OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes:CYP1B1

P4501B1

GLC3

Glaucoma
Cloudy cornea
Photophobia
Buphthalmos

Congenital Glaucoma

Clinical Characteristics

General description (for patients):

Glaucoma present at birth or in the first two years of life is generally called congenital glaucoma. It is often manifest as irritability, cloudy corneas, sensitivity to light, and profuse tearing.  In the chronic condition the corneas may be enlarged.  No other disease symptoms in the body are found in most cases of primary congenital glaucoma.  Delayed or inadequate treatment carries a serious risk of blindness.

Medical description:  

Infantile and childhood glaucoma can occur as an isolated (primary) disease or secondary to other malformations and disorders.  The primary disease may be manifest at birth as buphthalmos (enlarged corneas), photophobia, epiphora, and cloudy corneas with variable amounts of glaucomatous cupping.  Intraocular pressures in millimeters of mercury (mmHg) range from the low 20s to the 40s but usually near the lower extreme (normal 15-22 mmHg).  No anatomic defect has been found for what seems to be a disorder of the aqueous humor outflow mechanism.

Genetics:

Two loci have been linked to congenital glaucoma.  Only a few families have been found to link to the 1p36.2-1p36.1 locus.  Many more patients have mutations in the CYP1B1 or P4501B1 gene located on chromosome two (2p22-p21).  A pedigree of congenital glaucoma in the Amish of Southwestern Ontario has been reported to have two mutations linked to this condition.  One mutation involves a small deletion (1410del13) and the other a missense mutation (1505G>A) in CYP1B1.  Among six individuals with congenital glaucoma, four were compound heterozygotes and two were homozygous for the 13 bp deletion, consistent with autosomal recessive inheritance.

Treatment: 

Topical pressure-lowering medications and surgery can be effective.  Often some combination of the two is required.  It is important to remember that this is a bilateral disease in spite of frequent asymmetrical presentation. Lifelong monitoring is required.

Prognosis:

Visual outcome is variable depending somewhat upon age of diagnosis and patient compliance.  Other unknown factors play a role since even optimum care and treatment does not always prevent blindness.

Ancillary treatments and support:

None unless severe vision loss occurs, in which case mobility training, visual aids, and vocational rehabilitation can be helpful.

Specialists and specialty centers:

Ophthalmologist.

References:

Martin, S.N., Sutherland, J., Levin, A.V., Klose, R., Priston, M., and Heon, E.:  Molecular characterization of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness.  J. Med. Genet. 37: 422-427, 2000.  PubMed ID: 10851252

Stoilov, I., Akarsu, A.N., and Sarfarazi, M.:  Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21.  Hum. Molec. Genet. 6: 641-647, 1997.  PubMed ID: 9097971

Resources:

Congenital Glaucoma
Glaucoma Research Foundation
Fight for Sight