114-477: Angelman syndrome ( AS ) is a genetic disorder that mainly affects the nervous system . Symptoms include a small head and a specific facial appearance, severe intellectual disability , developmental disability , limited to no functional speech, balance and movement problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become noticeable by one year of age. Angelman syndrome
228-416: A chromosome abnormality . Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome . The mutation responsible can occur spontaneously before embryonic development (a de novo mutation), or it can be inherited from two parents who are carriers of a faulty gene ( autosomal recessive inheritance) or from
342-417: A hominid was in the fossil species Paranthropus robustus , with over a third of individuals displaying amelogenesis imperfecta . EDAR ( EDAR hypohidrotic ectodermal dysplasia ) Electroencephalography Electroencephalography ( EEG ) is a method to record an electrogram of the spontaneous electrical activity of the brain . The biosignals detected by EEG have been shown to represent
456-509: A seizure is occurring. This is known as an ictal recording, as opposed to an interictal recording, which refers to the EEG recording between seizures. To obtain an ictal recording, a prolonged EEG is typically performed accompanied by a time-synchronized video and audio recording. This can be done either as an outpatient (at home) or during a hospital admission, preferably to an Epilepsy Monitoring Unit (EMU) with nurses and other personnel trained in
570-472: A voltmeter . Recording these voltages over time gives us the EEG. The electric potential generated by an individual neuron is far too small to be picked up by EEG or MEG. EEG activity therefore always reflects the summation of the synchronous activity of thousands or millions of neurons that have similar spatial orientation. If the cells do not have similar spatial orientation, their ions do not line up and create waves to be detected. Pyramidal neurons of
684-468: A Boy with a Puppet. The boy's laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children. It was not a name that pleased all parents but it served as a means of combining the three little patients into a single group. Later the name was changed to Angelman syndrome. This article was published in 1965 and after some initial interest lay almost forgotten until
798-445: A child affected by the disorder. Examples of this type of disorder are albinism , medium-chain acyl-CoA dehydrogenase deficiency , cystic fibrosis , sickle cell disease , Tay–Sachs disease , Niemann–Pick disease , spinal muscular atrophy , and Roberts syndrome . Certain other phenotypes, such as wet versus dry earwax , are also determined in an autosomal recessive fashion. Some autosomal recessive disorders are common because, in
912-408: A cohort of 163 individuals with AS, ranitidine was shown to be the most frequently prescribed medication for treating gastroesophageal reflux disease (GERD). Early intervention with physiotherapy is sometimes used to encourage joint mobility and prevent stiffening of the joints. Occupational therapists can contribute to the development and augmentation of non-verbal communication skills by addressing
1026-705: A combined EEG/MEG (EMEG) approach has been investigated for the purpose of source reconstruction in epilepsy diagnosis. EEG has also been combined with positron emission tomography . This provides the advantage of allowing researchers to see what EEG signals are associated with different drug actions in the brain. Recent studies using machine learning techniques such as neural networks with statistical temporal features extracted from frontal lobe EEG brainwave data has shown high levels of success in classifying mental states (Relaxed, Neutral, Concentrating), mental emotional states (Negative, Neutral, Positive) and thalamocortical dysrhythmia . The brain's electrical charge
1140-577: A female in terms of disease severity. The chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an X-linked dominant disorder will all be unaffected (since they receive their father's Y chromosome), but his daughters will all inherit the condition. A woman with an X-linked dominant disorder has a 50% chance of having an affected foetus with each pregnancy, although in cases such as incontinentia pigmenti, only female offspring are generally viable. X-linked recessive conditions are also caused by mutations in genes on
1254-467: A first-line method of diagnosis for tumors , stroke , and other focal brain disorders, but this use has decreased with the advent of high-resolution anatomical imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT). Despite its limited spatial resolution, EEG continues to be a valuable tool for research and diagnosis. It is one of the few mobile techniques available and offers millisecond-range temporal resolution, which
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#17327805617201368-447: A gene into the potentially trillions of cells that carry the defective copy. Finding an answer to this has been a roadblock between understanding the genetic disorder and correcting the genetic disorder. Around 1 in 50 people are affected by a known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder . Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to
1482-418: A genetic disorder rests on the inheritance of genetic material. With an in depth family history , it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth , or contemplate termination . Prenatal diagnosis can detect
1596-474: A greater degree of self-care are possible among the least profoundly affected. Walking and the use of simple sign language may be beyond the reach of the more profoundly affected. Early and continued participation in physical, occupational (related to the development of fine-motor control skills), and communication (speech) therapies are believed to significantly improve the prognosis (in the areas of cognition and communication) of individuals affected by AS. Further,
1710-619: A hereditary disease is an acquired disease . Most cancers , although they involve genetic mutations to a small proportion of cells in the body, are acquired diseases. Some cancer syndromes , however, such as BRCA mutations , are hereditary genetic disorders. A single-gene disorder (or monogenic disorder ) is the result of a single mutated gene. Single-gene disorders can be passed on to subsequent generations in several ways. Genomic imprinting and uniparental disomy , however, may affect inheritance patterns. The divisions between recessive and dominant types are not "hard and fast", although
