BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%-80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations. METHODS: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures. RESULTS: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication. DISCUSSION: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.
BACKGROUND:Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%-80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations. METHODS: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures. RESULTS: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication. DISCUSSION: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.
Authors: Le Jian; Lakshmi Nagarajan; Nicholas de Klerk; David Ravine; John Christodoulou; Helen Leonard Journal: Eur J Paediatr Neurol Date: 2007-04-11 Impact factor: 3.140
Authors: J L Neul; P Fang; J Barrish; J Lane; E B Caeg; E O Smith; H Zoghbi; A Percy; D G Glaze Journal: Neurology Date: 2008-03-12 Impact factor: 9.910
Authors: Daniel C Tarquinio; Wei Hou; Jeffrey L Neul; Walter E Kaufmann; Daniel G Glaze; Kathleen J Motil; Steven A Skinner; Hye-Seung Lee; Alan K Percy Journal: Pediatr Neurol Date: 2015-06-26 Impact factor: 3.372
Authors: Christopher S Ward; E Melissa Arvide; Teng-Wei Huang; Jong Yoo; Jeffrey L Noebels; Jeffrey L Neul Journal: J Neurosci Date: 2011-07-13 Impact factor: 6.167
Authors: Daniel C Tarquinio; Wei Hou; Jeffrey L Neul; Gamze Kilic Berkmen; Jana Drummond; Elizabeth Aronoff; Jennifer Harris; Jane B Lane; Walter E Kaufmann; Kathleen J Motil; Daniel G Glaze; Steven A Skinner; Alan K Percy Journal: Brain Dev Date: 2018-04-12 Impact factor: 1.961
Authors: Nikolaos Mellios; Jonathan Woodson; Rodrigo I Garcia; Benjamin Crawford; Jitendra Sharma; Steven D Sheridan; Stephen J Haggarty; Mriganka Sur Journal: Proc Natl Acad Sci U S A Date: 2014-06-23 Impact factor: 11.205
Authors: Daniel Charles Tarquinio; Kathleen J Motil; Wei Hou; Hye-Seung Lee; Daniel G Glaze; Steven A Skinner; Jeff L Neul; Fran Annese; Lauren McNair; Judy O Barrish; Suzanne P Geerts; Jane B Lane; Alan K Percy Journal: Neurology Date: 2012-10-03 Impact factor: 9.910