Article
Biochemistry & Molecular Biology
Yan-Ting Lu, Chung-Yao Hsu, Yo-Tsen Liu, Chung -Kin Chan, Yao-Chung Chuang, Chih-Hsiang Lin, Kai-Ping Chang, Chen-Jui Ho, Ching -Ching Ng, Kheng-Seang Lim, Meng -Han Tsai
Summary: This study aims to delineate the clinical and imaging spectrum that differentiates FLNA-positive and FLNA-negative PVNH patients. The results showed that FLNA mutations accounted for less than half of the PVNH patients, and FLNA-positive patients were more likely to have extra-cerebral features compared with FLNA-negative patients.
BIOMEDICAL JOURNAL
(2022)
Article
Neurosciences
Wenyu Liu, Hesheng Zhang, Xinyu Hu, Dong Zhou, Xintong Wu
Summary: This study combines univariate analysis and a Gaussian process classifier to assess local activity and explore neuropathological mechanisms in periventricular nodular heterotopia (PNH)-related epilepsy. The results reveal localized activity alterations in the left insula extending to the putamen and the subgenual anterior cingulate cortex extending to the orbitofrontal cortex in PNH-related epilepsy patients. Furthermore, the Gaussian process classifier achieved a high accuracy in classifying PNH patients from healthy controls.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Clinical Neurology
Karina Paliotti, Christelle Dassi, Saoussen Berrahmoune, Marlin Liz Bejaran, Carlos Eduardo Valera Davila, Ariadna Borras Martinez, Maria Carme Fons Estupina, Maria Margherita Mancardi, Antonella Riva, Thea Giacomini, Mariasevina Severino, Romina Romaniello, Francois Dubeau, Myriam Srour, Kenneth A. Myers
Summary: This study investigated the range of epilepsy phenotypes and the significance of specific brain malformation patterns in individuals with periventricular nodular heterotopia (PVNH). The study found that the epilepsy phenotypes in PVNH patients are diverse, and seizure patterns vary. However, the pattern of malformation can predict the course of epilepsy to some extent. Overall, approximately one quarter of affected individuals have drug-resistant epilepsy. The genetic etiologies identified are highly heterogeneous.
JOURNAL OF NEUROLOGY
(2023)
Editorial Material
Cell Biology
Ting Li, Ailing Li, Xin Pan
Summary: This study identifies KANSL1 as a crucial gene for macroautophagy/autophagy and shows that the FDA-approved drug 13-cis retinoic acid can alleviate mitophagic defects and neurobehavioral abnormalities in Kansl1 heterozygous mice. These findings provide a therapeutic strategy for the treatment of KdVS.
Review
Pediatrics
Lin Yang, GuangSheng Wu, HuiMei Yin, MengLan Pan, YaFei Zhu
Summary: This article described a case of PNH associated with a FLNA gene mutation in exon 31, q28 region of the X chromosome. The patient did not have seizures, congenital heart disease, lung disease, skeletal or joint issues, and had normal development. The characterization of FLNA will aid in the clinical diagnosis and treatment of PNH and provide personalized genetic counseling for patients.
Article
Biochemistry & Molecular Biology
Miya St John, Olivia van Reyk, David A. Koolen, Bert B. A. de Vries, David J. Amor, Angela T. Morgan
Summary: This study provides a detailed characterization of speech and language impairment in Koolen-de Vries syndrome (KdVS). It defines the medical and neurodevelopmental phenotype in the largest cohort of KdVS individuals to date, highlighting the core features of intellectual disability, eye anomalies, structural brain anomalies, and dental problems. While most individuals with KdVS can speak, some use augmentative and alternative communication methods. The study also reveals relative weaknesses in language, literacy, and social skills, and relative strengths in social competence and coping skills.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Clinical Neurology
Valerio Frazzini, Stephen Whitmarsh, Katia Lehongre, Pierre Yger, Jean-Didier Lemarechal, Bertrand Mathon, Claude Adam, Dominique Hasboun, Virginie Lambrecq, Vincent Navarro
Summary: Periventricular nodular heterotopia (PNH) is a malformation of cortical development that often leads to drug-resistant epilepsy. In this study, consistent interictal patterns were identified within the nodules, with specific patterns associated with seizure generation. The results suggest that PNH nodules may play a significant role in initiating seizures.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Nicolin Hainc, Paula Alcaide-Leon, Robert A. Willinsky, Timo Krings, Patrick Nicholson
Summary: This study used conventional MRI techniques to identify transmantle bands connecting ectopic nodules to overlying cortex in patients with periventricular nodular heterotopia (PNH). The findings suggest that conventional MRI scans can provide similar results as advanced MRI techniques in detecting this abnormal connection.
