Strides in STXBP1 Research in Aug and Sep

What was new in August & September of 2025?

An Indonesian group of researchers and physicians conducted a broad review of the scientific literature to identify the leading genetic causes of developmental and epileptic encephalopathies (DEEs). They found that five genes were strongly associated with DEE in infants, STXBP1, SLC1A2, CDKL5, SCN1A, and KCNT1. They further found that each of these genes was associated with a unique type of epilepsy, with STXBP1 being strongly associated with Ohtahara Syndrome. Variants in STXBP1 were also associated with West Syndrome and Dravet Syndrome but were not the dominant gene variants found in those epilepsies.

French doctors conducted a retrospective analysis of patients who had neonatal seizures with no identifiable brain abnormality, to better understand the outcome of such patients. The study followed 56 newborns who had epilepsy that started within the first month of life, didn’t respond to standard medications, and showed no abnormalities on brain MRI. Most of these cases were linked to genetic causes, especially variants in KCNQ2, STXBP1, and KCNT1. Despite having normal brain scans, nearly all children developed intellectual disabilities, and three-quarters had severe developmental challenges, including problems with movement, feeding, and communication. Only two children had typical development. The strongest early warning sign of poor outcomes was an abnormal neurological exam during the neonatal period. The study emphasizes that even when brain imaging looks normal, early signs and genetic testing are crucial for predicting long-term challenges and guiding healthcare.

A group of scientists and patient advocates reported on an anonymous, internet-based survey to assess the needs of DEE families. This study surveyed 134 family caregivers – mostly parents and some adult siblings – of individuals with DEEs such as Dravet syndrome, Lennox-Gastaut syndrome, and STXBP1-RD, to understand their preparedness for long-term care planning. The majority of individuals with DEE required constant supervision and assistance with basic daily tasks like bathing, dressing, and eating, due to seizures, intellectual disabilities, and other complex challenges. Despite these high care needs, over half of caregivers had not begun planning for medical, legal, or financial transitions into adulthood, and nearly 80% reported lacking access to adequate resources or guidance. Adult siblings often anticipated taking on future caregiving roles but felt excluded from current planning efforts. Families primarily turned to patient organizations, peer networks, and social media for support, while healthcare professionals, especially adult providers, were rarely seen as reliable sources of information. The findings of the survey highlight a significant gap in transition planning and underscore the need for better resources.

Two publications reported on visual problems associated with STXBP1-RD. The group led by Scott Demarest at Children’s Hospital Colorado looked to see how common and serious a vision problem called cortical visual impairment (CVI) is in children with one of four neurogenetic conditions, STXBP1, SLC6A1, Ring 14, and 8p-related disorders. CVI occurs when the brain has trouble processing visual information, even though the eyes themselves are healthy. The team found that nearly half of the kids studied had CVI, especially those with 8p-related disorders (54%) and STXBP1 (50%). Kids with CVI tended to have more severe developmental challenges, including difficulties with communication, motor skills, and daily living. The study also tested a new screening tool that helped doctors identify CVI more accurately. Early diagnosis of CVI is important so that children can receive the correct therapies and educational support. In another publication, a team from Poland looked at how vision is affected in children with STXBP1-RD. They examined 26 children and found that while their eyes were normal, many had significant functional vision issues. Most had farsightedness (hyperopia), nearly all had astigmatism, and over half had trouble with eye coordination and focusing (poor convergence and reduced accommodation). These problems make it harder for children to engage with their surroundings and develop social and motor skills and highlight the importance of early eye exams and corrective lenses. The group also suggested that CVI may play a role in visual problems as well.

An interesting article was published by researchers from India. The article explored how the STXBP1 protein could play a key role in treating dementia. Dementia is caused by a mix of problems in the brain, like a build-up or aggregation of harmful proteins such as amyloid-beta or tau protein in Alzheimer’s disease and frontotemporal dementia, or alpha-synuclein in Parkinson’s disease or Lewy body dementia. Neuroinflammation and damage to nerve connections can also lead to dementia. STXBP1 protein is well known to help neurons communicate by controlling the release of neurotransmitters, and a reduction of STXBP1 protein, as in STXBP1-RD, leads to dementia-like symptoms such as intellectual disability and motor problems. But there is evidence that the protein does much more: it affects how amyloid and tau proteins are processed, helps manage alpha-synuclein, and even influences brain inflammation and stress responses. Because it connects so many parts of dementia biology, therapies aimed at stabilizing or restoring STXBP1 protein in the brain could offer a new way to treat dementias caused by multiple diseases.