1824-483: A knife or spoon and fork, and can learn to perform simple household tasks. Particular problems which have arisen in adults are a tendency to obesity (more in females), and worsening of scoliosis if it is present. The affectionate nature may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable. People with Angelman syndrome appear to have a reduced but near-normal life expectancy, dying on average 10 to 15 years earlier than
1938-636: A known single-gene disorder, while around 1 in 263 are affected by a chromosomal disorder . Around 65% of people have some kind of health problem as a result of congenital genetic mutations. Due to the significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as " rare " (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves. Genetic disorders are present before birth, and some genetic disorders produce birth defects , but birth defects can also be developmental rather than hereditary . The opposite of
2052-444: A longer duration in the epilepsy monitoring unit (EMU) or at home with an ambulatory EEG. In addition, there are activating maneuvers such as photic stimulation, hyperventilation and sleep deprivation that can increase the diagnostic yield of the EEG. At times, a routine EEG is not sufficient to establish the diagnosis or determine the best course of action in terms of treatment. In this case, attempts may be made to record an EEG while
2166-421: A maternal copy of UBE3A and a paternal copy of UBE3A . In certain areas of the developing brain, the paternal copy of UBE3A is inactivated through a process known as imprinting and the fetus relies on the functioning maternal copy of UBE3A in order to develop normally. In an individual with AS, however, the maternal UBE3A gene is absent or not functioning normally. This can be due to genetic errors such as
2280-592: A parent with the disorder ( autosomal dominant inheritance). When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease . Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA (due to their size). There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. More than 600 genetic disorders are treatable. Around 1 in 50 people are affected by
2394-421: A person is in a state of relaxed wakefulness and are mostly prominent over the parietal and occipital sites. During intense mental activity , beta waves are more prominent in frontal areas as well as other regions. If a relaxed person is told to open their eyes, one observes alpha activity decreasing and an increase in beta activity. Theta and delta waves are not generally seen in wakefulness - if they are, it
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#17327805617202508-787: A person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. The chance a child will inherit the mutated gene is 50%. Autosomal dominant conditions sometimes have reduced penetrance , which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease. Examples of this type of disorder are Huntington's disease , neurofibromatosis type 1 , neurofibromatosis type 2 , Marfan syndrome , hereditary nonpolyposis colorectal cancer , hereditary multiple exostoses (a highly penetrant autosomal dominant disorder), tuberous sclerosis , Von Willebrand disease , and acute intermittent porphyria . Birth defects are also called congenital anomalies. Two copies of
2622-744: A quantitative biomarkers to "chart progression of AS and as clinical outcome measures". Slow delta activity (~3 Hz) is greatly increased in AS relative to typically developing children, yet more pronounced in children with partial 15q deletions as opposed to those with etiologies principally affecting UBE3A . Theta activity (~5 Hz) is much greater in children with partial 15q deletions. Thus, delta activity appears to be chiefly reflective of UBE3A dysfunction with some modulation from other 15q genes, whereas theta activity may be an electrophysiological readout of genes beyond UBE3A such as GABRA5 , GABRB3 , and GABRG3 . The diagnosis of Angelman syndrome
2736-506: A research method). In cases where significant brain injury is suspected, e.g., after cardiac arrest, EEG can provide some prognostic information. If a patient with epilepsy is being considered for resective surgery to treat epilepsy, it is often necessary to localize the focus (source) of the epileptic brain activity with a resolution greater than what is provided by scalp EEG. In these cases, neurosurgeons typically implant strips and grids of electrodes or penetrating depth electrodes under
2850-410: A smaller parcel of brain surface) allow for better spatial resolution to narrow down the areas critical for seizure onset and propagation. Some clinical sites record data from penetrating microelectrodes. Sometimes it is more convenient or clinically necessary to perform ambulatory EEG recordings in the home of the person being tested. These studies typically have a duration of 24–72 hours. EEG and
2964-428: A span of hours. Therefore, research has been directed to developing dry and semi-dry EEG bioelectronic interfaces. Dry electrode signals depend upon mechanical contact. Therefore, it can be difficult getting a usable signal because of impedance between the skin and the electrode. Some EEG systems attempt to circumvent this issue by applying a saline solution. Others have a semi dry nature and release small amounts of
3078-465: Is Leber's hereditary optic neuropathy . It is important to stress that the vast majority of mitochondrial diseases (particularly when symptoms develop in early life) are actually caused by a nuclear gene defect, as the mitochondria are mostly developed by non-mitochondrial DNA. These diseases most often follow autosomal recessive inheritance. Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with
3192-447: Is a reliable indication of the occurrence of neural output. Not only do EEGs capture dendritic currents almost exclusively as opposed to axonal currents, they also show a preference for activity on populations of parallel dendrites and transmitting current in the same direction at the same time. Pyramidal neurons of cortical layers II/III and V extend apical dendrites to layer I. Currents moving up or down these processes underlie most of
3306-550: Is a sign of brain dysfunction. EEG can detect abnormal electrical discharges such as sharp waves , spikes, or spike-and-wave complexes, as observable in people with epilepsy ; thus, it is often used to inform medical diagnosis . EEG can detect the onset and spatio-temporal (location and time) evolution of seizures and the presence of status epilepticus . It is also used to help diagnose sleep disorders , depth of anesthesia , coma , encephalopathies , cerebral hypoxia after cardiac arrest , and brain death . EEG used to be
3420-410: Is a very large amplitude 2–3 Hz rhythm most prominent in prefrontal leads. Next most common is a symmetrical 4–6 Hz high voltage rhythm. The third pattern, 3–6 Hz activity punctuated by spikes and sharp waves in occipital leads, is associated with eye closure. Paroxysms of laughter have no relation to the EEG, ruling out this feature as a gelastic phenomenon. EEG anomalies may be used as
3534-413: Is about 10 μV to 100 μV in amplitude when measured from the scalp. Since an EEG voltage signal represents a difference between the voltages at two electrodes, the display of the EEG for the reading encephalographer may be set up in one of several ways. The representation of the EEG channels is referred to as a montage. When analog (paper) EEGs are used, the technologist switches between montages during
Angelman syndrome - Misplaced Pages Continue
3648-405: Is also a strong environmental component to many of them (e.g., blood pressure ). Other such cases include: A chromosomal disorder is a missing, extra, or irregular portion of chromosomal DNA. It can be from an atypical number of chromosomes or a structural abnormality in one or more chromosomes. An example of these disorders is Trisomy 21 (the most common form of Down syndrome ), in which there
3762-423: Is also considered a recessive condition, but heterozygous carriers have increased resistance to malaria in early childhood, which could be described as a related dominant condition. When a couple where one partner or both are affected or carriers of a single-gene disorder wish to have a child, they can do so through in vitro fertilization, which enables preimplantation genetic diagnosis to occur to check whether
3876-412: Is an extra copy of chromosome 21 in all cells. Due to the wide range of genetic disorders that are known, diagnosis is widely varied and dependent of the disorder. Most genetic disorders are diagnosed pre-birth , at birth , or during early childhood however some, such as Huntington's disease , can escape detection until the patient begins exhibiting symptoms well into adulthood. The basic aspects of
3990-525: Is an integrated system made of an array of capacitive sensors with local integrated circuitry housed in a package with batteries to power the circuitry. This level of integration was required to achieve the functional performance obtained by the electrode. The electrode was tested on an electrical test bench and on human subjects in four modalities of EEG activity, namely: (1) spontaneous EEG, (2) sensory event-related potentials, (3) brain stem potentials, and (4) cognitive event-related potentials. The performance of
4104-463: Is attached to an individual wire. Some systems use caps or nets into which electrodes are embedded; this is particularly common when high-density arrays of electrodes are needed. Electrode locations and names are specified by the International 10–20 system for most clinical and research applications (except when high-density arrays are used). This system ensures that the naming of electrodes
4218-484: Is based on: Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (US); these criteria underwent revision in 2005. Seizures are a consequence, as is excessive laughter, which is a major hindrance to early diagnosis. Other conditions that can appear similar include: There is currently no approved cure available. The epilepsy can be controlled by
4332-412: Is caused by the lack of expression of a gene known as UBE3A during development. This gene is located within a region of chromosome 15 known as 15q11-q13 and is part of the ubiquitin pathway. In fact, UBE3A codes for a very selective E6-AP ubiquitin ligase for which MAPK1 , PRMT5 , CDK1 , CDK4 , β-catenin , and UBXD8 have been identified as ubiquitination targets Typically, a fetus inherits
4446-413: Is confirmatory of epilepsy in nearly all cases (high specificity ), however up to 3.5% of the general population may have epileptiform abnormalities in an EEG without ever having had a seizure (low false positive rate ) or with a very low risk of developing epilepsy in the future. When a routine EEG is normal and there is a high suspicion or need to confirm epilepsy, it may be repeated or performed with
4560-506: Is consistent across laboratories. In most clinical applications, 19 recording electrodes (plus ground and system reference) are used. A smaller number of electrodes are typically used when recording EEG from neonates . Additional electrodes can be added to the standard set-up when a clinical or research application demands increased spatial resolution for a particular area of the brain. High-density arrays (typically via cap or net) can contain up to 256 electrodes more-or-less evenly spaced around
4674-427: Is delayed or processed differently in AS. This may be caused by the altered cortical morphology seen in AS in the precuneus , a region of the brain involved in self-reflection and memory. Similarly, both adults and children with AS show a delay in processing speed in speech processing, and this should be accounted for during communication. An experimental treatment, currently in clinical development by Roche , targets
Angelman syndrome - Misplaced Pages Continue
4788-514: Is due to a lack of function of part of chromosome 15 , typically due to a new mutation rather than one inherited . Most often it is due to a deletion or mutation of the UBE3A gene on that chromosome. Occasionally it is due to the inheritance of two copies of chromosome 15 from the father and none from the mother ( paternal uniparental disomy ). As the father's versions are inactivated by a process known as genomic imprinting , no functional version of
4902-478: Is limited by AS, but many people with the disorder are able to learn non-verbal communication skills to express their needs. Deictic gesturing (i.e, pointing to an object) is the most commonly used form of non-symbolic communication in AS, followed by physically manipulating others (such as moving a caregiver's hand to a specific object or guiding a person to a new location) and non-speech vocalizations. Some are able to use symbolic communication such as signing, though
