CLINICAL-FEATURES AND LINKAGE ANALYSIS OF A FAMILY WITH AUTOSOMAL DOMINANT JUVENILE GLAUCOMA

Background: Juvenile glaucoma is an uncommon form of open-angle glauco ma that is usually recognized during childhood or early adulthood and which often has a strong family history. Methods: The authors clinical ly characterized a large multigeneration family with autosomal-dominan t, juvenile-onset, open-angle glaucoma. Linkage analysis with short ta ndem repeat polymorphisms was used to evaluate the Rieger's syndrome l ocus as the site of the disease-causing mutation. Results: Forty membe rs of a family with a five-generation history of open-angle glaucoma w ere examined. Clinical data were available from an additional five ind ividuals, three of whom were deceased. Older family members provided l imited information about the visual history of five other deceased ind ividuals 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 affec ted patients had an affected parent. The average age at diagnosis was 18 years (range, 8-30 years). Affected family members tended to be myo pic but lacked other ocular or systemic abnormalities. The intraocular pressures (IOPs) of affected individuals were commonly more than 50 m mHg when they were first examined. Gonioscopy showed the angles to be open, with no abnormal pigmentation, iris processes, or embryonic tiss ue. Topical medications were initially effective in controlling IOP, b ut surgery was usually required for long-term pressure control. The Ri eger's syndrome locus on chromosome 4q25 was excluded as the site of t he 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 ide ntify the chromosomal location of a glaucoma-causing gene. This gene i s genetically distinct from the chromosome 4 locus that was recently a ssociated with Rieger's syndrome.