Clinical Guidance

Genotype-phenotype correlations in autosomal recessive RPE65-related retinal degeneration do not allow reliable prediction of disease severity in an individual ; however, certain variant classes have been associated with milder or more severe phenotypes. The severe early-onset phenotypes (LCA and EOSRD) are more often associated with null variants (e.g., nonsense, frameshift, canonical splice). RPE65-related EOSRD. Compared to LCA, EOSRD reflects partial retention of isomerohydrolase activity and is generally associated with biallelic missense or hypomorphic variants that allow some residual RPE65 function.

Diagnostic Criteria

No consensus clinical diagnostic criteria for autosomal recessive RPE65-related retinal degeneration have been published.

Suggestive Findings

Autosomal recessive RPE65-related retinal degeneration should be suspected in individuals with the following clinical, electroretinographic, and imaging findings and family history.

Clinical findings

Source: GeneReviews — "Autosomal Recessive RPE65-Related Retinal Degeneration"

Management Guidelines

No clinical practice guidelines for autosomal recessive RPE65-related retinal degeneration have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of individuals diagnosed with autosomal recessive RPE65-related retinal degeneration, the evaluations included (if not performed as part of the evaluation that led to the diagnosis) are recommended, and their purpose summarized. Note that some evaluations may be indicated only in individuals considering subretinal gene supplementation therapy .

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Note: No consensus surveillance guidelines exist; the intervals shown are based on expert opinion and clinical practice. Table 5. Autosomal Recessive RPE65-Related Retinal Degeneration: Recommended Surveillance