5016-410: Is maintained by billions of neurons . Neurons are electrically charged (or "polarized") by membrane transport proteins that pump ions across their membranes. Neurons are constantly exchanging ions with the extracellular milieu, for example to maintain resting potential and to propagate action potentials . Ions of similar charge repel each other, and when many ions are pushed out of many neurons at
5130-445: Is most often performed by visual inspection of the tracing or quantitative EEG analysis . Voltage fluctuations measured by the EEG bioamplifier and electrodes allow the evaluation of normal brain activity . As the electrical activity monitored by EEG originates in neurons in the underlying brain tissue , the recordings made by the electrodes on the surface of the scalp vary in accordance with their orientation and distance to
5244-402: Is named after British pediatrician Harry Angelman , who first described the syndrome in 1965. An older term, happy puppet syndrome , is generally considered pejorative . Prader–Willi syndrome is a separate condition, caused by a similar loss of the father's chromosome 15. Signs and symptoms of Angelman syndrome and their relative frequency in affected individuals are: Angelman syndrome
5358-488: Is not possible with CT, PET, or MRI. Derivatives of the EEG technique include evoked potentials (EP), which involves averaging the EEG activity time-locked to the presentation of a stimulus of some sort (visual, somatosensory , or auditory). Event-related potentials ( ERPs ) refer to averaged EEG responses that are time-locked to more complex processing of stimuli; this technique is used in cognitive science , cognitive psychology , and psychophysiological research. EEG
5472-421: Is only possible through the circumvention of infertility by medical intervention. This type of inheritance, also known as maternal inheritance, is the rarest and applies to the 13 genes encoded by mitochondrial DNA . Because only egg cells contribute mitochondria to the developing embryo, only mothers (who are affected) can pass on mitochondrial DNA conditions to their children. An example of this type of disorder
5586-416: Is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity , penetrance , and expressivity. On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. This does not mean that the genes cannot eventually be located and studied. There
5700-425: Is performed for Angelman syndrome looks for methylation on the gene's neighbor SNRPN , which is silenced by methylation on the maternal copy of the gene. The electroencephalogram (EEG) in AS is usually abnormal, more so than clinically expected. This EEG facilitates the differential diagnosis of AS, but is not pathognomonic . Three distinct interictal patterns are seen in these patients. The most common pattern
5814-452: Is processed in the same manner as digital scalp EEG (above), with a couple of caveats. ECoG is typically recorded at higher sampling rates than scalp EEG because of the requirements of Nyquist theorem – the subdural signal is composed of a higher predominance of higher frequency components. Also, many of the artifacts that affect scalp EEG do not impact ECoG, and therefore display filtering is often not needed. A typical adult human EEG signal
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#17327805617205928-423: Is stored electronically and can be filtered for display. Typical settings for the high-pass filter and a low-pass filter are 0.5–1 Hz and 35–70 Hz respectively. The high-pass filter typically filters out slow artifact, such as electrogalvanic signals and movement artifact, whereas the low-pass filter filters out high-frequency artifacts, such as electromyographic signals. An additional notch filter
6042-465: Is the gold standard diagnostic procedure to confirm epilepsy . The sensitivity of a routine EEG to detect interictal epileptiform discharges at epilepsy centers has been reported to be in the range of 29–55%. Given the low to moderate sensitivity, a routine EEG (typically with a duration of 20–30 minutes) can be normal in people that have epilepsy. When an EEG shows interictal epileptiform discharges (e.g. sharp waves, spikes, spike-and-wave , etc.) it
6156-469: Is then filtered (next paragraph), and the EEG signal is output as the deflection of pens as paper passes underneath. Most EEG systems these days, however, are digital, and the amplified signal is digitized via an analog-to-digital converter , after being passed through an anti-aliasing filter . Analog-to-digital sampling typically occurs at 256–512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz are used in some research applications. During
6270-600: Is typically used to remove artifact caused by electrical power lines (60 Hz in the United States and 50 Hz in many other countries). The EEG signals can be captured with opensource hardware such as OpenBCI and the signal can be processed by freely available EEG software such as EEGLAB or the Neurophysiological Biomarker Toolbox . As part of an evaluation for epilepsy surgery, it may be necessary to insert electrodes near
6384-548: The GABAA α5 receptor . Alogabat is a small molecule that acts as a positive allosteric modulator ( PAMs ) of the receptor. It does not involve replacing or activating the UBE3A gene, instead it is a mechanism aimed at improving various symptoms of AS such as learning, sleep, and seizure control. The severity of the symptoms associated with Angelman syndrome varies significantly across the population of those affected. Some speech and
6498-548: The dura mater , through either a craniotomy or a burr hole . The recording of these signals is referred to as electrocorticography (ECoG), subdural EEG (sdEEG), intracranial EEG (icEEG), or stereotactic EEG (sEEG). The signal recorded from ECoG is on a different scale of activity than the brain activity recorded from scalp EEG. Low-voltage, high-frequency components that cannot be seen easily (or at all) in scalp EEG can be seen clearly in ECoG. Further, smaller electrodes (which cover
6612-600: The electrodes will not contribute directly to an EEG; these include the base of the cortical gyrus , mesial walls of the major lobes , hippocampus , thalamus , and brain stem . A healthy human EEG will show certain patterns of activity that correlate with how awake a person is. The range of frequencies one observes are between 1 and 30 Hz, and amplitudes will vary between 20 and 100 μV. The observed frequencies are subdivided into various groups: alpha (8–13 Hz), beta (13–30 Hz), delta (0.5–4 Hz), and theta (4–7 Hz). Alpha waves are observed when
