Correction to: Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study.

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Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study.

BACKGROUND: Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited. METHODS: Prospective, national surveillance study in Germany over a 2-year-period (03/2015-02/2017) using current revised criteria for TSC. Patients up to the age of 18 years with a new diagnosis of definite or possible TSC (clinical and/or genetic) were included. The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data. RESULTS: In total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6 months (range: 5 months before birth - 197 months of age). Among patients identified with features of TSC, 73.3% met criteria for definite diagnosis (median age: 7 months) and 26.7% met criteria for a possible diagnosis (median age: 3 months). 55.8% of patients were male. When excluding prenatally diagnosed patients, median age at diagnosis was 11 months with a range of 0 to 197 months. The 3 most common clinical features at diagnosis of TSC were central nervous system involvement in 73.3% patients (of these 95.2% experienced seizures), cutaneous involvement in 58.1% patients (with the most common lesion being hypomelanotic macules in 92%) and cardiac rhabdomyoma in half of the patients. Cardiac rhabdomyoma were detected by prenatal ultrasonography in 22.1% of patients. The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in 25.6% (about 13% of all diagnosed patients) in our cohort. The overall prevalence of seizure disorders was 69.8%. The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.760-1:13.520 live births in Germany. CONCLUSIONS: This is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012. This prospective surveillance study demonstrates a low age at first diagnosis (median: 6 months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage.

[ESPED-Survey: TSC-disease in children and adolescents: preliminary results from a German epidemiological survey]. / ESPED-Erhebung: TSC-Erkrankung bei Kindern und Jugendlichen: eine einjährige Interim-Analyse.

BACKGROUND: Tuberous sclerosis complex (TSC) disease is a rare genetic, multi-organ disorder characterized by the occurrence of multiple hamartoma. METHODS: In cooperation with ESPED, Germany, a prospective, epidemiological study was performed to assess the incidence of newly diagnosed TSC disease in patients ≤18 years in Germany. Moreover, the following parameters were assessed: 1. Age distribution at initial diagnosis; 2. Percentage of patients with in utero diagnosis of TSC; 3. Detailed description of pathological clinical findings; 4. Results from genetic testing. RESULTS: In this one-year interim analysis, 84 electronic questionnaires were received, 17 of which did not contain complete sets of data and were not included in data analysis. Twenty-three of 67 questionnaires did not report TSC patients and 3 reports contained redundant data sets and were excluded. In total, 41 reports were included into data analysis (female: 23; male: 18); median age at first diagnosis was 6 months (range: 0-151 months). The three most common symptoms were: central nervous affection: 31/41 patients ((75.6 %); 29/31 with seizures); rhabdomyoma: in 20/41 (48.8 %); cutaneous affection: hypomelanotic maculae ("white spots"): 20/41 (48.8 %). The three following organ manifestations were seen most often in a comprehensive diagnostic work-up: rhabdomyoma: 23/41 ((56.1 %); cortical dysplasia: 22/41 (53.7 %); "white spots"): 20/41 (48.8 %). In 11/41 patients, cardiac rhabdomyoma were detected by ultrasonography prenatally. In 6 patients, a TSC-2 mutation was found while in 4 patients a TSC-1 mutation was noted; in 1 patient, genetic testing was negative. CONCLUSIONS: Based on our preliminary findings, the annual incidence rate for TSC disease is estimated at approximately 1:12,300 live births, but this is a very rough approximation.