Article
Behavioral Sciences
Flavius-Ionut Bratu, Irina Oane, Andrei Barborica, Cristian Donos, Constantin Pistol, Andrei Daneasa, Camelia Lentoiu, Ioana Mindruta
Summary: The study focuses on the brain network involved in autoscopic hallucination elicited by electrical stimulation of PVNH in a drug resistant epilepsy patient. The results demonstrate that electrical high frequency stimulation of PVNH mainly induces autoscopic hallucinations related to the face and upper trunk, while multi-modal connectivity analysis identifies the specific brain regions involved.
Article
Genetics & Heredity
Deepti Saxena, Amita Moirangthem, Arya Shambhavi, Shubha R. Phadke
Summary: Koolen-de Vries syndrome is a recurrent microdeletion syndrome caused by deletion of a 400-600 kb region at 17q21.31, leading to typical facial features, varying degrees of intellectual disability, seizures, and behavioral issues. This is the first case report of Koolen-de Vries syndrome from India.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Clinical Neurology
S. Yimenicioglu, A. Kocaaga
Summary: This study reports the first case of Koolen-de Vries syndrome in Turkey, characterized by intellectual disability, developmental delay, epilepsy, and dysmorphic facial features. The genetic mutation in the KANSL1 gene was identified.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2022)
Article
Genetics & Heredity
Arianne Bouman, Romy N. Bouwmeester, Leo A. van Vlimmeren, Pauline Burger, Jean-Louis Mandel, Bert B. A. de Vries, Marinus de Kleuver, Willemijn M. Klein, Joyce M. Geelen, David A. Koolen
Summary: Koolen-de Vries syndrome (KdVS) is a multisystem disorder characterized by developmental delay, intellectual disability, characteristic facial features, epilepsy, cardiovascular and urogenital malformations, and various musculoskeletal disorders. Scoliosis is a common feature. This study aims to provide recommendations for the management and follow-up of scoliosis in individuals with KdVS.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Neurosciences
Yurui Guo, Alpen Ortug, Rodney Sadberry, Arthur Rezayev, Jacob Levman, Tadashi Shiohama, Emi Takahashi
Summary: This study aimed to identify symptom-related neuroimaging biomarkers for patients with dysgenesis of the corpus callosum (dCC), revealing differential links between brain volumes and structures and various symptoms. Specifically, left hemisphere GI abnormality could serve as a predictor for the disease.
Article
Neurosciences
Yayue Gao, Guanpeng Chen, Pengfei Teng, Xin Zhang, Fang Fang, Dario J. Englot, Guoming Luan, Xiongfei Wang, Qian Wang
Summary: PVNH is a developmental disorder characterized by failed neuronal migration, forming ectopic neuronal nodules along the ventricular walls. This study used MEG and sEEG recordings to investigate the functional communication between PVNH tissue and the neocortex. The results showed that PVNH tissue is functionally integrated into cognition-related cortical circuits and can modulate local neural activity in sensory areas.
Article
Genetics & Heredity
Carla De Angelis, Alicia B. Byrne, Rebecca Morrow, Jinghua Feng, Thuong Ha, Paul Wang, Andreas W. Schreiber, Milena Babic, Ajay Taranath, Nick Manton, Sarah L. King-Smith, Quenten Schwarz, Peer Arts, Hamish S. Scott, Christopher Barnett
Summary: This study reported a fetus with extensive posterior PNH associated with biallelic variants in LAMC3, providing valuable insights into the genetic cause of posterior PNH. The findings extend the cortical phenotype associated with LAMC3 mutations and suggest that the identified LAMC3 variants may be causal of PNH in this fetus.
BMC MEDICAL GENOMICS
(2021)
Article
Clinical Neurology
Kelly G. Knupp, Ingrid E. Scheffer, Berten Ceulemans, Joseph Sullivan, Katherine C. Nickels, Lieven Lagae, Renzo Guerrini, Sameer M. Zuberi, Rima Nabbout, Kate Riney, Anupam Agarwal, Michael Lock, David Dai, Gail M. Farfel, Bradley S. Galer, Arnold R. Gammaitoni, Shikha Polega, Ronald Davis, Antonio Gil-Nagel
Summary: Long-term use of fenfluramine showed sustained reduction in drop seizure frequency in LGS patients, with significant reduction in the frequency of GTCS and tonic seizures. The drug was generally well tolerated with minimal adverse effects and no significant cardiac side effects observed. Fenfluramine may serve as an important long-term treatment option for patients with LGS.