6726-413: The postsynaptic potentials of pyramidal neurons in the neocortex and allocortex . It is typically non-invasive, with the EEG electrodes placed along the scalp (commonly called "scalp EEG") using the International 10–20 system , or variations of it. Electrocorticography , involving surgical placement of electrodes, is sometimes called "intracranial EEG" . Clinical interpretation of EEG recordings
6840-405: The 2011 Philippine drama series Budoy , the titular character and main protagonist Budoy Maniego (played by Filipino actor Gerald Anderson ) is diagnosed with Angelman syndrome. Genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome . It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by
6954-594: The Danish study showed a minimum AS prevalence of about 1/10,000. Harry Angelman , a pediatrician working in Warrington , England, first reported three children with this condition in 1965. Angelman later described his choice of the title "Puppet Children" to describe these cases as being related to an oil painting he had seen while vacationing in Italy: The history of medicine is full of interesting stories about
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#17327805617207068-679: The EEG abnormalities are less obvious. Medication is typically advisable to those with seizure disorders. Often overlooked is the contribution of the poor sleep patterns to the frequency and/or severity of the seizures. Medication may be worthwhile to help deal with this issue and improve the prognosis with respect to seizures and sleep. Also noteworthy are the reports that the frequency and severity of seizures temporarily escalate in pubescent Angelman syndrome girls, but do not seem to affect long-term health.The facial features remain recognizable with age, but many adults with AS look remarkably youthful for their age. Puberty and menstruation begin at around
7182-399: The X chromosome. Males are much more frequently affected than females, because they only have the one X chromosome necessary for the condition to present. The chance of passing on the disorder differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected (since they receive their father's Y chromosome), but his daughters will be carriers of one copy of
7296-443: The Y chromosome. These conditions may only be transmitted from the heterogametic sex (e.g. male humans) to offspring of the same sex. More simply, this means that Y-linked disorders in humans can only be passed from men to their sons; females can never be affected because they do not possess Y-allosomes. Y-linked disorders are exceedingly rare but the most well-known examples typically cause infertility. Reproduction in such conditions
7410-448: The active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy . This includes physical therapy and pain management . The treatment of genetic disorders is an ongoing battle, with over 1,800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating
7524-522: The average age. Sexual development is thought to be unaffected, as evidenced by a single reported case of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome. The majority of those with AS achieve continence by day and some by night. Angelman syndrome is not a degenerative syndrome, and thus people with AS may improve their living skills with support. Dressing skills are variable and usually limited to items of clothing without buttons or zippers. Most adults can eat with
7638-582: The brain after concussion, however, at this time there are no advanced imaging techniques that can be used clinically to diagnose or monitor recovery from concussion. Several other methods to study brain function exist, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), magnetoencephalography (MEG), nuclear magnetic resonance spectroscopy (NMR or MRS), electrocorticography (ECoG), single-photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and event-related optical signal (EROS). Despite
7752-440: The brain, a functioning maternal copy of UBE3A is essential for proper development. Region 15q11-13 is implicated in both Angelman syndrome and Prader–Willi syndrome (PWS). While AS results from mutation, loss or abnormal imprinting involving the UBE3A gene within this region on the maternal chromosome, loss of a different cluster of genes within the same region on the paternal chromosome causes PWS. The methylation test that
7866-418: The care of patients with seizures. Outpatient ambulatory video EEGs typically last one to three days. An admission to an Epilepsy Monitoring Unit typically lasts several days but may last for a week or longer. While in the hospital, seizure medications are usually withdrawn to increase the odds that a seizure will occur during admission. For reasons of safety, medications are not withdrawn during an EEG outside of
7980-501: The cortex are thought to produce the most EEG signal because they are well-aligned and fire together. Because voltage field gradients fall off with the square of distance, activity from deep sources is more difficult to detect than currents near the skull. Scalp EEG activity shows oscillations at a variety of frequencies. Several of these oscillations have characteristic frequency ranges , spatial distributions and are associated with different states of brain functioning (e.g., waking and
8094-416: The cortex, inside sulci , in midline or deep structures (such as the cingulate gyrus or hippocampus ), or producing currents that are tangential to the skull, make far less contribution to the EEG signal. EEG recordings do not directly capture axonal action potentials . An action potential can be accurately represented as a current quadrupole , meaning that the resulting field decreases more rapidly than
8208-490: The deletion or mutation of a segment of chromosome 15, uniparental disomy , or translocation . While Angelman syndrome can be caused by a single mutation in the UBE3A gene, the most common genetic defect leading to Angelman syndrome is a 5- to 7-Mb (megabase) maternal deletion in chromosomal region 15q11.2-q13. Specifically, the paternal copy of UBE3A is known to be imprinted within the hippocampus, cortex, thalamus, olfactory bulb, and cerebellum. Therefore, in these areas of
8322-455: The discovery of illnesses. The saga of Angelman's syndrome is one such story. It was purely by chance that nearly thirty years ago (e.g. [ sic ], circa 1964) three handicapped children were admitted at various times to my children's ward in England. They had a variety of disabilities and although at first sight they seemed to be suffering from different conditions I felt that there
