior sclera, anomalous deep anterior chamber

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Glaucoma (Primary Congenital), CYP1B1 Sequencing 0051476
Method: Polymerase Chain Reaction/Sequencing

Diagnostic or carrier testing for primary congenital glaucoma and related disorders

Rare diagnostic errors may occur due to primer-site mutations

Large gene deletions/duplications and deep intronic mutations are not identified