Taking the Oath. I was naturalized as a United States citizen in Philadelphia today. This was a big step for me personally that started with my move to the US more than a decade ago. As an immigrant physician-scientist, I have lived through the most dynamic decade in child neurology, which is my chosen field of work. During this time, many previously unnamed conditions have been deciphered, genetically characterized, and moved towards targeted treatments such as gene therapies. With this as a background, let me summarize why I am excited to be a US citizen.
Monthly Archives: May 2025
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.
Orchestrating the synapse – a solo for Bassoon
Presynaptic. Over the last decade, there has been significant interest in understanding the role of synaptic genes in neurodevelopmental disorders and epilepsy. While we have made significant progress on conditions such as STXBP1– and SYNGAP1-related disorders, many synaptic genes remain uncharacterized. In a recent publication, we delineated the phenotypic range of the newest member of this group of genes: BSN, encoding the presynaptic protein, Bassoon. Here is how we deciphered the landscape of BSN-related disorders, integrating real-world data and biorepositories.
The Spliceosome Connection – RNU4-2 in neurodevelopmental disorders
An RNA world. Last week, a simple bar graph caught my attention and prompted me to write my first blog post in over a year. I came across a figure comparing the frequency of de novo variants in RNU4-2 to other genes causing neurodevelopmental disorders. The data suggested that the recently identified ReNU syndrome may be one of the most common genetic neurodevelopmental disorders with a high frequency of seizures. This led me to take a closer look at a group of conditions that have emerged over the last few years: disorders of spliceosome function, providing some interesting insight into the dynamics of gene discovery in the post-genomic era.