8436-440: The divisions between autosomal and X-linked types are (since the latter types are distinguished purely based on the chromosomal location of the gene). For example, the common form of dwarfism , achondroplasia , is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe and usually lethal skeletal disorder, one that achondroplasics could be considered carriers for. Sickle cell anemia
8550-526: The dry electrode compared favorably with that of the standard wet electrodes in terms of skin preparation, no gel requirements (dry), and higher signal-to-noise ratio. In 1999 researchers at Case Western Reserve University , in Cleveland , Ohio , led by Hunter Peckham, used 64-electrode EEG skullcap to return limited hand movements to quadriplegic Jim Jatich. As Jatich concentrated on simple but opposite concepts like up and down, his beta-rhythm EEG output
8664-660: The early eighties. Case reports from the United States first began appearing in the medical literature in the early 1980s. In 1987, it was first noted that around half of the children with AS have a small piece of chromosome 15 missing ( chromosome 15q partial deletion ). Many poems in Richard Price 's poetry collections Hand Held (1997), Lucky Day (2005), and Small World (2012) reflect on his daughter, who has Angelman syndrome. In October 2007, actor Colin Farrell publicly announced that his son has Angelman syndrome. In
8778-421: The effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes . Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person's risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because
8892-426: The embryo has the genetic disorder. Most congenital metabolic disorders known as inborn errors of metabolism result from single-gene defects. Many such single-gene defects can decrease the fitness of affected people and are therefore present in the population in lower frequencies compared to what would be expected based on simple probabilistic calculations. Only one mutated copy of the gene will be necessary for
9006-608: The first single and also multichannel dry active electrode arrays using micro-machining. The single channel dry EEG electrode construction and results were published in 1994. The arrayed electrode was also demonstrated to perform well compared to silver / silver chloride electrodes. The device consisted of four sites of sensors with integrated electronics to reduce noise by impedance matching . The advantages of such electrodes are: (1) no electrolyte used, (2) no skin preparation, (3) significantly reduced sensor size, and (4) compatibility with EEG monitoring systems. The active electrode array
9120-454: The following disorders: It can also: EEG can also be used in intensive care units for brain function monitoring to monitor for non-convulsive seizures/non-convulsive status epilepticus, to monitor the effect of sedative/anesthesia in patients in medically induced coma (for treatment of refractory seizures or increased intracranial pressure ), and to monitor for secondary brain damage in conditions such as subarachnoid hemorrhage (currently
9234-817: The foundational skills such as finger isolation, motor planning, hand-eye coordination, spatial awareness, and refining gestures. This is important because individuals with Angelman Syndrome who already possess some form of non-verbal communication have a much harder time adapting to changes in a new or existing AAC device because they can communicate their needs much faster nonverbally. Occupational therapists can assist individuals with Angelman syndrome with many other skills as well. Many individuals with Angelman syndrome also have difficulty processing sensory information and responding appropriately to sensory stimuli. Occupational therapists can work together with these individuals to improve their visual perceptual skills and increase their sensory awareness. Expressive verbal communication
9348-414: The gel upon contact with the scalp. Another solution uses spring loaded pin setups. These may be uncomfortable. They may also be dangerous if they were used in a situation where a patient could bump their head since they could become lodged after an impact trauma incident. Currently, headsets are available incorporating dry electrodes with up to 30 channels. Such designs are able to compensate for some of
9462-408: The gene must be mutated for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene and are referred to as genetic carriers . Each parent with a defective gene normally do not have symptoms. Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having
9576-421: The gene remains. Diagnosis is based on symptoms and possibly genetic testing . No cure is available. Treatment is generally supportive in nature. Anti-seizure medications are used in those with seizures. Physical therapy and bracing may help with walking. Those affected have a nearly normal life expectancy . AS affects 1 in 12,000 to 20,000 people. Males and females are affected with equal frequency. It
9690-464: The general population. Though the prevalence of Angelman syndrome is not precisely known, there are some estimates. The best data available are from studies of school age children, ages 6–13 years, living in Sweden and from Denmark where the diagnosis of AS children in medical clinics was compared to an 8-year period of about 45,000 births. The Swedish study showed an AS prevalence of about 1/20,000 and
9804-675: The hospital. Ambulatory video EEGs, therefore, have the advantage of convenience and are less expensive than a hospital admission, but they also have the disadvantage of a decreased probability of recording a clinical event. Epilepsy monitoring is often considered when patients continue having events despite being on anti-seizure medications or if there is concern that the patient's events have an alternate diagnosis, e.g., psychogenic non-epileptic seizures , syncope (fainting) , sub-cortical movement disorders , migraine variants, stroke, etc. In cases of epileptic seizures, continuous EEG monitoring helps to characterize seizures and localize/lateralize
9918-409: The interpretation of EEGs for clinical purposes. This is done by visual inspection of the waveforms, called graphoelements. The use of computer signal processing of the EEG – so-called quantitative electroencephalography – is somewhat controversial when used for clinical purposes (although there are many research uses). In the early 1990s Babak Taheri, at University of California, Davis demonstrated
