title: The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge, UK. jrwy1@cam.ac.uk
authors.forename: John R W
authors.initials: JR
authors.lastname: Yates
authors.forename: Cathy
authors.initials: C
authors.lastname: Maclean
authors.forename: J Nicholas P
authors.initials: JN
authors.lastname: Higgins
authors.forename: Ayla
authors.initials: A
authors.lastname: Humphrey
authors.forename: Kate
authors.initials: K
authors.lastname: le Maréchal
authors.forename: Michelle
authors.initials: M
authors.lastname: Clifford
authors.forename: Iris
authors.initials: I
authors.lastname: Carcani-Rathwell
authors.forename: Julian R
authors.initials: JR
authors.lastname: Sampson
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Bolton
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation; D007690:Polycystic Kidney Diseases / Q000209:etiology; D011379:Prognosis; D012640:Seizures / Q000209:etiology; D014402:Tuberous Sclerosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics; D016216:Ultrasonography, Prenatal
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins