Abstract
Purpose :
To determine the occurrence rate of open angle glaucoma (OAG) in patients with fibrillin1 (FBN1) mutations with a confirmed clinical diagnosis of the Marfan syndrome (MFS). This is a retrospective clinical and molecular analysis using Whole Genome Sequencing (WGS)
Methods :
The All of Us database (V7) was used for analysis of prevalence of OAG in patients with a clinical diagnosis of MFS and a FBN1 mutation. The database includes 413,000 controlled and curated participants among whom 169 or 1:2,500 carry a clinical diagnosis of the MFS; 245,388 participants underwent WGS and 169, or 1:2,100, have a confirmed pathogenic or likely pathogenic FBN1 mutation. The total number of OAG patients was 19,130 of whom 3,600 had completed WGS; 27 had the MFS syndrome. The distribution of age of onset in MFS patients was compared to a control population
Results :
The prevalence of self-reported MFS was 1:2,500; when using curated clinical data and DNA analysis for pathogenic and presumed pathogenic FBN1 variants, the prevalence increased to 1:2,100.
OAG was self-reported in 19,130 participants; 3,600 participants underwent WGS. The cooccurrence of OAG and MFS was recorded in 27 patients; on WGS sixteen participants or 13.7% had OAG and MFS. Age of onset was concentrated in patients above age 40 years
Conclusions :
A high frequency of OAG is found in the MFS, using V7 of the All of Us database. The pathogenesis of open angle glaucoma in the Marfan syndrome remains unknown, but expression of FBN1 is high in the trabecular meshwork and in the cribriform plate. Patients with the Marfan syndrome ought to undergo lifelong annual ophthalmological examinations and detection and treatment of OAG should be included in the diagnostic priorities
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.