10032-643: The mutated gene. A woman who is a carrier of an X-linked recessive disorder (X X ) has a 50% chance of having sons who are affected and a 50% chance of having daughters who are carriers of one copy of the mutated gene. X-linked recessive conditions include the serious diseases hemophilia A , Duchenne muscular dystrophy , and Lesch–Nyhan syndrome , as well as common and less serious conditions such as male pattern baldness and red–green color blindness . X-linked recessive conditions can sometimes manifest in females due to skewed X-inactivation or monosomy X ( Turner syndrome ). Y-linked disorders are caused by mutations on
10146-473: The ones produced by the current dipole of post-synaptic potentials. In addition, since EEGs represent averages of thousands of neurons, a large population of cells in synchronous activity is necessary to cause a significant deflection on the recordings. Action potentials are very fast and, as a consequence, the chances of field summation are slim. However, neural backpropagation , as a typically longer dendritic current dipole, can be picked up by EEG electrodes and
10260-1003: The past, carrying one of the faulty genes led to a slight protection against an infectious disease or toxin such as tuberculosis or malaria . Such disorders include cystic fibrosis, sickle cell disease, phenylketonuria and thalassaemia . X-linked dominant disorders are caused by mutations in genes on the X chromosome . Only a few disorders have this inheritance pattern, with a prime example being X-linked hypophosphatemic rickets . Males and females are both affected in these disorders, with males typically being more severely affected than females. Some X-linked dominant conditions, such as Rett syndrome , incontinentia pigmenti type 2, and Aicardi syndrome , are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. Exceptions to this finding are extremely rare cases in which boys with Klinefelter syndrome (44+xxy) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of
10374-606: The presence of characteristic abnormalities in fetal development through ultrasound , or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis . Not all genetic disorders directly result in death; however, there are no known cures for genetic disorders. Many genetic disorders affect stages of development, such as Down syndrome , while others result in purely physical symptoms such as muscular dystrophy . Other disorders, such as Huntington's disease , show no signs until adulthood. During
10488-454: The prevalence of this ability is related to both genetic etiology and epilepsy status, with non-deletion etiologies without epilepsy showing the highest prevalence of symbolic communication skills. People with AS tend to have much higher receptive language abilities than expressive; recent studies have shown that patients with AS have typical auditory brain region responses to speech but atypical memory responses, suggesting that word meaning recall
10602-542: The recording in order to highlight or better characterize certain features of the EEG. With digital EEG, all signals are typically digitized and stored in a particular (usually referential) montage; since any montage can be constructed mathematically from any other, the EEG can be viewed by the electroencephalographer in any display montage that is desired. The EEG is read by a clinical neurophysiologist or neurologist (depending on local custom and law regarding medical specialities ), optimally one who has specific training in
10716-422: The recording, a series of activation procedures may be used. These procedures may induce normal or abnormal EEG activity that might not otherwise be seen. These procedures include hyperventilation, photic stimulation (with a strobe light), eye closure, mental activity, sleep and sleep deprivation. During (inpatient) epilepsy monitoring, a patient's typical seizure medications may be withdrawn. The digital EEG signal
10830-677: The region of the brain from which a seizure originates. This can help identify appropriate non-medication treatment options. In clinical use, EEG traces are visually analyzed by neurologists to look at various features. Increasingly, quantitative analysis of EEG is being used in conjunction with visual analysis. Quantitative analysis displays like power spectrum analysis, alpha-delta ratio, amplitude integrated EEG, and spike detection can help quickly identify segments of EEG that need close visual analysis or, in some cases, be used as surrogates for quick identification of seizures in long-term recordings. An EEG might also be helpful for diagnosing or treating
10944-434: The related study of ERPs are used extensively in neuroscience , cognitive science , cognitive psychology , neurolinguistics , and psychophysiological research, as well as to study human functions such as swallowing. Any EEG techniques used in research are not sufficiently standardised for clinical use, and many ERP studies fail to report all of the necessary processing steps for data collection and reduction, limiting
11058-500: The relatively poor spatial sensitivity of EEG, the "one-dimensional signals from localised peripheral regions on the head make it attractive for its simplistic fidelity and has allowed high clinical and basic research throughput". Thus, EEG possesses some advantages over some of those other techniques: EEG also has some characteristics that compare favorably with behavioral testing: Simultaneous EEG recordings and fMRI scans have been obtained successfully, though recording both at
11172-607: The reproducibility and replicability of many studies. Based on a 2024 systematic literature review and meta analysis commissioned by the Patient-Centered Outcomes Research Institute (PCORI), EEG scans cannot be used reliably to assist in making a clinical diagnosis of ADHD. However, EEG continues to be used in research on mental disabilities, such as auditory processing disorder (APD), ADD , and ADHD . EEGs have also been studied for their utility in detecting neurophysiological changes in
11286-911: The same time effectively requires that several technical difficulties be overcome, such as the presence of ballistocardiographic artifact, MRI pulse artifact and the induction of electrical currents in EEG wires that move within the strong magnetic fields of the MRI. While challenging, these have been successfully overcome in a number of studies. MRI's produce detailed images created by generating strong magnetic fields that may induce potentially harmful displacement force and torque. These fields produce potentially harmful radio frequency heating and create image artifacts rendering images useless. Due to these potential risks, only certain medical devices can be used in an MR environment. Similarly, simultaneous recordings with MEG and EEG have also been conducted, which has several advantages over using either technique alone: Recently,
