Highly Variable Disease Courses in Siblings with Stargardt Disease

Area of Science:

• Ophthalmology
• Genetics
• Retinal Diseases

Background:

• Stargardt disease (STGD1) is an inherited retinal dystrophy.
• Understanding intersibling phenotypic concordance is crucial for predicting disease course.

Purpose of the Study:

• To investigate the concordance of clinical phenotypes between siblings diagnosed with Stargardt disease (STGD1).

Main Methods:

• Retrospective cohort study of siblings with genetically confirmed STGD1.
• Comparison of age at onset, best-corrected visual acuity (BCVA), time to severe visual impairment, and retinal atrophy area.
• Qualitative assessment of fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) images.

Main Results:

• Significant differences in age at onset (13-39 years) and time to severe visual impairment (1-29 years) were observed in several families.
• Disease duration-matched BCVA showed notable differences between siblings.
• Central retinal atrophy area and FAF/SD-OCT phenotypes were highly comparable between siblings.

Conclusions:

• Phenotypic discordance is prevalent in STGD1 siblings, even with identical ABCA4 variants.
• Functional outcomes like BCVA and disease progression vary substantially despite similar FAF phenotypes.
• This discordance complicates genotype-phenotype correlations and necessitates individualized patient management strategies.