Article
Biochemistry & Molecular Biology
Bart P. G. H. van der Sanden, Gaby Schobers, Jordi Corominas Galbany, David A. Koolen, Margje Sinnema, Jeroen van Reeuwijk, Connie T. R. M. Stumpel, Tjitske Kleefstra, Bert B. A. de Vries, Martina Ruiterkamp-Versteeg, Nico Leijsten, Michael Kwint, Ronny Derks, Hilde Swinkels, Amber den Ouden, Rolph Pfundt, Tuula Rinne, Nicole de Leeuw, Alexander P. Stegmann, Servi J. Stevens, Arthur van den Wijngaard, Han G. Brunner, Helger G. Yntema, Christian Gilissen, Marcel R. Nelen, Lisenka E. L. M. Vissers
Summary: Genome sequencing (GS) is a technique that can provide novel diagnoses for patients who remain undiagnosed. In a study involving patients with neurodevelopmental disorders, GS and standard of care (SOC) had similar diagnostic yield, but GS identified two additional conclusive diagnoses and four additional possible diagnoses. GS comprehensively identified all variants in a single experiment, suggesting it is a more efficient genetic diagnostic workflow.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Lottie D. Morison, Elisabeth Meffert, Miriam Stampfer, Irene Steiner-Wilke, Brigitte Vollmer, Katrin Schulze, Tracy Briggs, Ruth Braden, Adam Vogel, Daisy Thompson-Lake, Chirag Patel, Edward Blair, Himanshu Goel, Samantha Turner, Ute Moog, Angelika Riess, Frederique Liegeois, David A. Koolen, David J. Amor, Tjitske Kleefstra, Simon E. Fisher, Christiane Zweier, Angela T. Morgan
Summary: Disruptions of FOXP2 can cause severe speech disorder known as childhood apraxia of speech (CAS). This study examined individuals with pathogenic FOXP2-only variants and found that speech disorders, including CAS, were prevalent in these cases. Other comorbidities such as feeding difficulties, motor impairment, anxiety, depression, and sleep disturbance were also observed. The study emphasizes the importance of FOXP2 in understanding the neurobiological basis of speech disorder.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Antony Kaspi, Michael S. Hildebrand, Victoria E. Jackson, Ruth Braden, Olivia van Reyk, Tegan Howell, Simone Debono, Mariana Lauretta, Lottie Morison, Matthew J. Coleman, Richard Webster, David Coman, Himanshu Goel, Mathew Wallis, Gabriel Dabscheck, Lilian Downie, Emma K. Baker, Bronwyn Parry-Fielder, Kirrie Ballard, Eva Harrold, Shaun Ziegenfusz, Mark F. Bennett, Erandee Robertson, Longfei Wang, Amber Boys, Simon E. Fisher, David J. Amor, Ingrid E. Scheffer, Melanie Bahlo, Angela T. Morgan
Summary: This study identified new candidate genes associated with childhood apraxia of speech (CAS) through genome sequencing and bioinformatic analysis. The findings highlight the roles of chromatin organization and gene regulation in CAS, and confirm co-expression of CAS-related genes during brain development.
MOLECULAR PSYCHIATRY
(2023)
Editorial Material
Clinical Neurology
Rohit R. Das, Adeline L. Goss, Ingrid E. Scheffer
ANNALS OF NEUROLOGY
(2023)
Article
Genetics & Heredity
Alanna Strong, Soumya Rao, Sandra von Hardenberg, Dong Li, Liza L. Cox, Paul C. Lee, Li Q. Zhang, Waheed Awotoye, Tamir Diamond, Jessica Gold, Catherine Gooch, Lord Jephthah Joojo Gowans, Hakon Hakonarson, Anne Hing, Kathleen Loomes, Nicole Martin, Mary L. Marazita, Tarja Mononen, David Piccoli, Rolph Pfundt, Salmo Raskin, Stephen W. Scherer, Nara Sobriera, Courtney Vaccaro, Xiang Wang, Deborah Watson, Rosanna Weksberg, Elizabeth Bhoj, Jeffrey C. Murray, Andrew C. Lidral, Azeez Butali, Michael F. Buckley, Tony Roscioli, David A. Koolen, Laurie H. Seaver, Cynthia A. Prows, Rolf W. Stottmann, Timothy C. Cox
Summary: AMOTL1 encodes angiomotin-like protein 1, a protein that regulates cell polarity, adhesion, and migration. Variants in AMOTL1 are associated with orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations. The study suggests that missense variants in AMOTL1, particularly in the region affecting amino acids 157-161, define a new orofacial clefting syndrome and highlight the importance of this region in its function.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Clinical Neurology
Alice M. Donnan, Amy L. Schneider, Sophie Russ-Hall, Leonid Churilov, Ingrid E. Scheffer
Summary: This study aims to describe the proportions of patients with commonly encountered genetic developmental and epileptic encephalopathies (DEEs) who developed convulsive status epilepticus (CSE), nonconvulsive status epilepticus (NCSE), and sudden unexplained death in epilepsy (SUDEP). The findings showed that the proportions of these serious presentations vary for different genetic DEEs. These results have important implications for early diagnosis, management, and disease-specific counseling for this high-risk group of conditions.
