Abstract
Purpose :
Pattern dystrophies represent a heterogeneous family of inherited diseases frequently caused by pathogenic PRPH2 variants. However, a number of other genetic and acquired conditions phenotypically mimic pattern dystrophy (PD). Distinguishing these conditions by clinical examination and imaging is challenging even for experienced ophthalmic genetics (OG) specialists, emphasizing the role of genetic testing and accurate history taking for these patients. The purpose of this study was to determine what proportion of patients with a clinical diagnosis of PD receive a confirmatory molecular genetic diagnosis, and to define the spectrum of alternate diagnoses ultimately identified for this patient cohort.
Methods :
A retrospective case review was performed for 80 consecutive patients initially diagnosed with PD at a single academic OG center within the last 15 years for whom electronic medical records were available. Genetic testing results were evaluated, as well as updated diagnoses and medication histories. Statistical analysis was performed by t-test.
Results :
Eighty patients (44 female, 36 male) received an initial clinical diagnosis of PD. The average age at presentation was 52.1 yr (range 18–79). Genetic testing was not completed or results were unavailable for 14 patients (7 female, 7 male), and the average age for this group (55.5 yr) was not statistically significantly different from that of the 66 patients (37 female, 29 male) who did have genetic testing (51.3 yr) (p = 0.32). Of the 66 patients with genetic test results, 27 (41%) had causative pathogenic PRPH2 variants consistent with a diagnosis of PD. In contrast, 39 individuals (59%) were found to have alternate genetic or acquired etiologies, or had inconclusive genetic tests; these included heterozygous IMPG2 variants (n=2), biallelic pathogenic ABCA4 variants (n=9), other genetic etiologies (n=4), or inconclusive testing (n=15). Non-genetic etiologies included autoimmune disease (n=1) or a history of pentosan polysulfate use (n=8). In total, a molecular diagnosis was identified for 41 of the 66 patients (62%) who underwent testing.
Conclusions :
Despite improved genetic testing technologies and clinical diagnostics, the clinical and molecular diagnosis of PD and its phenotypic mimickers remains challenging. Additional causative genes are likely yet to be discovered, and clinicians must also consider important acquired or rare genetic etiologies in the differential diagnosis.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.