Tuberous Sclerosis Complex: Genotype/Phenotype Correlation of Retinal Findings

被引:50
作者
Aronow, Mary E. [1 ]
Nakagawa, Jo Anne [2 ]
Gupta, Ajay [3 ]
Traboulsi, Elias I. [1 ]
Singh, Arun D. [1 ]
机构
[1] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA
[2] Tuberous Sclerosis Alliance, Silver Spring, MD USA
[3] Cleveland Clin, Dept Pediat Epilepsy, Neurol Inst, Cleveland, OH 44106 USA
关键词
MUTATIONAL ANALYSIS; TSC1; IDENTIFICATION; HAMARTOMAS; GENE;
D O I
10.1016/j.ophtha.2012.03.020
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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. Ophthalmology 2012; 119: 1917-1923 (C) 2012 by the American Academy of Ophthalmology.
引用
收藏
页码:1917 / 1923
页数:7
相关论文
共 24 条
  • [1] Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States
    An, Kit Sing
    Williams, Aimee T.
    Roach, E. Steve
    Batchelor, Lori
    Sparagana, Steven P.
    Delgado, Mauricio R.
    Wheless, James W.
    Baumgartner, James E.
    Roa, Benjamin B.
    Wilson, Carolyn M.
    Smith-Knuppel, Teresa K.
    Cheung, Min-Yuen C.
    Whittemore, Vicky H.
    King, Terri M.
    Northrup, Hope
    [J]. GENETICS IN MEDICINE, 2007, 9 (02) : 88 - 100
  • [2] Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B
    Catania, MG
    Mischel, PS
    Vinters, HV
    [J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2001, 60 (07) : 711 - 723
  • [3] Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs
    Dabora, SL
    Jozwiak, S
    Franz, DN
    Roberts, PS
    Nieto, A
    Chung, J
    Choy, YS
    Reeve, MP
    Thiele, E
    Egelhoff, JC
    Kasprzyk-Obara, J
    Domanska-Pakiela, D
    Kwiatkowski, DJ
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (01) : 64 - 80
  • [4] Eagle RC, 2000, ARCH OPHTHALMOL-CHIC, V118, P711
  • [5] History of the tuberous sclerosis complex
    Gomez, MR
    [J]. BRAIN & DEVELOPMENT, 1995, 17 : 55 - 57
  • [6] Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis
    Jones, AC
    Daniells, CE
    Snell, RG
    Tachataki, M
    Idziaszczyk, SA
    Krawczak, M
    Sampson, JR
    Cheadle, JP
    [J]. HUMAN MOLECULAR GENETICS, 1997, 6 (12) : 2155 - 2161
  • [7] Comprehensive mutation analysis of TSC1 and TSC2 -: and phenotypic correlations in 150 families with tuberous sclerosis
    Jones, AC
    Shyamsundar, MM
    Thomas, MW
    Maynard, J
    Idziaszczyk, S
    Tomkins, S
    Sampson, JR
    Cheadle, JP
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (05) : 1305 - 1315
  • [8] HIGH-INCIDENCE OF FUNDUS HAMARTOMAS AND CLINICAL-SIGNIFICANCE OF A FUNDUS SCORE IN TUBEROUS SCLEROSIS
    KIRIBUCHI, K
    UCHIDA, Y
    FUKUYAMA, Y
    MARUYAMA, H
    [J]. BRAIN & DEVELOPMENT, 1986, 8 (05) : 509 - 517
  • [9] TUBEROUS SCLEROSIS
    KWIATKOWSKI, DJ
    SHORT, MP
    [J]. ARCHIVES OF DERMATOLOGY, 1994, 130 (03) : 348 - 354
  • [10] Mullaney PB, 1997, J PEDIAT OPHTH STRAB, V34, P372