Abstract
Purpose:
To determine the concordance of clinical and molecular genetic testing in patients from a clinic specializing in the evaluation and management of retinal dystrophies.
Methods:
A two-year retrospective analysis was conducted on data from patients who attended a monthly retinal dystrophy clinic at the Cleveland Clinic Cole Eye Institute. The initial clinical diagnosis and the eventual molecular genetic test result from one of several CLIA-approved laboratories were recorded and reviewed.
Results:
120 patients agreed to undergo genetic testing in addition to a complete clinical work-up that included a clinical examination and a combination of one or more of the following: fundus photography, optical coherence tomography, fundus autofluorescence imaging and electroretinography. The three most common clinical diagnoses were Stargardt disease (STGD, 32 patients), retinitis pigmentosa (RP, 29 patients) and Leber congenital amaurosis (LCA, 24 patients). A molecular diagnosis was reached in 76 patients (63.33%). Patients with RP had the lowest mutation detection rate. We also found as reported by others that some patients with seemingly isolated RP had mutations in Usher syndrome genes or Bardet-Biedl syndrome genes. 10 (31.25%) patients with a clinical diagnosis of Stargardt disease were not found to have one or more mutations in ABCA4. 5 (20.85%) of patients with a clinical diagnosis of LCA had in fact other conditions such as blue cone monochromacy or Alström disease.
Conclusions:
With currently available commercial genetic testing methodology, and in the context of a clinic that specializes in the evaluation of retinal dystrophies, at least two-thirds of patients will receive a molecular genetic test result that confirms the clinical one. While patients with retinitis pigmentosa continue to have a lower yield of causal gene identification, others are misdiagnosed with LCA when in fact they have Alström disease or blue-cone monochromacy.
Keywords: 696 retinal degenerations: hereditary •
539 genetics •
467 clinical laboratory testing