A population-based study to estimate survival and standardized mortality of tuberous sclerosis complex (TSC) in Taiwan

Jui-Hui Peng,Hung-Pin Tu,Chien-Hui Hong

doi:10.1186/s13023-021-01974-3

Abstract

BackgroundTuberous sclerosis complex (TSC) is an autosomal dominant disease with systemic manifestations, which can cause significant mortality and morbidity. Population-based epidemiological studies on TSC mortality and survival remain scarce, though several recent studies provide evidence that TSC survival rates are high and disease prognosis is fair for most patients. This study aims to estimate the life expectancy and mortality statistics in Taiwanese TSC patients, investigate prognosis and associations of TSC mortality based on demographic variables, and compare these results to past literature, especially for Asian patients.MethodsTaiwanese National Health Insurance (NHI) insurees can obtain Catastrophic Illness Certificates (CIC) for certain eligible diseases to waive copayments after diagnosis by two independent physicians. CIC holders for TSC during 1997–2010 were identified from the NHI Research Database. Queries on enrollment (CIC acquisition) age, endpoint (end of query period or death) age, sex, and comorbidities were obtained. Patients were separated into cohorts (endpoint age, sex, and age of diagnosis), and analyzed accordingly.Results471 patients (232 male, 239 female) were identified, of which 14 died. Compared to literature, patients showed similar demographics (age range, diagnosis age, sex distribution); similar manifestations and prevalence (epilepsy, intellectual disability, renal disease); lower disease prevalence (1 in 63,290); lower mortality (0.21% per year); and near-identical standardized mortality ratio (4.99). A cumulative mortality of 4.08% was found over 14 years, though mortality plateaued at 7 years post-enrollment, suggesting a good overall survival rate; comparable with previous studies in Asian patients. Enrollment age was a significant prognostic factor, with late-enrollment (age > 18) patients at higher risk for all-cause mortality (Hazard ratio = 6.54). Average remaining lifetime was significantly lower than the general population, and decreased with age.ConclusionsThis study reports a population-based disease database, highlights the importance of diagnosis age in prognosis prediction, and suggests the role of renal manifestations in mortality. Furthermore, it corroborates recent TSC studies in the Asian population in terms of survival. Overall, physician vigilance, early diagnosis, and careful monitoring are beneficial for disease outcome and patient survival.

Highlights

Tuberous sclerosis complex (TSC) is an autosomal dominant disease with systemic manifestations, which can cause significant mortality and morbidity
Tuberous sclerosis complex (TSC) is a rare, autosomal dominant disease of variable penetrance, which results from mutations in the genes TSC1 or TSC2, respectively
Clinical hallmarks of TSC include characteristic dermatologic lesions; systemic benign neoplasms [4]; and hamartoma-associated manifestations, such as epilepsy, renal angiomyolipoma (AML), pulmonary lymphangioleiomyomatosis (LAM), and neuropsychiatric symptoms known as TSC-associated neuropsychiatric disorders (TAND) [1,2,3,4]

Summary

Introduction

Tuberous sclerosis complex (TSC) is an autosomal dominant disease with systemic manifestations, which can cause significant mortality and morbidity. Population-based epidemiological studies on TSC mortality and survival remain scarce, though several recent studies provide evidence that TSC survival rates are high and disease prognosis is fair for most patients. Tuberous sclerosis complex (TSC) is a rare, autosomal dominant disease of variable penetrance, which results from mutations in the genes TSC1 (which codes for hamartin) or TSC2 (which codes for tuberin), respectively. The severity of TSC varies substantially, with TSC2 mutations associated with more severe phenotypes, including learning disabilities and epilepsy, which are in turn associated with TAND [5]. A single-center British study [6] (n = 284) found significantly higher mortality in patients with learning disabilities (9% vs 2%), indicating the possible effects of genotype on survival rates. The location of mutation, severity of protein disruption, and somatic mutation of the wild-type copy may play a role [7]

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