Glossary

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Absence Seizures - Formerly known as petit mal seizures, they are a form of seizure that is described as brief periods of time (roughly 10-20 seconds) where the person stops activity and may appear as if having a vacant stare or daydreaming. Sometimes the eyes may also turn upward or flutter. In rare instances (in atypical absence seizures), a person may also rub their fingers or hand together, eyes may blink, lips may smack or have jerking movements, or make chewing movements with their mouth; are described lasting 5 to 30 seconds. Resource: Epilepsy Foundation (Absence Seizures, symptoms and risks | Epilepsy Foundation) and (Atypical Absence Seizures | Epilepsy Foundation)

Antiepileptic Drugs (AED) - Medications used to treat epilepsy by suppressing seizures. Also known as anticonvulsants. Resource: Epilepsy Foundation (Summary of Antiepileptic Drugs | Epilepsy Foundation)

Antisense oligonucleotides (ASO) - A type of genetic therapy that alters the expression of mRNA in a cell. 

Ataxia - Differences in the coordination of movements due to decreased muscle control as a result of differences in a part of the brain called the cerebellum or its connections. Can impact walking and balance, hand coordination, speech and swallowing, and eye movements. Ataxia is a feature of many conditions. ~40% of individuals with STXBP1-related conditions experience ataxia, but this varies from patient to patient.

Atonic Seizure - Also known as drop attack or drop seizures, they are a form of seizure where the person loses muscle tone where the head or body will go limp. They typically last less than 15 seconds. Resource: Epilepsy Foundation (Atonic Seizures | Epilepsy Foundation)

Autism - A developmental disorder affecting communication and behavior. It is a disorder which is screened for and diagnosed by a licensed healthcare provider. It is also known as Autism Spectrum Disorder (ASD). Resource: NIMH / NIH

Autosomal Dominant - Refers to a genetic condition that can manifest due to a variant in one of the two copies of the implicated gene. Autosomal indicates that a gene is located on a non-sex chromosome (chromosomes 1-22). STXBP1-related disorders can sometimes be inherited in an autosomal dominant manner.

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Bruxism - Involuntary clenching, grinding, and/or gnashing of the teeth that occurs when someone is not chewing. This typically happens subconsciously or without the individuals' awareness, either during waking or sleeping hours. For people with STXBP1-related disorders, this is more common during wakefulness rather than during sleep. ~80% of people with STXBP1-related disorders experience bruxism. (Resasadeh et al., 2019)

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Cerebral Palsy (CP) - A group of neurologic disorders caused by damage or abnormalities in the brain that affect movement, balance, and posture. Resource: NINDS/NIH

Chromosome - A structure in which genetic material is organized. In humans, there are 23 pairs of chromosomes and are designated by numbers 1-22 and the sex chromosomes, X and Y.

Citizen Health (formerly Ciitizen) - Citizen Health is a digital health platform that empowers patients to collect, organize, and share their medical records securely. The service enables individuals to have a comprehensive view of their health information, which can be easily accessed and shared with healthcare providers, researchers, or family members as needed. For individuals with STXBP1-related disorders, Citizen Health can be particularly beneficial. It allows families to consolidate medical records from various sources, ensuring that all pertinent information, such as genetic test results, treatment histories, and developmental assessments, is readily available. This can facilitate better coordination of care, participation in research studies, and access to clinical trials.

Clinical Diagnosis - A clinical diagnosis is determined by a healthcare provider based on observation and examination of symptoms, without genetic testing results to confirm the diagnosis (whether results were not informative or testing has not been done). A diagnosis of an STXBP1-related disorder is unlikely without supporting genetic testing results.

Clinical Trials - A type of research study that evaluates a test or treatment in people.

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Deletion Mutation - It is a type of mutation that removes genetic material from a gene, including deletion of the entire gene.

Deoxyribonucleic acid (DNA) - It is a basic unit for the storage of genetic information. It includes one of four nucleic acids: adenine (A), cytosine ( C), guanine (G), and thymine (T). The nucleic acids form chemical bonds with specific partners (adenine pairs with thymine; cytosine pairs with guanine) which are known as a “base pair”. DNA includes segments that are used for protein production (or known as coding DNA) and not used for genes (non-coding DNA).  DNA can be transcribed into mRNA (see “mRNA” definition). 

