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Background Facial angiofibroma is the most predominant cutaneous manifestation of tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder impacting the mechanistic target of rapamycin (mTOR). Facial angiofibroma can bleed spontaneously, impair eyesight, and cause aesthetic disfiguration causing psychological and social stress. To date, there is little or no evidence on the demographics, and other TSC features associated with facial angiofibroma or the use of mTOR inhibitor for the management of facial angiofibroma. This is a retrospective study of TSC Alliance’s Natural History Database aimed to characterize facial angiofibroma and to evaluate features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors for the management of facial angiofibroma. Data in the NHD was obtained from 18 clinical sites in the US since 2006. Results Of the 2240 patients, 2088 patients were enrolled in the US and data from 2057 patients were included in this analysis. The mean (median) age of overall TSC patients was 22.4 (19.0) years. A total of 69 patients were ≤ 5 years of age. Facial angiofibroma was noted in 1329 (64.6%) patients with TSC. Patients with facial angiofibroma were older on average (Mean: 25.9 [median, 23.0] vs. 16.0 [12.4 years] years, p TSC2 mutation (38.9% vs. 34.8%) was more common than TSC1 mutation (12.3% vs. 18.1%), and the incidence rate of most of the other TSC-related manifestations was significantly higher in patients with facial angiofibroma. Majority of patients had focal seizures (72.8% vs. 60.7%), followed by angiomyolipoma (63.7% vs. 21.8%) and renal cysts (59.4% vs. 33.5%). The age groups, 11–17 (odds ratio [OR], 2.53) and 18–45 years (5.98), TSC2 mutation (1.31), focal seizures (1.50), ADHD (1.47) angiomyolipoma (2.79), and renal cysts (2.63) were significantly associated with a higher risk of facial angiofibroma based on multivariate logistic regression. Abrasive or laser therapy was used by 17.1% and 2.6% patients, respectively. Topical mTOR inhibitor use was noted for 329 (24.8%) patients with facial angiofibroma. Overall systemic mTOR inhibitor use was observed in 399 (30.0%) patients for management of one or more TSC manifestations. Use of systemic mTOR inhibitor for facial angiofibroma was noted for 163 (12.3%) patients, among whom only 9 (0.7%) patients used exclusively for the management of facial angiofibroma. Of the patients with facial angiofibroma, 44.6% did not receive any treatment. Significantly higher use of topical mTOR inhibitor was associated with the 11–17 years age group (OR, 1.67), anxiety (1.57), angiomyolipoma (1.51), and renal cysts (1.33). Conclusions The presence of TSC2 mutations and most other TSC-related manifestations was significantly higher in patients with facial angiofibroma. About one-fourth of patients with facial angiofibroma used a topical mTOR inhibitor and use of systemic mTOR inhibitor for the management of facial angiofibroma or for the other manifestations was noted for 30.0%. About 44.6% of patients did not receive any treatment for the management of facial angiofibroma.

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.

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.

Objective To evaluate the impact of pediatric sleep disturbances and night-time seizure monitoring of children with rare epilepsy syndromes on the sleep quality and mental health of caregivers. Study design A cross-sectional study was conducted using caregiver entered data from the Rare Epilepsy Network on pediatric sleep disturbances and Patient Reported Outcomes Measurement Information System measures for caregiver fatigue, sleep disturbance, sleep-related impairment, depression, anxiety, companionship, and cognition. Logistic regression was used to examine associations between risk factors and caregiver sleep quality. Results Non-Hispanic white mothers comprised 83% of the 742 respondents in this study. After adjusting for covariates, difficulty falling asleep, excessive daytime sleepiness, frequent night-time awakenings, and very restless sleep in children were associated with fatigue (aOR 95% CI, 1.5-2.2), sleep-related disturbance (aOR 95% CI, 1.7-2.6) and sleep impairment (aOR 95% CI, 1.5-2.4) in caregivers. Caregiver anxiety (aOR 95% CI, 3.6-6.0) and depression (aOR 95% CI, 2.8-6.0) were also highly associated with their fatigue and sleep quality, whereas companionship (aOR 95% CI, 0.3-0.4) and higher caregiver cognition (aOR 95% CI, 0.1-0.2) were protective. In addition, sharing a room or bed or using methods that require listening for seizures were significantly related to sleep disturbance and fatigue in the caregivers. Conclusions In rare epilepsies, pediatric sleep disturbances and night-time seizure monitoring are significantly associated with caregiver fatigue and poor sleep quality. In addition to the intense caregiving needs of children with rare epilepsies, fatigue and poor sleep quality in caregivers may contribute to or result from mental health problems.

Alterations in cerebral transvascular pressure, associated with dehydration or hyperosmolality, have been implicated as contributing factors in ICH of LBW infants. If correct, fluid restriction of LBW infants (