Indications for Testing

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

Laboratory Testing

• CYP1B1 sequencing – absence of mutations does not necessarily rule out carrier status or the presence of disease

Differential Diagnosis

• Corneal edema or opacity
  • Ocular
    • Birth trauma
    • Sclerocornea
    • Keratitis
    • Peters anomaly
  • Systemic
    • Mucopolysaccharidoses
    • Cystinosis
    • Niemann-Pick disease
    • Familial dysautonomia
• Corneal enlargement
  • Axial myopia
  • Hereditary megalocornea
  • Keratoglobus
• Epiphora and red-eye
  • Conjunctivitis
  • Corneal abrasion
  • Uveitis
  • Keratitis
• Photophobia
  • Ocular
    • Keratitis
    • Aniridia
    • Iritis
    • Cataract
  • Systemic
    • Albinism
    • Meningitis
    • Posterior fossa tumor

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.

Epidemiology

• Incidence – 1/5-20,000 in U.S.; 1/2,500 in the Middle East; 1/1,250 in Slovakian gypsies
  • Accounts for 4% of childhood blindness
• Age – usually recognized by ≤2 years
• Sex – M>F, 3:1 in U.S.; M<F, 2:3 in Japan

Inheritance

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

Pathophysiology

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

Clinical Presentation

• Ocular symptoms vary in severity and are bilateral 70% of the time
• Symptoms
  • Photophobia
  • Epiphora
  • Blepharospasm
  • Chronic red or irritated eyes
  • Cloudy/poor vision
• Signs
  • Globe enlargement and edema
  • Iris and pupillary abnormalities
  • Optic nerve cupping
  • Myopia
  • Corneal opacification
  • Elevated intraocular pressure

Tests generally appear in the order most useful for common clinical situations

General

• Bejjani BA, Edward DP. Primary Congenital Glaucoma. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org [Last Updated: 3 Dec 2007; Accessed: 1 Jul 2009] 
• Ho CL, Walton DS. Management of childhood glaucoma. Curr Opin Ophthalmol. 2004; 15 (5) :460-464.PubMed
• Ho CL, Walton DS. Primary congenital glaucoma: 2004 update. J Pediatr Ophthalmol Strabismus. 2004; 41 (5) :271-288.PubMed
• Kirwan C, O'Keefe M. Paediatric aphakic glaucoma. Acta Ophthalmol Scand. 2006; 84 (6) :734-739.PubMed
• Lloyd IC, Ashworth J, Biswas S, Abadi RV. Advances in the management of congenital and infantile cataract. Eye. 2007; 21 (10) :1301-1309.PubMed
• Vasiliou V, Gonzalez FJ. Role of CYP1B1 in glaucoma. Annu Rev Pharmacol Toxicol. 2008; 48 :333-358.PubMed

Central Nervous System Tumors
Jewish Genetic Disease