Aims The Tuberous Sclerosis 2000 Study is the first comprehensive longitudinal study of tuberous sclerosis (TS) and aims to identify factors that determine prognosis. Mode of presentation and findings at initial assessments are reported here.
Methods Children aged 0–16 years newly diagnosed with TS in the UK were evaluated.
Results 125 children with TS were studied. 114 (91%) met clinical criteria for a definite diagnosis and the remaining 11 (9%) had pathogenic TSC1 or TSC2 mutations. In families with a definite clinical diagnosis, the detection rate for pathogenic mutations was 89%. 21 cases (17%) were identified prenatally, usually with abnormalities found at routine antenatal ultrasound examination. 30 cases (24%) presented before developing seizures and in 10 of these without a definite diagnosis at onset of seizures, genetic testing could have confirmed TS. 77 cases (62%) presented with seizures. Median age at recruitment assessment was 2.7 years (range: 4 weeks–18 years). Dermatological features of TS were present in 81%. The detection rate of TS abnormalities was 20/107 (19%) for renal ultrasound including three cases with polycystic kidney disease, 51/88 (58%) for echocardiography, 29/35 (83%) for cranial CT and 95/104 (91%) for cranial MRI. 91% of cases had epilepsy and 65% had intellectual disability (IQ<70).
Conclusions Genetic testing can be valuable in confirming the diagnosis. Increasing numbers of cases present prenatally or in early infancy, before onset of seizures, raising important questions about whether these children should have EEG monitoring and concerning the criteria for starting anticonvulsant therapy.
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Funding The authors thank the Tuberous Sclerosis Association and The Isaac Newton Trust for funding this study. PB is supported by the UK NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London and The South London and Maudsley NHS Foundation Trust.
Competing interests None.
Ethics approval The study was approved by West Midlands Multi-Centre Research Ethics Committee and by local research ethics committees for the participating centres.
Provenance and peer review Not commissioned; externally peer reviewed.
Members of the Tuberous Sclerosis 2000 Study Group not individually listed in the authorship are as follows: V Attard, A Clarke, FV Elmslie, AK Saggar, St George's Hospital, London; D Baines, BA Kerr, Royal Manchester Children's Hospital, Manchester; C Brayne, Institute of Public Health, University of Cambridge; C Connolly, A Lydon, C Srivastava, Institute of Psychiatry, King's College London; JA Cook, Sheffield Children's Hospital, Sheffield; C Falconer, St James's University Hospital, Leeds; DM Davies, Institute of Medical Genetics, Cardiff; AE Fryer, Alder Hey Children's Hospital, Liverpool; M Haslop, Y Granader*, University of Cambridge (*currently Yeshiva University, New York); PD Griffiths, University of Sheffield; A Hunt, Tuberous Sclerosis Association; WWK Lam, Western General Hospital, Edinburgh; JC Kingswood, Royal Sussex County Hospital, Brighton; ZH Miedzybrodzka, College of Life Sciences and Medicine, Aberdeen; H Crawford, PJ Morrison, Belfast City Hospital; BGR Neville, UCL Institute of Child Health, London; FJK O'Callaghan, University of Bristol; SG Philip, Birmingham Children's Hospital, Birmingham; S Seri, Aston Brain Centre, School of Life and Health Sciences, Aston University, Birmingham; R Sheehan-Dare, The General Infirmary, Leeds; CH Shepherd, Craigavon Area Hospital, Craigavon.