TY - JOUR
T1 - Tuberous sclerosis complex
T2 - Genotype/phenotype correlation of retinal findings
AU - Aronow, Mary E.
AU - Nakagawa, Jo Anne
AU - Gupta, Ajay
AU - Traboulsi, Elias I.
AU - Singh, Arun D.
N1 - Funding Information:
To meet the inclusion criteria for this study, patients were required to have definite TSC based on the 1998 Tuberous Sclerosis Complex Consensus Conference revised diagnostic criteria 10 or a known TSC disease-causing mutation in the setting of limited clinical findings. Between 2000 and 2009, patients were consecutively enrolled in the Cleveland Clinic Foundation Tuberous Sclerosis Complex Program (CCF-TSCP), a multidisciplinary pediatric and adult program coordinated by the Pediatric Epilepsy Department. As part of their participation in this clinical program, patients were evaluated by multiple subspecialty teams and underwent a standard series of radiographic imaging tests for systemic evaluation. Data regarding patient gender, age of diagnosis of TSC, whether or not genetic testing was performed, presence of a mutation in the TSC1 or TSC2 genes, age at time of ophthalmic examination, detailed retinal findings, presence of systemic disease manifestations (i.e., the presence of major diagnostic criteria), and whether or not there was a diagnosis of epilepsy or cognitive impairment were analyzed retrospectively. This research was approved by the institutional review board of the Cleveland Clinic Foundation. A second, larger cohort of patients with TSC was enrolled in the Tuberous Sclerosis Alliance (TSC-A), a national multicenter TSC natural history database affiliated with 16 TSC clinical centers across the United States, including the Cleveland Clinic TSC Program. It is important to note that a subset of individuals enrolled in the TSC-A database were Cleveland Clinic Foundation patients. Thus, for this study, these individuals were excluded from the TSC-A population because they had been separately analyzed as part of the CCF-TSCP group. A search of the TSC-A national multicenter TSC natural history database identified individuals who had undergone complete ophthalmic examination. Permission to access the TSC-A database was granted through a collective and individual institutional review board approval.
PY - 2012/9
Y1 - 2012/9
N2 - Objective: To evaluate genotype/phenotype correlations in individuals with astrocytic hamartoma (AH) and retinal achromic patch (AP) in the setting of tuberous sclerosis complex (TSC). Design: Retrospective consecutive case series. Participants: A total of 132 patients enrolled in the Cleveland Clinic Foundation Tuberous Sclerosis Program (CCF-TSCP) and 907 patients from the Tuberous Sclerosis Alliance (TSC-A). Methods: Patient gender, age at TSC diagnosis, presence of TSC1 or TSC2 mutations, detailed ophthalmic examination findings, systemic manifestations, and whether or not the patient had a diagnosis of epilepsy or cognitive impairment were analyzed. Main Outcome Measures: Genotype/phenotype correlation of retinal findings and systemic disease manifestations. Results: No significant difference was found in the prevalence of AH or AP in the CCF-TSCP (36.1%) and TSC-A (34.1%) groups (P = 0.743). Astrocytic hamartomas were bilateral in 43.3% and 18.1% (P = 0.009) and multiple in 40.0% and 15.3% (P = 0.008) in the CCF-TSCP and TSC-A groups, respectively. In the CCF-TSCP group, the average number of AH was 4 (range, 2-7). Average tumor size was 1.0 disc diameter (range, 0.5-2.5 disc diameters). The most common location was along the arcades (41.5%), adjacent to the optic nerve (29.2%), and in the retinal periphery (27.7%). In the CCF-TSCP group, AP was observed in 12.0% of patients (40.0% bilateral, 50.0% multiple). The presence of retinal features was associated with giant cell astrocytoma (37.1% vs. 14.6%; P = 0.018), renal angiomyolipoma (60.0% vs. 27.1%; P = 0.003), cognitive impairment (77.1% vs. 43.8%; P = 0.002), and epilepsy (91.4% vs. 70.8% (P = 0.022) in those with and without retinal findings, respectively. In patients with retinal findings in both the CCF-TSCP and TSC-A groups, mutations in TSC2 were more frequent than in TSC1, 3.3 times and 5.8 times, respectively; in those without retinal findings, the relative rates were 0.67 times and 2.3 times, respectively. Conclusions: Individuals with retinal findings are more likely to have concomitant subependymal giant cell astrocytomas, renal angiomyolipomas, cognitive impairment, and epilepsy. TSC2 mutations are more frequent in patients with retinal findings than in those without retinal findings. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
AB - Objective: To evaluate genotype/phenotype correlations in individuals with astrocytic hamartoma (AH) and retinal achromic patch (AP) in the setting of tuberous sclerosis complex (TSC). Design: Retrospective consecutive case series. Participants: A total of 132 patients enrolled in the Cleveland Clinic Foundation Tuberous Sclerosis Program (CCF-TSCP) and 907 patients from the Tuberous Sclerosis Alliance (TSC-A). Methods: Patient gender, age at TSC diagnosis, presence of TSC1 or TSC2 mutations, detailed ophthalmic examination findings, systemic manifestations, and whether or not the patient had a diagnosis of epilepsy or cognitive impairment were analyzed. Main Outcome Measures: Genotype/phenotype correlation of retinal findings and systemic disease manifestations. Results: No significant difference was found in the prevalence of AH or AP in the CCF-TSCP (36.1%) and TSC-A (34.1%) groups (P = 0.743). Astrocytic hamartomas were bilateral in 43.3% and 18.1% (P = 0.009) and multiple in 40.0% and 15.3% (P = 0.008) in the CCF-TSCP and TSC-A groups, respectively. In the CCF-TSCP group, the average number of AH was 4 (range, 2-7). Average tumor size was 1.0 disc diameter (range, 0.5-2.5 disc diameters). The most common location was along the arcades (41.5%), adjacent to the optic nerve (29.2%), and in the retinal periphery (27.7%). In the CCF-TSCP group, AP was observed in 12.0% of patients (40.0% bilateral, 50.0% multiple). The presence of retinal features was associated with giant cell astrocytoma (37.1% vs. 14.6%; P = 0.018), renal angiomyolipoma (60.0% vs. 27.1%; P = 0.003), cognitive impairment (77.1% vs. 43.8%; P = 0.002), and epilepsy (91.4% vs. 70.8% (P = 0.022) in those with and without retinal findings, respectively. In patients with retinal findings in both the CCF-TSCP and TSC-A groups, mutations in TSC2 were more frequent than in TSC1, 3.3 times and 5.8 times, respectively; in those without retinal findings, the relative rates were 0.67 times and 2.3 times, respectively. Conclusions: Individuals with retinal findings are more likely to have concomitant subependymal giant cell astrocytomas, renal angiomyolipomas, cognitive impairment, and epilepsy. TSC2 mutations are more frequent in patients with retinal findings than in those without retinal findings. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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U2 - 10.1016/j.ophtha.2012.03.020
DO - 10.1016/j.ophtha.2012.03.020
M3 - Article
C2 - 22608477
AN - SCOPUS:84865679581
SN - 0161-6420
VL - 119
SP - 1917
EP - 1923
JO - Ophthalmology
JF - Ophthalmology
IS - 9
ER -