Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma

Abstract

Background: Juvenile glaucoma is an uncommon form of open-angle glaucoma that is usually recognized during childhood or early adulthood and which often has a strong family history.

Methods: The authors clinically characterized a large multigeneration family with autosomal-dominant, juvenile-onset, open-angle glaucoma. Linkage analysis with short tandem repeat polymorphisms was used to evaluate the Rieger's syndrome locus as the site of the disease-causing mutation.

Results: Forty members of a family with a five-generation history of open-angle glaucoma were examined. Clinical data were available from an additional five individuals, three of whom were decreased. Older family members provided limited information about the visual history of five other deceased individuals in the first three generations. Fifty-nine people were at 50% risk of harboring the disease-causing mutation; and of these, 30 were affected with glaucoma by examination or by family history. All affected patients had an affected parent. The average age at diagnosis was 18 years (range, 8-30 years). Affected family members tended to be myopic but lacked other ocular or systemic abnormalities. The intraocular pressures (IOPs) of affected individuals were commonly more than 50 mmHg when they were first examined. Gonioscopy showed the angles to be open, with no abnormal pigmentation, iris processes, or embryonic tissue. Topical medications were initially effective in controlling IOP, but surgery was usually required for long-term pressure control. The Rieger's syndrome locus on chromosome 4q25 was excluded as the site of the disease-causing mutation.

Conclusion: Juvenile open-angle glaucoma can occur as an autosomal dominant trait with high penetrance. Genetic linkage analysis of the family reported here has the potential to identify the chromosomal location of a glaucoma-causing gene. This gene is genetically distinct from the chromosome 4 locus that was recently associated with Rieger's syndrome.