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Mark P McGarrey, Sandip Patel, Mary E Aronow, Elizabeth A. Thiele; Ophthalmic and Genetic Findings in a Large Cohort of Patients with Tuberous Sclerosis Complex. Invest. Ophthalmol. Vis. Sci. 2020;61(7):5176.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate ophthalmic features and genetic findings in large cohort of patients with tuberous sclerosis complex (TSC).
The Herscot Center for Tuberous Sclerosis Complex at the Massachusetts General Hospital provides comprehensive multi-disciplinary care for over 400 families from around the world. In this retrospective chart review, we analyzed ophthalmic manifestations and genetic mutations in individuals with TSC.
From 160 medical records, 139 (86.7%) included detailed eye examination findings. Ophthalmic features of TSC, including retinal astrocytic hamartoma (AH) and/or retinal achromic patch (AP), were present in 49 individuals (35.3%). Only 2 (1.4%) required treatment of the AH due to visually significant exudation (Both cases demonstrated response to oral rapamycin. One case required additional photodynamic therapy and intravitreal steroids). Of 139 individuals, 114 (82.0%) underwent genetic testing. Mutational testing was conclusive in 100 cases (87.7%). Mutations in TSC2 were more common than in TSC1 and were detected in 34 of 41 patients (82.9%) with ocular findings versus 40 of 73 patients (54.8%) without ocular findings (p=0.001). In individuals with ocular manifestations, the specific mutation was available in 27 cases (65.9%). Splice site mutations (33.3%) predominated, followed by missense (25.9%), frameshift (18.5%), deletion (14.8%), duplication (3.7%), and nonsense (3.7%) mutations. A novel finding was that 5 individuals (3.6%) had juvenile cataract (for comparison, juvenile cataract affects 1 in 250 in the general population). In all 5 cases, a mutation in TSC2 was detected. Five specific mutations were identified among 3 of these individuals. Three of the mutations (60.0%) were missense variants and included mutations in MECP2 and SPTAN1. The MECP2 mutation, c.802 C>T (p.Arg268Trp), is a missense change that has previously been reported in Rett syndrome. The SPTAN1 mutation, c.5648 A>G (p.Asn1883Ser), is a missense mutation not previously reported as a disease-causing mutation.
Ocular manifestations including AH and AP occur in approximately one-third of individuals with TSC and rarely require treatment. Individuals with TSC2 mutations are more likely to have ophthalmic findings. The relatively large number of juvenile cataracts observed in this series suggests that this could be an under-recognized clinical feature of TSC.
This is a 2020 ARVO Annual Meeting abstract.
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