Article
Genetics & Heredity
Elise Brimble, Kathryn G. Reyes, Kopika Kuhathaas, Orrin Devinsky, Maura R. Z. Ruzhnikov, Xilma R. Ortiz-Gonzalez, Ingrid Scheffer, Nadia Bahi-Buisson, Heather Olson
Summary: By evaluating 122 individuals in a patient registry, we have refined the clinical spectrum of FOXG1 syndrome and expanded genotype-phenotype correlations. Core features of the syndrome include delayed or absent developmental milestones, seizures, and movement disorders. Missense variants are associated with milder clinical courses and better developmental outcomes compared to gene deletions and nonsense variants, which are associated with more severe phenotypes and higher seizure burden.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Antonio Giulio Gennari, Dorottya Cserpan, Ilona Stefanos-Yakoub, Raimund Kottke, Ruth O'Gorman Tuura, Georgia Ramantani
Summary: This study investigated the potential of diffusion tensor imaging (DTI) in paediatric structural epilepsy associated with focal cortical dysplasia (FCD). The results showed that DTI indices can differentiate between FCD and contralateral brain parenchyma (CBP), and that clinical features have an impact on these indices.
INSIGHTS INTO IMAGING
(2023)
Review
Pediatrics
Mario Mastrangelo, Valentina Gasparri, Katerina Bernardi, Silvia Foglietta, Georgia Ramantani, Francesco Pisani
Summary: A systematic review of published pediatric cases with vitamin B6-dependent epilepsy showed that this condition is characterized by early onset, diverse seizure types, and responsiveness to vitamin B6 supplementation.
Article
Cardiac & Cardiovascular Systems
Elizabeth D. Paratz, Ingrid E. Scheffer, Christopher Semsarian
Summary: This review examines the significance of seizures in young athletes and the complex inter-relationship between seizures, epilepsy, and sudden cardiac death. Recent findings suggest that epilepsy may be associated with sudden unexplained cardiac death, with some patients experiencing a cardiocerebral channelopathy. It is important to consider the possibility of misdiagnosis of cardiac syncope in athletes with a history of seizures, requiring careful cardiac evaluation and risk stratification. Further investigation is needed to fully understand the association between seizures and young sudden cardiac death.
CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Clinical Neurology
Rebekah V. Harris, Karen L. Oliver, Piero Perucca, Pasquale Striano, Angelo Labate, Antonella Riva, Bronwyn E. Grinton, Joshua Reid, Jessica Hutton, Marian Todaro, Terence J. O'Brien, Patrick Kwan, Lynette G. Sadleir, Saul A. Mullen, Emanuela Dazzo, Douglas E. Crompton, Ingrid E. Scheffer, Melanie Bahlo, Carlo Nobile, Antonio Gambardella, Samuel F. Berkovic
Summary: This study analyzed 134 families with familial mesial temporal lobe epilepsy (FMTLE) and found that FMTLE is a generally mild drug-responsive syndrome with the main symptom being déjà vu. Unlike monogenic focal epilepsy syndromes, molecular data supports a polygenic basis for FMTLE. The polygenic risk score (PRS) data suggests that sub-genome-wide significant focal epilepsy genome-wide association study single nucleotide polymorphisms are important risk variants for FMTLE.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Sterre Van der Veen, Gabrielle T. W. Tse, Alessandro Ferretti, Giacomo Garone, Bart Post, Nicola Specchio, Victor S. C. Fung, Marina Trivisano, Ingrid E. Scheffer
Summary: In patients with genetic DEEs, a variety of MDs are present, with stereotypies and dystonia being the most common. Different biological mechanisms may lead to different types of MDs.
Editorial Material
Clinical Neurology
Zimeng Ye, Sufang Lin, Xia Zhao, Mathew Wallis, Xinyi Gao, Li Sun, Jiarui Wu, Jing Duan, Yi Yao, Lin Li, Li Chen, Dezhi Cao, Zhanqi Hu, Victor W. Zhang, Samuel F. Berkovic, Ingrid E. Scheffer, Jianxiang Liao, Michael S. Hildebrand
PEDIATRIC NEUROLOGY
(2024)
Article
Health Care Sciences & Services
Leopold Simma, Fabrizio Romano, Steffen Schmidt, Georgia Ramantani, Bigna K. Bolsterli
Summary: Central nervous system (CNS) disorders are common in critically ill children, with non-convulsive status epilepticus (NCSE) often being unrecognized but significantly impacting neurological outcomes and hospitalization. We developed a simplified point-of-care EEG recording method (pocEEG) for pediatric emergency departments to enable timely diagnosis and treatment initiation when standard EEG is not readily available.
JOURNAL OF PERSONALIZED MEDICINE
(2023)