11400-408: The same time, they can push their neighbours, who push their neighbours, and so on, in a wave. This process is known as volume conduction. When the wave of ions reaches the electrodes on the scalp, they can push or pull electrons on the metal in the electrodes. Since metal conducts the push and pull of electrons easily, the difference in push or pull voltages between any two electrodes can be measured by
11514-401: The scalp. Each electrode is connected to one input of a differential amplifier (one amplifier per pair of electrodes); a common system reference electrode is connected to the other input of each differential amplifier. These amplifiers amplify the voltage between the active electrode and the reference (typically 1,000–100,000 times, or 60–100 dB of power gain). In analog EEG, the signal
11628-437: The signal quality degradation related to high impedances by optimizing pre-amplification, shielding and supporting mechanics. EEG has several limitations. Most important is its poor spatial resolution. EEG is most sensitive to a particular set of post-synaptic potentials: those generated in superficial layers of the cortex, on the crests of gyri directly abutting the skull and radial to the skull. Dendrites which are deeper in
11742-423: The significantly large number of genetic disorders, approximately 1 in 21 people are affected by a genetic disorder classified as " rare " (usually defined as affecting less than 1 in 2,000 people). Most genetic disorders are rare in themselves. There are well over 6,000 known genetic disorders, and new genetic disorders are constantly being described in medical literature. The earliest known genetic condition in
11856-425: The source of the activity. Furthermore, the value recorded is distorted by intermediary tissues and bones, which act in a manner akin to resistors and capacitors in an electrical circuit . This means that not all neurons will contribute equally to an EEG signal, with an EEG predominately reflecting the activity of cortical neurons near the electrodes on the scalp. Deep structures within the brain further away from
11970-401: The specific factors that cause most of these disorders have not yet been identified. Studies that aim to identify the cause of complex disorders can use several methodological approaches to determine genotype – phenotype associations. One method, the genotype-first approach , starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This
12084-525: The specific genetic mechanism underlying the condition is thought to correlate to the general prognosis of the affected person. On one end of the spectrum, a mutation to the UBE3A gene is thought to correlate to the least affected, whereas larger deletions on chromosome 15 are thought to correspond to the most affected. The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The seizures decrease in frequency and often cease altogether and
12198-458: The surface of the brain, under the surface of the dura mater . This is accomplished via burr hole or craniotomy . This is referred to variously as "electrocorticography (ECoG)" , "intracranial EEG (I-EEG)" or "subdural EEG (SD-EEG)". Depth electrodes may also be placed into brain structures, such as the amygdala or hippocampus , structures, which are common epileptic foci and may not be "seen" clearly by scalp EEG. The electrocorticographic signal
12312-442: The symptoms of the disorders in an attempt to improve patient quality of life . Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of the disease. A major obstacle has been the delivery of genes to the appropriate cell, tissue, and organ affected by the disorder. Researchers have investigated how they can introduce
12426-433: The two is complex, with a combination of EEG power in the gamma band and phase in the delta band relating most strongly to neuron spike activity. In conventional scalp EEG, the recording is obtained by placing electrodes on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Many systems typically use electrodes, each of which
12540-447: The use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because people with AS often have multiple types of seizures. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Mild laxatives are also used frequently to encourage regular bowel movements. Additionally, among
12654-420: The various sleep stages ). These oscillations represent synchronized activity over a network of neurons. The neuronal networks underlying some of these oscillations are understood (e.g., the thalamocortical resonance underlying sleep spindles ), while many others are not (e.g., the system that generates the posterior basic rhythm). Research that measures both EEG and neuron spiking finds the relationship between
12768-614: Was a common cause for their illness. The diagnosis was purely a clinical one because in spite of technical investigations which today are more refined I was unable to establish scientific proof that the three children all had the same handicap. In view of this I hesitated to write about them in the medical journals. However, when on holiday in Italy I happened to see an oil painting in the Castelvecchio Museum in Verona called ...
12882-470: Was analysed using software to identify patterns in the noise. A basic pattern was identified and used to control a switch: Above average activity was set to on, below average off. As well as enabling Jatich to control a computer cursor the signals were also used to drive the nerve controllers embedded in his hands, restoring some movement. In 2018, a functional dry electrode composed of a polydimethylsiloxane elastomer filled with conductive carbon nanofibers
12996-522: Was reported. This research was conducted at the U.S. Army Research Laboratory . EEG technology often involves applying a gel to the scalp which facilitates strong signal-to-noise ratio. This results in more reproducible and reliable experimental results. Since patients dislike having their hair filled with gel, and the lengthy setup requires trained staff on hand, utilizing EEG outside the laboratory setting can be difficult. Additionally, it has been observed that wet electrode sensors' performance reduces after
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