De novo - New mutation; disease has not been down from generation to generation.

Developmental Delay - Used to describe instances when a child is not reaching developmental milestones at the expected times compared to peers. Children with STXBP1-related disorders can experience developmental delays, which may affect their motor skills, speech, and cognitive abilities.

Disease Mechanism - The disease mechanism refers to the underlying process that leads to a disorder. For STXBP1-related disorders, this involves how changes in the STXBP1 gene affect the function of neurons and lead to symptoms.

Duplication Mutation - It is a type of mutation that adds genetic material from a gene.

Dystonia - Differences in muscle tone resulting in involuntary muscular contractions, or spasms, that cause repetitive movements or abnormal postures. These muscle contractions can be sustained or intermittent and may affect any part of the body, including the neck, face, arms, and legs. In individuals with STXBP1-related disorders, dystonia can significantly impact their ability to move smoothly and coordinate their actions, leading to challenges with activities like walking, writing, or speaking. The severity and specific symptoms of dystonia can vary widely among those with STXBP1-related disorders.

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Early Intervention Services - Publicly funded services that are available to babies and young children with developmental delays and disabilities and their families. These services may include speech therapy, physical therapy, and other types of services based on the needs of the child and family. Programs are available in every U.S. state and territory and services are provided for free or at reduced cost for any child who is eligible. (CDC) https://www.cdc.gov/ncbddd/actearly/parents/states.html#textlinks for each state's program and their contact info

Electroencephalogram (EEG): A diagnostic test of brain electrical activity.

Electrical status epilepticus of sleep (ESES) - A rare and serious syndrome that is characterized by a particular EEG pattern seen during sleep. It is also known as epileptic encephalopathy with continuous spike and wave during sleep (CSWS). Resource: Epilepsy Foundation (Epileptic Encephalopathy with Continuous Spike and Wave During Sleep (CSWS) | Epilepsy Foundation)

Encephalopathy - A term used to describe a disease of the brain.

Epilepsy - A neurological disorder characterized by recurrent seizures and affects the nervous system.

Epilepsy Panel - A genetic test that analyzes many genes associated with epilepsy with one test.

European Medicines Agency (EMA) - It is a decentralized agency for the European Union (EU) that is responsible for the scientific evaluation, supervising and safety monitoring the safety of medicines used in the EU. Resource: European Medicines Agency | (europa.eu)

Exon - Segment of DNA that codes for a gene or part of a gene.

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Febrile Seizure - A seizure associated with a high fever in children. Resource: Epilepsy Foundation (Febrile Seizures | Epilepsy Foundation)

Food Drug and Administration (FDA) - The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. Resource: U.S. Food and Drug Administration (fda.gov)

Focal Seizures - Also known as partial seizures. Refers to a seizure that starts in one area or network of brain cells on one side of the brain. They can occur with or without loss of consciousness. Some times these seizures are also categorized as: simple (Focal Aware Seizures), complex (Focal Impaired Awareness Seizures), and secondary generalized seizures (Focal to Bilateral Tonic Clonic Seizures). Resources: Epilepsy Foundation (Focal Onset Aware Seizures | Epilepsy Foundation), (Focal Onset Impaired Awareness Seizures | Epilepsy Foundation), and (Focal to Bilateral Tonic-clonic Seizures | Epilepsy Foundation)

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Gene - It is a basic unit of heredity and made up of DNA; it can act as genetic instructions to produce proteins. Resource: NIH/Medline Plus - Genetics (What is a gene?: MedlinePlus Genetics)

Genome - A complete set of genetic material of an organism. This includes pairs of 23 chromosomes in the nucleus of a cell and mitochondrial DNA found within the mitochondria of the cell. Resource: NIH/National Genome Research Institute (https://www.genome.gov/genetics-glossary/Genome) 

Genetic Disorder - A disease that is a result of a change to one or more genes that alters the production of protein that makes it non-functional or missing. Resource: NIH/Medline Plus - Genetics (Genetic Disorders: MedlinePlus)

Genetic Variant / Pathogenic Variant - A change in the DNA sequence of a gene that is known to be associated with genetic condition or disease. Formerly referred to as "pathogenic mutation," but this term has fallen out of favor.

