The Dup15q Alliance and the Angelman Syndrome Foundation are excited to announce a jointly funded research project that will build the first 3D structure of UBE3A. Gilles Trave, PhD from the European Center of Research and Biology in Illkirch, France will study the interaction between UBE3A and HERC2 proteins to regulate important genes for neurodevelopment and better understand how UBE3A and HERC2 work together. Dr. Trave hopes to gain an understanding of how UBE3A works with HERC2 to impact brain development and will build the first ever 3D structure of UBE3A with and without HERC2.
Linda C.Lauxa, E. Martina Bebinb, Daniel Checkettsc, Michael Chezd, Robert Flaminie, Eric D.Marshf, Ian Millerg, Kathryn Nicholh,Yong Parki, Eric Segalj, Laurie Seltzerk, Jerzy P.Szaflarskib, Elizabeth A. Thielel, Arie Weinstockm, on behalf of CBD EAP study group
Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.
Authors: Joel Frohlich1,2,3* , Lawrence T. Reiter4 , Vidya Saravanapandian2 , Charlotte DiStefano2 , Scott Huberty2,5, Carly Hyde2 , Stormy Chamberlain6 , Carrie E. Bearden7 , Peyman Golshani8 , Andrei Irimia9 , Richard W. Olsen10, Joerg F. Hipp1† and Shafali S. Jeste2†
Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype.
Neurodevelopmental disorders (NDDs) affect 7–14% of all children in developed countries and are one of the leading causes of lifelong disability. Epigenetic modifications are poised at the interface between genes and environment and are predicted to reveal insight into NDD etiology.
Authors: Chloe Verducci, BA, Fizza Hussain, MS, Elizabeth Donner, MD FRCP(C), Brian D. Moseley, MD, Jeffrey Buchhalter, MD, Dale Hesdorffer, PhD, Daniel Friedman, MD, MSc, and Orrin Devinsky, MD
There were 237 definite and probable cases of SUDEP among 530 NASR participants. SUDEP decedents had a median age of 26 (range 1–70) years at death, and 38% were female. In 143 with sufficient information, 40% had generalized and 60% had focal epilepsy. SUDEP affected the full spectrum of epilepsies, from benign epilepsy with centrotemporal spikes (n = 3, 1%) to intractable epileptic encephalopathies (n = 27, 11%). Most (93%) SUDEPs were unwitnessed; 70% occurred during apparent sleep; and 69% of patients were prone. Only 37% of cases of SUDEP took their last dose of antiseizure medications (ASMs). Reported lifetime generalized tonic-clonic seizures (GTCS) were <10 in 33% and 0 in 4%.
We report 13 SUDEP cases in the North American SUDEP Registry with both psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) among a consecutive series of 231 cases (excluding epileptic encephalopathies). On average, cases of PNES + ES died at a younger age (23 ± 11 years) than the ES‐only cohort (30 ± 14 years), and died an average of 3 years after PNES diagnosis. We found no statistically significant confounding cardiac, respiratory, or psychiatric comorbidities and equal rates of anti‐seizure medication adherence, although there was a trend for higher rates of psychiatric disorders in the PNES group. Our findings confirm that patients with comorbid ES and PNES can die from SUDEP and that there may be a high‐risk period after the diagnosis of PNES is made in patients with comorbid ES. Such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).
Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Several genetic causes of ASD have been identified and this has enabled researchers to construct mouse models. Mouse behavioral tests reveal impaired social interaction and communication, as well as increased repetitive behavior and behavioral inflexibility in these mice, which correspond to core behavioral deficits observed in individuals with ASD.
Joel Frohlich, Meghan T.Miller, Lynne M. Bird, Pilar Garces, Hannah Purtell, Marius C. Hoener, Benjamin D.Philpot, Michael S.Sidorov, Wen-HannTan, Maria-Clemencia Hernandez, Alexander Rotenberg, Shafali S.Jeste, Michelle Krishnana, Omar Khwajaa Joerg F. Hippa
BACKGROUND:Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions ofthe geneUBE3Aor deletion of chromosome 15 at 15q11-q13, which encompassesUBE3Aand several other genes,includingGABRB3,GABRA5,GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (b3,a5,g3).Individuals with deletions are generally more impaired than those with other genotypes, but the underlyingpathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesisthat genes other thanUBE3Alocated on 15q11-q13 cause differences in pathophysiology between AS genotypes
Charlotte Distefano, Rujuta Wilson, Shafali Jeste
Objective: To systematically assess developmental and behavioral characteristics in a large cohort of children with dup15q syndrome to identify clinical endpoints for future clinical trials.