Burden of renal angiomyolipomas associated with tuberous sclerosis complex: results of a patient and caregiver survey.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors in multiple organs, including non-cancerous kidney lesions known as renal angiomyolipomas. This study's objective is to describe the age-stratified morbidity, treatment patterns, and health-related quality of life of TSC patients with renal angiomyolipomas in the United States. A cross-sectional, anonymous web-based survey was conducted with a convenience sample of TSC patients and caregivers identified through a patient advocacy organization. RESULTS: Out of the total sample of 676, 182 respondents reported having kidney complications with 33% of the pediatric group and 25% of the adult group with TSC reporting them. Of those with kidney complications, 110 (60%) reported a diagnosis of renal angiomyolipomas, of which 79 (72%) were adult patients and 31 (28%) were pediatric age patients. Eighty-four percent of the pediatric group and 76% of the adult group reported lesions on both kidneys. Of the patients experiencing involvement of only one kidney, 60% of the pediatric group and 21% of the adult group reported having multiple tumors within the affected kidney. Almost all of the sample (99%) reported seeing a physician and having a procedure or test for TSC in the past year. Less than half the respondents (44%) reported being hospitalized in the past year. Thirty-nine percent reported an emergency room visit as well. Compared to scores for patients with kidney disease, the angiomyolipoma adult patients reported significantly lower Mental Component Summary scores on the SF-12. CONCLUSIONS: Renal angiomyolipomas burden leads to frequent healthcare resource use including hospitalization, invasive treatments, and surgical procedures, which result in an impaired mental health related quality of life.

Economic burden, work, and school productivity in individuals with tuberous sclerosis and their families.

AIMS: Tuberous sclerosis complex (TSC) is a multi-organ autosomal-dominant, genetic disorder with incomplete penetrance. The multiple manifestations of TSC and impacts to numerous organ systems represent significant disease, healthcare, and treatment burden. The economic and employment burden of the disease on individuals and their families is poorly understood. This study assessed the cost of illness and work and school productivity burden associated with TSC in a cross-sectional web-survey sample. MATERIALS AND METHODS: Eligible TSC individuals and caregivers were invited through the Tuberous Sclerosis Alliance advocacy group to complete a web-based survey about illness characteristics, treatment, disease burden, direct and indirect healthcare costs, work and school impairment. RESULTS: Data from 609 TSC adults or caregiver respondents with no cognitive impairments were analyzed. TSC adults (>18 years of age) had significantly higher direct out-of-pocket costs for ER visits, expenses for medical tests and procedures, alternative treatments, medications and lifetime cost of surgeries compared to TSC pediatric individuals. Both TSC adults and TSC caregivers reported work and school absenteeism and presenteeism; however, adults reported significantly higher absenteeism and presenteeism and overall activity impairment due to TSC, as might be expected, compared to TSC caregivers. TSC adults had significantly higher absenteeism and presenteeism rates compared to adults with moderate-to-severe plaque psoriasis and muscular sclerosis. CONCLUSIONS: TSC results in considerable direct out-of-pocket medical costs and impairment to work productivity, especially for adults. Future studies should include the comparator group and examine direct cost burden in the US using electronic medical records and insurance databases.

Predictors of Drug-Resistant Epilepsy in Tuberous Sclerosis Complex.

Utilizing the multicenter TSC (tuberous sclerosis complex) Natural History Database including 2034 subjects, this study aimed to identify predictors of drug-resistant epilepsy in TSC. Basic epilepsy data were available for 1965 individuals in the database. Supplemental data were further collected from 1546 of these subjects through directed site queries, addressing additional epilepsy characteristics including the presence of drug-resistant epilepsy, therapies trialed, and outcomes of specific therapies. Epilepsy was reported in 86.4% of individuals with TSC. Infantile spasms were reported in 45.2% of individuals and focal seizures were reported in 84.4% of individuals. In those with focal epilepsy, drug resistance was reported in 59.6%, with focal seizure onset prior to age 1 year (odds ratio [OR] 1.9, confidence interval [CI] 1.4-2.5, P < .001), infantile spasms (OR 2.0, CI 1.5-2.5, P < 0.001), and infantile spasms incompletely responsive to therapy (OR 47.6, CI 6.7-333.3, P < 0.001) being associated with an increased likelihood of drug resistance.

Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings.

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.