Abstract
Purpose :
To define characteristic ocular features in a group of patients with autosomal recessive (AR) PROM1 cone-rod dystrophy (CRD).
Methods :
Four patients from three families, one with a single affected male, a second with two affected brothers, and a third with a single affected female, were diagnosed with CRD when first seen at the ages of 22, 15, 21 and 21 years, respectively. Clinical testing available for review included full-field electroretinogram (ERG) in three patients, as well as infrared autofluorescence (IRAF), spectral domain optical coherence tomography (SD-OCT), and color fundus photography in all four patients. Whole exome sequencing (WES) was performed on all cases, and whole genome sequencing (WGS) was performed in two families.
Results :
Initial WES found compound heterozygous variants of the PROM1 gene in the male case in the first family, but only found single heterozygous disease-associated variants in the other two families. WGS uncovered a large, 2 exon deletion of PROM1 in the two brothers and a deleterious intronic variant in the female patient. Two patients reported symptoms beginning in the first decade, while the two brothers reported symptoms in the second decade of life. ERG showed markedly reduced cone-isolated amplitudes and variably reduced rod-isolated amplitudes. The dark-adapted combined rod and cone responses demonstrated notably reduced a-wave amplitudes and moderately reduced b-waves, and the resultant waveform resembled that of the normal rod-isolated response. On fundus exam, oval-shaped macular lesions of varying severity were observed in each patient. Each patient showed several small, circular hypo-autofluorescent lesions within the macular region on IRAF. On macular SD-OCT, residual ELM and EZ bands were observed in the foveolas of three patients. In addition to their macular lesions, three patients showed extramacular circular atrophic lesions of various sizes, often with hyperpigmentary changes.
Conclusions :
While none of the findings in this study were likely pathognomonic, the autofluorescence changes, and the peripheral retinal and ERG findings reported in these four AR PROM1-associated CRD patients became a recognizable phenotype in this cohort of patients. Similar findings may be observed in CRD due to CDHR1, a functionally related gene. Our findings may help to focus genetic screening in patients with these findings.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.