qEEG. The electroencephalogram is one of the oldest tools in neurology. We use it every day to diagnose and monitor brain function, yet, even in the era of genomic medicine, most of our EEG interpretation still relies on visual inspection, a human reading of squiggled traces. In a recent publication in Neurology, we asked whether the information embedded in these signals could be measured more objectively in children with STXBP1, SCN1A, and SYNGAP1-related disorders. Here is the story on how we identified hidden signals in the EEG tracings of individuals with genetic epilepsies.
Tag Archives: SYNGAP1
The edge of SYNGAP1 – familial variants in a complex neurodevelopmental disorder
Bridge the gap. There are very few conditions that I have learned as much about in the last three years as SYNGAP1-related disorders. We just passed the critical milestone of 100 SYNGAPians followed in our clinical trial–grade natural history study (SYNGAP1 ProMMiS). In addition, our study using real-world data across more than 2,500 patient years came online earlier this year. We are becoming more familiar with the range of reflex seizures observed in this condition and the unique fingerprint on the sensory profile that characterize its behavioral features. In a recent publication, we explored another aspect of SYNGAP1 that had been neglected so far. We tried to understand what happens when SYNGAP1 variants run in families and what this means for trial readiness and precision therapies.
STXBP1 and SYNGAP1 Natural History – Reflections after Day 1 of ENDD Clinic
A big step forward. Disease natural history and clinical trial readiness are constantly discussed topics in the rare genetic epilepsy space. Additionally, these concepts have driven our work in the Helbig lab since the very beginning. So why then did last week’s launch of our group’s first prospective natural history study of STXBP1 and SYNGAP1 feel like such a monumental step forward? Last week, we evaluated our first participants in the prospective natural history study that is part of the newly established Center for Epilepsy and Neurodevelopmental Disorders (ENDD), and here are some reflections from our team.
The future of biomarker development in rare disease
CNS Biomarkers. In the last two days, our team attended the Workshop for Multimodal Biomarkers in CNS Disorders held at the National Academies of Sciences, Engineering, and Medicine in Washington, DC. This conference provided a needed review of the current state of multimodal biomarker discovery and development. While most of the speakers focused on more common CNS disorders such as Alzheimer’s disease and neuropsychiatric disorders, there stands to be important lessons that can be translated into the rare disease field. Here is what we learned about the clinical utility of biomarkers and their potential as we move towards precision medicine in rare disease.
Artificial intelligence in epilepsy – the rare disease perspective
Breckenridge. This week, our team attended the first conference for Artificial Intelligence in Epilepsy in Breckenridge, Colorado. I was honored to be one of the two speakers representing the epilepsy genetics field, trying to build the bridge between the impressive amount of research in machine learning and EEG analysis with our current progress and research efforts in the genetic epilepsies. In this blog post, I would like to summarize some of my impressions from this meeting and discuss two aspects where rare disease research and machine learning already intersect, namely seizure forecasting and virtual clinical trials.
SYNGAP1 – three things to know in 2023
Postsynaptic. SYNGAP1-related disorders are among the most common genetic developmental and epileptic encephalopathies with a unique clinical presentation. However, since the initial gene discovery in 2009, the clinical spectrum has expanded significantly to include a wider range of epilepsies and seizure types. Additionally, the SYNGAP1 community has grown to encompass hundreds of individuals reported in the literature or organized in advocacy organizations. Accordingly, we wanted to use the opportunity to update our SYNGAP1 page. Here are three things to know about SYNGAP1 in 2023.
Sequencing for developmental disorders on a national level – the DDD(UK) study
DDD. It’s probably the most impressive of all exome sequencing studies of 2014 and I almost missed it. Late December last year, the Deciphering Developmental Disorders study was published in Nature, reporting the genetic findings in more than 1,000 patient-parent trios, which were collected in a systematic nation-wide approach in the United Kingdom and Ireland. The analysis of more than 1,600 de novo mutations in this cohort provides another fascinating view into the genetics of neurodevelopmental disorders, independently confirming the role of DNM1 and pointing out several genes that act through either activating or dominant-negative mutations. Let me guide you through a study that comes to the sobering conclusion that even entire nations are too small to understand the genetics of neurodevelopmental disease. Continue reading
SCN8A encephalopathy – and how it differs from Dravet Syndrome
Nav1.6. For some reason, SCN8A always met some resistance. In contrast to other epilepsy genes, it took a while for the community to embrace this gene as a genuine cause of epileptic encephalopathies. A recent publication in Neurology now investigates the phenotypic spectrum of SCN8A encephalopathy – and points out important features that distinguish this condition from Dravet Syndrome. Continue reading
TADA – a joint analysis of de novo and inherited risk factors in autism
Beyond de novo. One of the most robust ways to interpret exome data is the analysis of de novo mutations. However, in addition to the 1-2 de novo events that we can identify in every individual, there is a plethora of inherited variants that often look suspicious. Unfortunately, other than looking at monogenic recessive disorders, we are often incapable of understanding the importance of these inherited variants and tend to ignore them. A recent publication in Nature now overcomes this difficulty by applying a joint analysis of inherited and de novo variants in autism. Continue reading
The 1003 possible autism genes – a matter of constraint
Overview. There have been numerous publications on de novo mutations in autism and intellectual disability over the last three years. Many of these studies struggle to distinguish signal from noise, and the plethora of findings leaves the reader wondering which genes are bona fide autism genes and in which cases the evidence is limited. A recent paper in Nature Genetics uses a new metric to assess expected versus observed de novo mutations in more than published 1000 autism patient-parent trios – and the answers appear to be straightforward. Continue reading