Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings

Area of Science:

• Ophthalmology
• Genetics
• Neurology

Background:

• Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the growth of hamartomas in multiple organs.
• Retinal astrocytic hamartomas (AH) and achromic patches (AP) are ocular manifestations of TSC.
• Understanding genotype/phenotype correlations is crucial for managing TSC patients.

Purpose of the Study:

• To investigate the relationship between retinal findings (AH and AP) and systemic disease manifestations in TSC.
• To evaluate the correlation between specific gene mutations (TSC1/TSC2) and the presence of retinal lesions in TSC patients.

Main Methods:

• A retrospective analysis of 132 patients from the Cleveland Clinic Foundation Tuberous Sclerosis Program (CCF-TSCP) and 907 patients from the Tuberous Sclerosis Alliance (TSC-A).
• Data collected included patient demographics, TSC diagnosis age, TSC1/TSC2 mutation status, ophthalmic findings, and systemic manifestations (epilepsy, cognitive impairment).
• Genotype/phenotype correlations of retinal findings and systemic disease were analyzed.

Main Results:

• No significant difference in AH or AP prevalence was observed between the CCF-TSCP and TSC-A groups.
• Retinal findings were associated with a higher incidence of subependymal giant cell astrocytomas, renal angiomyolipomas, cognitive impairment, and epilepsy.
• TSC2 mutations were more frequent in patients with retinal findings compared to those without.

Conclusions:

• Retinal manifestations in TSC are linked to increased risks of specific systemic complications, including brain tumors, kidney angiomyolipomas, cognitive impairment, and epilepsy.
• The frequency of TSC2 mutations is higher in TSC patients presenting with retinal lesions, suggesting a potential genotype-specific phenotype.