Gene Variant - It is a mutation in a gene that can change the protein produced which may cause a genetic disorder.

Global Developmental Delay - Significant delays in multiple areas of development in children under the age of five. These areas can include motor skills, speech and language, cognitive abilities, and social skills. Children with global developmental delay often show slower progress in reaching milestones like walking, talking, and learning compared to their peers.

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Haploinsufficiency - Chromosomes are arranged in pairs and there are two copies of each gene. For certain genes, both copies are needed to produce a protein. Haploinsufficiency occurs when one of the two genes is non-functional or deleted, and the amount of protein produced is not sufficient for normal functioning.

Hypertonia - Increased muscle tone, often resulting in stiff muscles, especially in the arms, legs, and neck

Hypotonia - A condition described as having low muscle tone. Resource: NIH/NINDS (Hypotonia Information Page | National Institute of Neurological Disorders and Stroke (nih.gov))

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ICD-10 - this is an acronym for International Classification of Diseases, Tenth Revision. It is a method to classify medical conditions, diseases, and procedures which is used in the healthcare setting. (https://www.cdc.gov/nchs/icd/icd-10-cm/index.html)
Incidence - It is a measurement describing the number of events (eg. number of individuals diagnosed with STXBP1) within a defined period of time.

Induced pluripotent stem cells (iPSCs) - Cells collected from the body (ie. skin) that are engineered into being pluripotent (or capable of being changed into other types of cells like neurons) through a specialized laboratory technique. They have been useful in studying biological processes and in drug development.

Infantile Spasms - Also known as West Syndrome. A type of seizure that usually presents with brief episodes of body stiffening and bending forward or backward of the arms, legs, and head (sometimes referred to as “jackknife seizures” or “flexor spasms”). Episodes are brief and often in clusters. Onset usually happens within the first year of life and stops around 4 years of age. Resource: Epilepsy Foundation (Treatment for Infantile Spasms | Epilepsy Foundation)

Intellectual Disability - A developmental disability characterized by defecits in areas responsible for learning, problem solving, adaptive skills development, and independence, generally with onset prior to 18 years of age. Individuals with STXBP1-related disorders may also be diagnosed with intellectual disability.

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Lennox-Gastaut Syndrome (LGS) - Resource: Epilepsy Foundation (Case Study on Lennox-Gastaut Syndrome | Epilepsy Foundation)

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Magnetic Resonance Imaging (MRI) - Medical imaging test that uses magnets and radio waves to create detailed images of the body's internal structures including organs, bones, muscles, and blood vessels. It is often used to examine the brain in individuals with STXBP1-related disorders to look for abnormalities.

MicroRNA (miRNA) - a small, non-coding RNA molecule that plays a crucial role in regulating gene expression. It works by binding to messenger RNA (mRNA) and preventing it from being translated into proteins or by promoting its degradation. This regulation is essential for various cellular processes, including development, differentiation, and response to stress. In the context of STXBP1-related disorders, alterations in microRNA function can impact the expression of genes involved in brain development and function, potentially contributing to the symptoms observed in these conditions. Research into microRNA may offer insights into new therapeutic approaches for managing STXBP1-related disorders.

Missense mutation - A type of mutation where a base pair (see “DNA” definition) is changed and it changes what is translated from DNA to mRNA and then final protein.

Mosaicism - Mosaicism describes the presence of a genetic variant in only some of the body's cells, resulting in a mixture of cells with typical DNA and cells with the genetic variant within the same cell types. In the case of somatic mosaicism, the genetic variant is present in some of the cells of the body that are not involved in reproduction. Depending on the level of mosaicism, or what proportion of cells contain the genetic variant, this can lead to variability in symptoms. Gonadal mosaicism, also known as germline mosaicism, occurs when some of a person's reproductive cells (sperm or eggs) carry a genetic variant that is not present in the rest of the body's cells. This means that a parent with gonadal mosaicism can pass on a genetic variant to their children even if the variant is not detected in their blood or other tissues. Gonadal mosaicism cannot be reliably or easily tested for, thus cannot be ruled out for partners of one child with a rare autosomal dominant condition like STXBP1-related disorders. For the purposes of family planning, it would definitely be important to discuss this with a healthcare provider who can provide appropriate resources and education about options for families who may be concerned about gonadal mosacism.

