Diagnostic flow analysis of tuberous sclerosis complex in Japan: a retrospective claims database study.

BACKGROUND

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder that affects multiple organs. However, precise diagnosis is challenging owing to the lack of truly pathognomonic symptoms. This retrospective observational study aimed to explore the real-world diagnostic flow of Japanese patients with TSC by examining time to diagnosis (TTD) from the onset of each TSC-related manifestation to TSC diagnosis and the role of TSC clinic in timely diagnosis, using data from a health insurance database.

METHODS

Analyses were performed using data derived from the JMDC Claims Database between January 2005 and December 2020. Patients with at least 1 confirmed diagnosis of TSC were stratified into 2 cohorts: Cohort 1 included cases diagnosed after 2 years of age, and Cohort 2 included cases diagnosed before 2 years of age. The primary endpoint was TTD in Cohorts 1 and 2. Secondary endpoints were the incidence of each manifestation in Cohort 1 and the incidence and risk ratios of TSC-unrelated symptoms in Cohort 2.

RESULTS

Cohorts 1 and 2 included 106 and 42 patients, respectively. In Cohort 1, patients with a renal tumor diagnosis as a primary TSC-related manifestation had the longest TTD with a wide range (median: 23 months to up to 91 months); patients with non-specific TSC-related manifestations such as brain tumor/intraventricular tumor, epilepsy, or intellectual disabilities also experienced a delay in TTD. In patients with TSC who developed epilepsy, those attending facilities with a TSC clinic were diagnosed with TSC more quickly than those attending facilities without a TSC clinic (median: 11.5 and 19.0 months, respectively; p = 0.0379). Epilepsy was the manifestation with the highest incidence (29.2%) among Cohort 1 patients, while cardiac rhabdomyoma had the highest incidence (54.8%) among Cohort 2 patients. Dry skin was the most common TSC-unrelated symptom in Cohort 2, with a 1.7-fold higher incidence rate than that in controls (N = 619,936).

CONCLUSION

Japanese patients with renal lesions as a primary TSC-related manifestation had the longest delay for a definitive diagnosis of TSC, followed by those with epilepsy, brain tumor/intraventricular tumor, and intellectual disabilities. The TSC clinic played an important role in the early diagnosis of TSC.