ArticleBrain : a journal of neurology2022
Assessing the landscape of STXBP1-related disorders in 534 individuals.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06555965 (STXBP1 and SYNGAP1 Related Disorders), which is not on this map. Cited by 70 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
STXBP1 and SYNGAP1 Related Disorders (RD) Natural History Study
Who cites it
70 citing papers in PubMed, 116 citations in OpenAlex.
- Associations of Cortical and Subcortical White Matter Morphometric Abnormalities With Clinical and Genetic Findings inNeurology. Genetics · 2026Article
- Single cell RNA-sequencing reveals neuron type-specific vulnerabilities in a model of STXBP1-related disorder.Molecular psychiatry · 2026Article
- Heterozygous Variants in LRP1 Cause a Neurodevelopmental Disorder With Congenital Heart Defects.American journal of medical genetics. Part A · 2026Article
- STXBP1 Variants Associated With Epilepsy With Variable Severity.CNS neuroscience & therapeutics · 2026Article
- Translatable electrophysiological and behavioral abnormalities in a humanized model of SYNGAP1-disorder.Molecular psychiatry · 2026Article
- Phenotypic diversity is caused by non-linear genetic interactions between two SNAREopathy genes.Molecular psychiatry · 2026Article
- CharacterizingmedRxiv : the preprint server for health sciences · 2026Article
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- Molecular and clinical spectrum of epilepsy-dyskinesia syndromes: a cross-sectional study of 609 patients.Brain : a journal of neurology · 2026Article
- Integrating rare and common variation in epilepsy genetics: from genetic architecture to penetrance and clinical expressivity.Frontiers in genetics · 2026Review
- ZDHHC5 interacts physically and functionally with DLG1 at primary cilia and regulates ciliary length and kidney morphology.Frontiers in cell and developmental biology · 2026Article
- Functional Analyses in Patient-Derived Neurons Establish Pathogenicity forHuman mutation · 2026Article
- Characterizing Key Correlates of Sleep Problems Across Rare Neurodevelopmental Genetic Disorders.Journal of autism and developmental disorders · 2025Article
- Evaluation, Diagnosis, and Treatment of Concomitant Movement Disorders in Genetic Epilepsies.Epilepsy currents · 2025Review
- Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.Nature genetics · 2025Article
- Article
- Visual Function Characteristics inJournal of clinical medicine · 2025Article
- Familial SYNGAP1 variants define the boundaries of a complex neurodevelopmental disorder with epilepsy.Epilepsia · 2025Article
- Neuron-targeted gene therapy rescues multiple phenotypes of STXBP1-related disorders in mice and is well tolerated in nonhuman primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
54 authors at 18 institutions in 10 countries.
Funding
Abstract
Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.