Adrenocorticotropic hormone (ACTH) is a hormone produced in the anterior, or front, pituitary gland in the brain. The function of ACTH is to regulate levels of the steroid hormone cortisol, which released from the adrenal gland. ACTH is also known as: adrenocorticotropic hormone.
Allele / Biallelic
An allele is a variant form of a gene. Some genes have a variety of different forms, which are located at the same position, or genetic locus, on a chromosome. Humans are called diploid organisms because they have two alleles at each genetic locus, with one allele inherited from each parent.
Apnoea is defined as no effective respiratory effort for ≥ 20 seconds or for > 10 seconds if associated with oxygen desaturation, cyanosis (turning blue) or pallor.
Pulmonary aspiration is the entry of material such as secretions, food or drink, or stomach contents from the gastrointestinal tract into lower respiratory tract, the portions of the respiratory system from the trachea to the lungs.
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk and with onset in infancy.
Cerebellar ataxia leads to a lack of muscle movement coordination caused by a dysfunction in a part of the brain called the cerebellum, which controls the timing and force of muscle movement. People with cerebellar ataxia have trouble balancing, walk in an uncoordinated and unsteady way, and find it difficult to carry out fine movements with the hands and arms. It can be caused by conditions that lead to brain damage such as genetic cerebellar disorders.
The corpus callosum is a thick band of nerve fibres that divides the cerebral cortex lobes into left and right hemispheres. It connects the left and right sides of the brain allowing for communication between both hemispheres. The corpus callosum transfers motor, sensory, and cognitive information between the brain hemispheres.
In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure.
Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division.
Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labelled the “p arm.” The long arm of the chromosome is labelled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes. The WWOX gene is located on the long arm of Chromosome 16.
Clonus is a series of involuntary, rhythmic, muscular contractions and relaxations. Clonus is a sign of certain neurological conditions, particularly associated with upper motor neuron lesions involving descending motor pathways, and in many cases is, accompanied by spasticity (another form of hyperexcitability). Clonus in the ankles of WWOX children may be noticed when putting pressure on the feet of their soles. 8 to 10 beats may be present a normal newborn, but generally disappears by 2 months of age.
A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighbouring genes. The deleted DNA may alter the function of the resulting protein(s).
DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). Mitochondria are structures within cells that convert the energy from food into a form that cells can use.
The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences.
DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.
An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.
An electroretinography (ERG) test, also known as an electroretinogram, measures the electrical response of the light-sensitive cells in the eyes. These cells are known as rods and cones. They form part of the back of the eye known as the retina.
Enzymes are biological molecules (typically proteins) that speed up the rate of most chemical reactions that take place within our cells. They are vital for life and serve a wide range of important functions in the body, such as aiding in digestion and metabolism.
Epileptic encephalopathies refer to a group of disorders in which the unremitting epileptic activity contributes to severe cognitive and behavioural impairments above and beyond what might be expected from the underlying pathology alone, and these can worsen over time leading to progressive cerebral dysfunction.
Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain.
A gene is the basic physical and functional unit of heredity. Genes are made up of DNA. Some genes act as instructions to make molecules called proteins. However, many genes do not code for proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project estimated that humans have between 20,000 and 25,000 genes.
Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.
Scientists keep track of genes by giving them unique names. Because gene names can be long, genes are also assigned symbols, which are short combinations of letters (and sometimes numbers) that represent an abbreviated version of the gene name. In our case, a gene on chromosome 16 that encodes a protein called WW domain containing oxidoreductase is known as WWOX.
Hyperreflexia is defined as overactive or overresponsive reflexes. Examples of this can include twitching or spastic tendencies.
Hypokinesia refers to decreased bodily movement. It is a movement disorder which is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia.
Infantile Spasms / West Syndrome
West syndrome is a severe epilepsy syndrome composed of the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern termed hypsarrhythmia, and mental retardation. The International League Against Epilepsy's (ILAE) revised classification and terminology of seizures and epilepsies, published in 2010, designates West syndrome as an electroclinical syndrome with onset in infancy, and epileptic spasms as a type of seizure. West syndrome is an age-dependent expression of a damaged brain, and most patients with infantile spasms have some degree of developmental delay. The term infantile spasm has been used to describe the seizure type, the epilepsy syndrome, or both. The seizures (or spasms) make muscles in the arms and legs stiff and bend the child’s head forward. They look very much like a startle.
Metabolism is the term for a set of chemical reactions that occur in the cells of living organisms to sustain life.
Microcephaly is a medical condition in which the brain does not develop properly resulting in a smaller than normal head. In the case of children affected by WWOX mutations, it may develop in the first few years of life.
A genetic alteration in which a single base pair substitution alters the genetic code in a way that produces an amino acid that is different from the usual amino acid at that position. Some missense variants (or mutations) will alter the function of the protein. This amino acid substitution may have no effect, or it may render the protein nonfunctional.
Magnetic resonance imaging is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body.
Multifocal seizures arise from multiple locations and can affect both hemispheres of the brain.
A DNA mutation means that the sequence of genetic code in or in part by a change in the DNA sequence away from the normal sequence. In other words, the sequence of code which instructs cells to produce a certain protein or enzyme lacks some information or contains invalid instructions which results in a defective (mutant) protein being produced or in some cases nothing at all. The body has a surveillance system which looks out for mutant proteins and will typically destroy them as they could do harm. Consequently, our children lack the WWOX enzyme which results in SCAR12 or WOREE syndrome.
Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's wires) to insulate them and increase the rate at which information (encoded as electrical impulses) is passed along the axon. Developmental delay is the most common clinical correlate of delayed myelination.
A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.
A phenotype is an individual's observable traits, such as height, eye colour, and blood type. Or in the case of genetic diseases, the result (symptoms) of the genetic mutation the patient has. The genetic contribution to the phenotype is called the genotype.
Pneumonia is an inflammatory condition of the lungs affecting primarily the small air sacs known as alveoli. Pneumonia is usually caused by infection with viruses or bacteria. In the case of children with WOREE syndrome, aspiration pneumonia is caused due to material from the stomach or mouth entering the lungs. Due to the level of impairment of children with WOREE syndrome, pneumonia is extremely serious and the leading cause of mortality. All practical care should be taken to keep children as protected as possible from sources of infection and aspiration from feeding.
Prednisone is a corticosteroid. It prevents the release of substances in the body that cause inflammation. It also suppresses the immune system. Prednisone is used as an anti-inflammatory or an immunosuppressant medication.
Another term for the respiratory system which includes the lungs.
Drug-resistant epilepsy, also known as refractory epilepsy or pharmacoresistant epilepsy, is defined as failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs to achieve sustained seizure freedom.
Scoliosis is a sideways curving and turning of the bones of a child's spine.
Tonic Clonic Seizure
Tonic–clonic seizures (previously called grand mal seizures) can result from either primary or secondary generalized seizures. Tonic–clonic seizures are characterized by clonic or myoclonic movements evolving to tonic muscle extension of the limb and trunk muscles followed by clonic contraction. Tonic–clonic seizures may be accompanied by significant morbidity and mortality. Brain injury and malformations, genetic disorders, inborn errors of metabolism and neurodegenerative disorders may be associated with tonic–clonic seizures.
Tumour Suppressor Gene
A tumour suppressor gene is a gene that regulates a cell during cell division and replication to prevent cells growing which can result cancer.
Vigabatrin, brand name Sabril, is a medication used to treat epilepsy. It became available as a generic medication in 2019. It works by inhibiting the breakdown of γ-aminobutyric acid. It is also known as γ-vinyl-GABA, and is a structural analogue of GABA, but does not bind to GABA receptors.