Mutation (genetic) - The term formerly used to refer to a genetic change. The proper terminology now is "genetic variant," but this word may still be seen in the literature.

Myoclonic seizure - Characterized by brief and rapid jerking movements, usually involving both sides of the body at the same time. Resource: Epilepsy Foundation

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N of 1 - N of 1 therapies are medicines developed to treat an individual patient. We encourage families who pursue N of 1 therapies to share data, which can include effectiveness, side effects, and protocol, back with the community.
National Organization for Rare Disorders (NORD) -  A non-profit patient advocacy organization representing those with rare diseases and the groups that support them. Resource: NORD (https://rarediseases.org/) 

Neonatal Seizures - Sudden, excessive bursts of electrical activity in a newborn's brain that can be a sign of a brain condition or injury. Neonatal, or newborn, refers to the first 4 weeks of life in a full-term infant and up to 44 weeks from cenception for premature infants. STXBP1-related disorders can present with neonatal seizures as an early symptom.

Neurons - Neurons, or nerve cells, send and receive messages between the brain and the body. Genetic variants in the STXBP1 gene can affect the ability of neurons to communicate properly, leading to symptoms of STXBP1-related disorders.

Neurotransmitter - It is a chemical substance that acts as a messenger between neurons. It is released at one end of a neuron (known as the axon terminal) from synaptic vesicles into a space called the synaptic cleft and received by a receptor of another neuron (known as the dendrite). There are many different types of neurotransmitters and neural pathways that impact functions throughout the body. 

Nonsense mutation - A type of mutation that results in the premature stop codon which results in an incomplete protein. Resource: NIH/NHGRI (https://www.genome.gov/genetics-glossary/Nonsense-Mutation) 

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Occupational Therapy - Intervention aimed at helping individuals perform daily activities independently and improve their quality of life. For people with STXBP1-related disorders, occupational therapy can assist with motor skills, self-care, and other functional abilities.

Ohtahara syndrome - A rare seizure disorder seen in infants that is characterized by tonic seizures, motor differences, and intellectual disability, and developmental delays. Is sometimes referred to as early infantile epileptic encephalopathy (EIEE). This condition has been linked to some genetic variants in the STXBP1 gene, but not all. Ohtahara syndrome can be linked to genetic variants in genes other than STXBP1 as well.

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Pathology - Pathology is the study of diseases, including their causes, processes, development, and consequences. It involves examining tissues, organs, bodily fluids, and autopsies to understand the nature and mechanisms of diseases. Pathologists use various techniques, such as microscopy and molecular analysis, to diagnose diseases and understand their effects on the body. In the context of STXBP1-related disorders, pathology focuses on understanding how genetic variants in the STXBP1 gene lead to neurological symptoms such as seizures, developmental delays, and cognitive impairments. By studying the underlying pathological mechanisms, researchers and healthcare providers can develop more effective diagnostic tools and treatments to manage and potentially mitigate the effects of these disorders.

Phenotype - Phenotype refers to the observable physical characteristics and traits of an individual that result from the interaction of their genetic makeup with the environment. These characteristics can include physical appearance, behavior, development, and biochemical properties. In the context of STXBP1-related disorders, the phenotype includes the specific symptoms and features associated with the condition, such as seizures, developmental delays, cognitive impairments, and motor difficulties. The phenotype can vary widely among individuals with the same genetic variant, influenced by factors such as other genetic elements and environmental conditions. Understanding the phenotype helps healthcare providers diagnose the disorder and tailor treatment plans to the individual’s specific needs.

Physical Therapy - Physical therapy is a therapeutic intervention focused on improving and restoring physical function and mobility. It helps individuals who have movement difficulties, pain, or physical impairments due to injury, illness, or genetic conditions. For individuals with STXBP1-related disorders, physical therapy can address issues such as muscle weakness, coordination problems, balance difficulties, and delays in motor skills development. A physical therapist works with the individual to create a personalized plan that may include exercises, stretching, strength training, and activities to enhance mobility and physical function. The goal is to improve the individual's ability to perform daily activities and enhance their overall quality of life.

