Anne T Berg1,2, Hannah Palac3, Greta Wilkening4, Frank Zelko5,6, Leah Schust Meyer7. 1. Division of Neurology, Epilepsy Center, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. 2. Department of Pediatrics, Northwestern Feinberg School of Medicine, Chicago, IL, USA. 3. Data Solutions, REDCap Cloud, Encinitas, CA, USA. 4. Department of Neurology, Children's Hospital of Colorado, Aurora, CO, USA. 5. Pritzker Department of Psychiatry and Behavioral Health, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. 6. Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL, USA. 7. FamilieSCN2A Foundation, E. Longmeadow, MA, USA.
Abstract
OBJECTIVE: SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A-DEEs. METHODS: Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes. VABS scores obtained at study entry and yearly thereafter were analyzed for floor and ceiling effects, change with age, and association with epilepsy through use of regression and longitudinal regression methods. RESULTS: Sixty-four participants (50 with epilepsy, 30 [47%] female, median age 49 months, interquartile range [IQR] 28 to 101) were included. Histories of birth complications (N = 34, 54%), neonatal neurological signs (N = 45, 74%), and other neurological symptoms (N = 31, 48%) were common and similar in epilepsy and nonepilepsy subgroups. Mean standardized VABS scores (Composite 53.5; Motor, 55.8, Communication, 54.1, Socialization, 59.4, and Daily living skills, 55.1) reflected performance ~3 standard deviations below the normative test average. In longitudinal regression analyses, standardized scores decreased between 1.3 and 2.8 points per year, suggesting regression of abilities. Raw score analyses, however, revealed several subdomains with substantial floor effects (eg, community use); other raw scores increased with increasing age. Participants with epilepsy scored 0.6 to 1 SD lower than those without epilepsy (all P's < .05). SIGNIFICANCE: The VABS, as standardly administered, has shortcomings for addressing growth or regression in individuals with SCN2A-DEEs. Some subdomain raw scores reflected substantial floor effects. Raw scores increased so slowly over time that standardized scores declined. Alternative measures sensitive to incremental meaningful change are required if outcomes such as adaptive behavior are to be primary outcomes in short-term clinical trials.
OBJECTIVE:SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A-DEEs. METHODS: Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes. VABS scores obtained at study entry and yearly thereafter were analyzed for floor and ceiling effects, change with age, and association with epilepsy through use of regression and longitudinal regression methods. RESULTS: Sixty-four participants (50 with epilepsy, 30 [47%] female, median age 49 months, interquartile range [IQR] 28 to 101) were included. Histories of birth complications (N = 34, 54%), neonatal neurological signs (N = 45, 74%), and other neurological symptoms (N = 31, 48%) were common and similar in epilepsy and nonepilepsy subgroups. Mean standardized VABS scores (Composite 53.5; Motor, 55.8, Communication, 54.1, Socialization, 59.4, and Daily living skills, 55.1) reflected performance ~3 standard deviations below the normative test average. In longitudinal regression analyses, standardized scores decreased between 1.3 and 2.8 points per year, suggesting regression of abilities. Raw score analyses, however, revealed several subdomains with substantial floor effects (eg, community use); other raw scores increased with increasing age. Participants with epilepsy scored 0.6 to 1 SD lower than those without epilepsy (all P's < .05). SIGNIFICANCE: The VABS, as standardly administered, has shortcomings for addressing growth or regression in individuals with SCN2A-DEEs. Some subdomain raw scores reflected substantial floor effects. Raw scores increased so slowly over time that standardized scores declined. Alternative measures sensitive to incremental meaningful change are required if outcomes such as adaptive behavior are to be primary outcomes in short-term clinical trials.
Authors: Luciana Musante; Paola Costa; Caterina Zanus; Flavio Faletra; Flora M Murru; Anna M Bianco; Martina La Bianca; Giulia Ragusa; Emmanouil Athanasakis; Adamo P d'Adamo; Marco Carrozzi; Paolo Gasparini Journal: Genes (Basel) Date: 2022-03-12 Impact factor: 4.096
Authors: Jingliang Zhang; Xiaoling Chen; Muriel Eaton; Jiaxiang Wu; Zhixiong Ma; Shirong Lai; Anthony Park; Talha S Ahmad; Zhefu Que; Ji Hea Lee; Tiange Xiao; Yuansong Li; Yujia Wang; Maria I Olivero-Acosta; James A Schaber; Krishna Jayant; Chongli Yuan; Zhuo Huang; Nadia A Lanman; William C Skarnes; Yang Yang Journal: Cell Rep Date: 2021-08-03 Impact factor: 9.423