Water. Three years ago, on Rare Disease Day 2023, I published a blog post comparing phenotypes to water, existing in three phases: solid, liquid, and vapor. At the time, I was trying to make a simple point. Rare diseases are not defined by their first description, nor only by a checklist of features. They are moving targets. Here is what has changed since then.
Tag Archives: EMR genomics
The Long Arc of TBC1D24
Arc. Among the various synaptic disorders, TBC1D24 remains one of the more mysterious conditions. Although this genetic epilepsy was first described in 2010, the trajectory of symptoms over time has been poorly understood. In a recent publication, we reconstructed longitudinal seizure histories and developmental trajectories from electronic medical record data. What emerged was a disorder that dramatically changes shape over time. Here is what we found.
Predicting genetic epilepsies through EMR fingerprints
EMR. Clinical data on rare disease is not necessarily rare; it is our ability to unlock already existing data that is rare. Over the last decade, we have tried to understand the fingerprints that rare genetic epilepsies leave in the electronic medical record (EMR). In our flagship publication last year, we tried to push the boundary. Is EMR data, with all its strength and weaknesses, able to predict genetic diagnosis? Here is our journey through the hidden signals in large EMR datasets.
STXBP1 – here is what you need to know in 2023
STXBP1. Today is the first day of the 1st European STXBP1 Summit and Research Roundtable, held from May 16-18th in Milan, Italy. This meeting is bringing together voices from academia, industry, organizations, and family foundations to discuss the current state of research – spanning from preclinical efforts investigating mechanisms of disease to moving towards the clinic and the future therapeutic landscape. In 2023, it feels like an understatement to say that STXBP1 is on the map. In spirit of the ongoing momentum in the field, we wanted to refresh the gene page and outline three emerging frameworks to think about STXBP1.
Seizure prediction using real world data – a learning health system realized
Neonatal seizures. Neonatal seizures can lead to serious consequences for newborns, including long-term morbidity and mortality. In high-resource neonatal intensive care units, screening for seizures with CEEG has become commonplace and is considered standard of care. Accurate seizure prediction can help optimize the allocation of CEEG resources and improve care for critically ill neonates. In our recent study, we aimed to develop seizure prediction models using data extracted from standardized EEG reports. Here is a brief overview of our findings using real-world data to predict seizures in neonates.
The science of data visualization in epilepsy genetics
Language. In the recent years, there has been an emerging focus on the phenotypic characterization of genetic epilepsies and neurodevelopmental disorders. With a rise in large-scale studies leveraging massive and complex genetic and phenotypic datasets, understanding how we make sense of big data becomes critical. However, determining what are clinically meaningful findings and communicating the conclusions we make from these datasets remain a challenge. While we typically think about data in the scope of ‘n’s, probabilities, and p-values, there is understated value in the visualization of information. Here is a different way of how we think about scientific communication and how we can “make data speak in childhood epilepsies.”
Phenotypes are like water – Rare Disease Day 2023
Phases. Today is Rare Disease Day. I would like to use this opportunity to explain some of the phenotype science that is critical for rare diseases. In contrast to common disorders, rare diseases face an unusual challenge. Once identified, the overall rareness of these condition poses the question of where phenotypes begin and where they end. For rare genetic disorders, is the phenotype of the first individual identified with a rare disease characteristic, or is there a larger spectrum that we should be aware of? Enter the various approaches to phenotype science that aim to decipher the full depth of clinical features associated with rare diseases. In order to understand the various approaches to rare diseases phenotypes, I would like to suggest a somewhat unusual analogy: phenotypes are like water.
The genetics of FIRES and status epilepticus in 2023
FIRES. As a rare and severe epilepsy syndrome, febrile-infection related epilepsy syndrome (FIRES) is characterized by refractory status epilepticus (RSE) preceded by a febrile illness and often leads to prolonged hospitalizations, cognitive impairment, and intractable epilepsy. There are currently no clear causative etiologies identified in FIRES, and the underlying genetic architecture remains elusive. Here is a brief summary of our recent manuscript on the genetics of FIRES and refractory status epilepticus. This is what we learned about one of the most enigmatic conditions in child neurology.
Precision medicine in the absence of outcomes
EMR. Genomic data is increasingly available for large patient cohorts. In parallel, healthcare is increasingly digitized and large amounts of data can easily be extracted and analyzed at the click of a button. In principle, this should provide tremendous opportunities to understand how epilepsy care can be personalized based on genetic factors. However, we quickly run into challenges. Obtaining information on seizure frequencies, for example, requires manual chart review. Trying to understand how a person’s genetic makeup affects responses to anti-seizure medications is therefore not possible in large healthcare systems where related questions in other diseases can increasingly be answered. Here is a brief overview of how we can meaningfully engage with clinical data when outcomes are simply not available. Continue reading