Precision Medicine - Also known as personalized medicine; it is a concept of tailoring prevention and treatments to an individual to take into account differences in genes, environment and lifestyle. Resource: NIH/Medline Plus - Genetics (What is precision medicine?: MedlinePlus Genetics)

Prevalence - A measurement of the number of people affected (eg. number of people diagnosed with STXBP1) at one particular point in time.

Protein Truncating Variant - A type of genetic variant that causes the production of a shortened, incomplete protein. This can cause the protein to lose it's ability to carry out important functions, or in some cases, interfere with other molecular functions and cause disruptions that can cause disease.

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Rare Epilepsy Network (REN) - a volunteer network that welcomes all rare epilepsy organizations to come together around research efforts where our collective efforts will improve the lives lived of our individual constituents. REN includes rare epilepsy organizations and broad epilepsy stakeholders committed to this common mission. More.

RARE-X - RARE-X is a nonprofit organization dedicated to accelerating the discovery of treatments for rare diseases by fostering data collection and sharing. The organization provides a platform for patients, families, researchers, and clinicians to contribute and access valuable data about rare conditions. By centralizing and standardizing data, RARE-X aims to enhance collaboration, drive research, and support the development of new therapies for rare diseases. For families and individuals affected by STXBP1-related disorders, RARE-X offers resources and tools to share their health information securely. This collective data can help researchers identify patterns, understand disease mechanisms, and develop targeted treatments. RARE-X emphasizes patient privacy and consent, ensuring that participants have control over how their data is used.

Recurrence Risk - Recurrence risk refers to the likelihood that a genetic disorder or condition will occur again in a family. For families with a child affected by an STXBP1-related disorder, understanding the recurrence risk is important for future family planning. This risk depends on several factors, including whether the genetic variant is inherited or occurred de novo (newly in the affected child). A genetic counselor can provide a more personalized recurrence risk, taking a family's complete history into account, but generally, if a variant is de novo, the recurrence risk for future children is generally low but not zero, due to the possibility of gonadal mosaicism in one of the parents. Genetic counseling can also help families understand their specific recurrence risk and discuss options for future pregnancies and family planning.

Refractory Seizures - Seizures that do not respond well or at all to therapy/treatment with anti-epileptic medication. These types of seizures have been observed in about one-quarter of STXBP1 cases. (MedLine Plus)

Responsive neurostimulation (RNS) - A medical device that is implanted into the skull and may be considered as a treatment option for management of epileptic seizures when medications are not effective. The battery-powered device is connected to one or two electrodes. When an electrode detects abnormal electrical activity, the device responds with an electric shock to prevent the development of an epileptic seizure. This device is FDA approved in the United States.

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Simons Searchlight - Simons Searchlight is a research initiative that collects and shares data to advance the understanding of rare genetic conditions, including STXBP1-related disorders. It aims to accelerate research and improve the lives of individuals and families affected by these conditions. Simons Searchlight works by gathering detailed information from participants, including medical history, genetic test results, and developmental assessments. This data is made available to researchers worldwide, promoting collaboration and discovery. Participants also receive updates on the latest research findings and potential clinical trials. For families dealing with STXBP1-related disorders, Simons Searchlight provides an opportunity to contribute to a larger body of knowledge that can lead to better diagnostic tools, treatments, and support resources. The initiative emphasizes patient privacy and informed consent, ensuring that participants' data is handled securely and ethically.

SINEUPs:

Small Molecule Therapy - Small molecule therapy involves the use of low molecular weight compounds that can easily enter cells to modify biological processes. These therapies are designed to target specific proteins or pathways within cells to treat various diseases. In the context of STXBP1-related disorders, small molecule therapies aim to correct or compensate for the effects of genetic variants in the STXBP1 gene. By targeting the underlying mechanisms of the disorder, these therapies have the potential to improve symptoms such as seizures and developmental delays. Research is ongoing to identify and develop small molecule therapies that could be effective for individuals with STXBP1-related disorders.

SNARE proteins - In the brain, it is a group of proteins that create a structure known as the “snare complex” that is involved in the release of neurotransmitters into the synaptic cleft.

Socialization Therapy - Socialization therapy is a type of intervention designed to help individuals improve their social skills and interactions with others. It focuses on teaching and reinforcing behaviors that facilitate effective communication, understanding social cues, building relationships, and participating in social activities. For individuals with STXBP1-related disorders, socialization therapy can be particularly beneficial in addressing challenges related to social interaction and communication, enhancing their ability to engage with peers and caregivers in meaningful ways. This therapy is often tailored to the individual's specific needs and can involve activities, role-playing, and structured interactions guided by a therapist or trained professional.

Spasticity - A term used to refer to stiff or rigid muscles. This term may also be described as tightness or increased muscle tone. This stiffness or increased muscle tone can result in stronger or exaggerated reflexes and can interfere with walking, movement, and speech.

Speech Therapy - Speech therapy is a therapeutic intervention aimed at improving communication skills. It helps individuals with speech, language, and communication difficulties to develop and enhance their ability to speak, understand, express, and interact effectively. For individuals with STXBP1-related disorders, speech therapy can address issues such as delayed speech development, difficulty with articulation, understanding language, and using language socially. A speech therapist works with the individual to create a personalized plan that may include exercises, activities, and the use of assistive technology to support communication. The goal is to help the individual communicate more effectively and improve their overall quality of life.

Sudden Unexpected Death in Someone with Epilepsy (SUDEP) - It is an unexplained death in someone who has epilepsy. It is estimated that more than 1 in 1,000 individuals with epilepsy will die from SUDEP each year and it is the leading cause of death for those with uncontrolled seizures. Resource: Epilepsy Foundation

Synapse - It is the junction of where electrical or chemical signals are transmitted between two neurons. It is made of the presynaptic membrane (where neurotransmitters are released), the synaptic cleft, and the postsynaptic membrane (where neurotransmitters are received).

Syntaxin Binding Protein - 1 (STXBP1) - It is a protein necessary for the release of neurotransmitters

STXBP1-related Disorders - STXBP1 is not the name of a medical condition but rather is the name of the gene that is affected. When a disorder is traced back to a pathogenic variant in the STXBP1 gene, it is called an STXBP1-related disorder. More.

STXBP1 Investigator & Family Meeting (SIFM) - the former name of the annual conference produced by the STXBP1 Foundation. Our goal has been to hold an in-person, physical meeting every other year and a webinar series held virtually the years in-between. More.

STXBP1 Summit+ - the name of our current annual conference that combines our STXBP1 disorders families plus researchers, clinicians, and industry experts. More.

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Tonic-Clonic Seizure - Formerly known as Gran Mal seizures. Resource: Epilepsy Foundation (Tonic-Clonic Seizures | Epilepsy Foundation)

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Vagus nerve stimulation (VNS) - Vagus nerve stimulation (VNS) is a treatment method that involves a device that is implanted in the chest that sends electrical impulses to the brain to reduce seizures to treat epilepsy. It may be considered for individuals with STXBP1-related disorders if medications are not effective.

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West syndrome - West syndrome, also known as infantile spasms, is a rare and severe epilepsy syndrome that typically begins in infancy. It is characterized by a specific type of seizure known as infantile spasms, which involves sudden, brief body stiffening and bending movements. These seizures often occur in clusters and are commonly accompanied by a distinct brain wave pattern called hypsarrhythmia on an electroencephalogram (EEG). Children with West syndrome may also experience developmental regression, where they lose previously acquired skills, as well as significant developmental delays. The syndrome can be caused by a variety of underlying conditions, including genetic disorders such as STXBP1-related disorders.

Whole Exome Sequencing - A type of genetic testing that identifies the sequences of DNA from regions of the genome that code for proteins.

Whole Genome Sequencing - A type of genetic testing that sequences the entire genome

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4-Phenylbutyrate (4PB) - A chemical compound used to treat urea cycle disorders, which is another rare disease unrelated to STXBP1 disorders. Research studies has shown the compound may be useful in treating STXBP1 disorders but it needs to be further evaluated in humans through clinical trials.