title: Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings.
abstract: 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).
  
  
  METHODS
  Retrospective consecutive case series.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Aronow
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Nakagawa
authors.forename: Ajay
authors.initials: A
authors.lastname: Gupta
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Arun D
authors.initials: AD
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D018207:Angiomyolipoma / Q000235:genetics / Q000473:pathology; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000235:genetics / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000175:diagnosis* / Q000235:genetics*; D012189:Retrospective Studies; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins