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What causes Holt-Oram syndrome? Holt-Oram syndrome is caused by changes (mutations) in the TBX5 gene. This gene gives the body instructions for making a protein involved in the development of the heart and upper limbs before birth. In particular, this gene seems important for dividing the developing heart into four cha...
Standard treatments for breast cancer include - surgery that takes out the cancer and some surrounding tissue - radiation therapy that uses high-energy beams to kill cancer cells and shrink tumors and some surrounding tissue. - chemotherapy that uses anti-cancer drugs to kill cancer most cells - hormone therapy that...
How might Klippel-Feil syndrome be treated? There is no cure for Klippel Feil syndrome (KFS); treatment is generally symptomatic and supportive. Management depends on the features and severity in each person, and can be life-long. Careful evaluation, consistent follow-up, and coordination with various specialists are n...
How is congenital contractural arachnodactyly inherited? This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from an affected parent. Other cases result from new m...
Summary : Clinical trials are research studies that test how well new medical approaches work in people. Each study answers scientific questions and tries to find better ways to prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a treatment that is already available. ...
Mutations in the FTCD gene cause glutamate formiminotransferase deficiency. The FTCD gene provides instructions for making the enzyme formiminotransferase cyclodeaminase. This enzyme is involved in the last two steps in the breakdown (metabolism) of the amino acid histidine, a building block of most proteins. It also p...
Peutz-Jeghers syndrome (PJS) is an inherited condition that is associated with an increased risk of growths along the lining of the gastrointestinal tract (called hamartomatous polyps) and certain types of cancer. Most affected people also have characteristic dark blue to dark brown macules around the mouth, eyes, and ...
Mutations in the TTR gene cause transthyretin amyloidosis. The TTR gene provides instructions for producing a protein called transthyretin. Transthyretin transports vitamin A (retinol) and a hormone called thyroxine throughout the body. To transport retinol and thyroxine, four transthyretin proteins must be attached (b...
These resources address the diagnosis or management of Marinesco-Sjgren syndrome: - Gene Review: Gene Review: Marinesco-Sjogren Syndrome - Genetic Testing Registry: Marinesco-Sjgren syndrome - MedlinePlus Encyclopedia: Congenital Cataract - MedlinePlus Encyclopedia: Hypogonadism - MedlinePlus Encyclopedia: Muscle ...
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
McCune-Albright syndrome is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein. In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimatel...
Trichohepatoenteric syndrome can be caused by mutations in the TTC37 or SKIV2L gene. These genes provide instructions for making proteins whose functions have not been confirmed. Researchers speculate that they work together with other proteins within cells to help recognize and break down excess or abnormal messenger ...
Mutations in the FGFR3 gene cause thanatophoric dysplasia. Both types of this condition result from mutations in the FGFR3 gene. This gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Mutations in this gene cause the FGFR3 protein to be overly ...
How is 17q23.1q23.2 microdeletion syndrome diagnosed? The deletion can be identified by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH).
Alpha thalassemia X-linked intellectual disability syndrome results from mutations in the ATRX gene. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (e...
How might multifocal motor neuropathy be treated? Multifocal motor neuropathy (MMN) is considered treatable with intravenous immune globulin (IVIG). Early treatment shortly after symptoms begin is recommended. Most people have a fairly rapid improvement in weakness with IVIG, but the improvement generally does not last...
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Chromoblastomycosis is a chronic fungal infection characterized by raised and crusted lesions which affect the skin and subcutaneous tissue. It most often occurs on the limbs, but can affect any area of the body. Chromoblastomycosis is caused by several fungi found in soil, wood, and decaying plant material. It usually...
Is genetic testing available for Gilbert syndrome? The Genetic Testing Registry provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care pr...
The number of new cases of oral cavity and oropharyngeal cancer and the number of deaths from oral cavity and oropharyngeal cancer varies by race and gender. Over the past ten years, the number of new cases and deaths from oral cavity and oropharyngeal cancer slightly increased in white men and women. The number slight...
How is Klippel Feil syndrome diagnosed? Klippel Feil syndrome (KFS) is typically diagnosed when X-rays or other imaging techniques show fusion of cervical vertebrae. X-rays of the entire spine should be performed to detect other spinal abnormalities, and additional imaging studies may be needed to assess the extent of ...
2q37 deletion syndrome is a rare chromosome condition that can affect many parts of the body. Approximately 100 cases have been reported worldwide. This condition is characterized by weak muscle tone (hypotonia) in infancy, mild to severe intellectual disability and developmental delay, behavioral problems, characteris...
Anxiety disorders are a collection of disorders that include generalized anxiety disorder (GAD), social phobia, and panic disorder.
Obsessive-compulsive disorder (OCD) is a type of anxiety disorder. If you have OCD, you have frequent, upsetting thoughts called obsessions. To try to control the thoughts, you feel an overwhelming urge to repeat certain rituals or behaviors. These are called compulsions. Examples of obsessions are a fear of germs o...
The familial form of thrombotic thrombocytopenic purpura is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and s...
Being exposed to certain types of radiation may increase the risk of salivary cancer. Anything that increases the chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesnt mean that you will not get cancer. Talk with your doctor if y...
Cowden syndrome and Cowden-like syndrome are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the condition and increase the risk of developing cancer. In some cases, an affected person inherits the mutation from one affected parent. Other cases ma...
Is 22q11.2 deletion syndrome inherited? Most cases of 22q11.2 deletion syndrome are not inherited from a parent and are caused by a random error during the formation of egg or sperm cells, or during early fetal development. In about 10% of cases, the deletion is inherited from a parent with the deletion. All people wit...
Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all children in the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often in the winter and spring. It is very easy for children with the virus ...
The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct research related to iniencephaly in laboratories at the NIH and also support additional research through grants to major medical institutions across the country. Much of this resea...
The prognosis for individuals with Coffin-Lowry syndrome varies depending on the severity of symptoms. Early intervention may improve the outlook for patients. Life span is reduced in some individuals with Coffin-Lowry syndrome.
Spinal muscular atrophy (SMA) is a genetic disease that attacks nerve cells, called motor neurons, in the spinal cord. These cells communicate with your voluntary muscles - the ones you can control, like in your arms and legs. As the neurons die, the muscles weaken. This can affect walking, crawling, breathing, swallow...
Penicillin, administered intravenously, is the treatment of choice. Associated pain can be treated with opiates, valproate, or carbamazepine. Patients may also require physical or rehabilitative therapy to deal with muscle wasting and weakness. Preventive treatment for those who come into sexual contact with an individ...
MECP2-related severe neonatal encephalopathy is likely a rare condition. Twenty to 30 affected males have been reported in the scientific literature.
What causes mitochondrial complex II deficiency? Many genes must work together to ensure that the enzyme, complex II (succinate dehydrogenase), can perform its job normally in the body. Changes in the SDHA, SDHB, SDHC, SDHD, SDHAF1, and SDHAF2 genes can all potentially cause complex II deficiency. Complex II deficiency...
How might non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency be treated? In some cases, people affected by non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (NCAH) may not require any treatment. Many are asymptomatic throughout their lives, although symptoms may develo...
Anaplastic astrocytoma is a rare, cancerous (malignant) type of brain tumor that arises from star-shaped brain cells called astrocytes. These cells surround and protect nerve cells in the brain and spinal cord. An anaplastic astrocytoma usually develops slowly over time, but may develop rapidly. Signs and symptoms vary...
Lattice corneal dystrophy type II is caused by mutations in the GSN gene. This gene provides instructions for making a protein called gelsolin. This protein is found throughout the body and helps regulate the formation of the network of protein filaments that gives structure to cells (the cytoskeleton). Mutations that ...
The prognosis for most individuals with piriformis syndrome is good. Once symptoms of the disorder are addressed, individuals can usually resume their normal activities. In some cases, exercise regimens may need to be modified in order to reduce the likelihood of recurrence or worsening.
Bjrnstad syndrome is caused by mutations in the BCS1L gene. The protein produced from this gene is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. In mitochondria, the BCS1L protein plays a role in oxidative phosphorylation, which is a multistep process t...
When associated with COL2A1 gene mutations, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered COL2A1 gene in each cell is sufficient to cause the disorder. Most COL2A1-associated cases result from new mutations in the gene and occur in people with no history of the disord...
The liver is the bodys largest internal organ. The liver is called the bodys metabolic factory because of the important role it plays in metabolismthe way cells change food into energy after food is digested and absorbed into the blood. The liver has many important functions, including - taking up, sto...
The NINDS, a component of the National Institutes of Health within the U.S. Department of Health and Human Services, vigorously pursues a research program seeking new treatments to reduce and prevent pain and nerve damage.
Milroy disease is a condition that affects the normal function of the lymphatic system. The lymphatic system produces and transports fluids and immune cells throughout the body. Impaired transport with accumulation of lymph fluid can cause swelling (lymphedema). Individuals with Milroy disease typically have lymphedema...
Cockayne syndrome is a rare condition which causes short stature, premature aging (progeria), severe photosensitivity, and moderate to severe learning delay. This syndrome also includes failure to thrive in the newborn, microcephaly, and impaired nervous system development. Other symptoms may include hearing loss, toot...
Mutations in the IDUA gene cause MPS I. The IDUA gene provides instructions for producing an enzyme that is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the IDUA gene reduce...
Hyper IgM syndrome is a type of primary immunodeficiency syndrome. Primary immunodeficiency occurs when part of a persons immune system is missing or does not work correctly. The bodies of people with primary immunodeficiency cant get rid of germs or protect themselves from new germs as well as they should. Primary imm...
These resources address the diagnosis or management of ethylmalonic encephalopathy: - Baby's First Test - Genetic Testing Registry: Ethylmalonic encephalopathy - MedlinePlus Encyclopedia: Skin discoloration - bluish These resources from MedlinePlus offer information about the diagnosis and management of various he...
These resources address the diagnosis or management of cytogenetically normal acute myeloid leukemia: - Fred Hutchinson Cancer Research Center - National Cancer Institute: Acute Myeloid Leukemia Treatment - St. Jude Children's Research Hospital These resources from MedlinePlus offer information about the diagnosis...
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
What causes megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome? The cause of MPPH syndrome is unknown. Infection during pregnancy or fetal accident is thought to be unlikely.
These resources address the diagnosis or management of lissencephaly with cerebellar hypoplasia: - Genetic Testing Registry: Lissencephaly 2 - Genetic Testing Registry: Lissencephaly 3 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic T...
Summary : Most packaged foods in the U.S. have food labels. On every food label you will see - Serving size, number of servings, and number of calories per serving - Information on the amount of dietary fat, cholesterol, dietary fiber, dietary sodium, carbohydrates, dietary proteins, vitamins, and minerals in...
Key Points - Nasopharyngeal cancer is a disease in which malignant (cancer) cells form in the tissues of the nasopharynx. - Ethnic background and being exposed to the Epstein-Barr virus can affect the risk of nasopharyngeal cancer. - Signs of nasopharyngeal cancer include trouble breathing, s...
Your jaw is a set of bones that holds your teeth. It consists of two main parts. The upper part is the maxilla. It doesn't move. The moveable lower part is called the mandible. You move it when you talk or chew. The two halves of the mandible meet at your chin. The joint where the mandible meets your skull is the tempo...
Your rotator cuff is located in your shoulder area. It is made of muscles and tendons. It helps your shoulder to move and stay stable. Problems with the rotator cuff are common. They include tendinitis, bursitis, and injuries such as tears. Rotator cuff tendons can become inflamed from frequent use or aging. Sometim...
These resources address the diagnosis or management of alpha-mannosidosis: - Gene Review: Gene Review: Alpha-Mannosidosis - Genetic Testing Registry: Deficiency of alpha-mannosidase These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Test...
How might McCune Albright syndrome be treated? Although there is no cure for McCune Albright syndrome (MAS), drug treatments may help some of the endocrine symptoms, and surgery can help repair some of the bone problems. Generally, treatment depends on what tissues are affected as well as the severity. Surgery may be n...
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of rhizomelic chondrodysplasia punctata: - Gene Review: Gene Review: Rhizomelic Chondrodysplasia Punctata Type 1 - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 1 - Genetic Testing Registry: Rhizomelic chondrodysplasia punctata type 2 - Genet...
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system, and to use that knowledge to reduce the burden of neurological disease. The NINDS pursues a vigorous program of research aimed at preventing and treating disorders that...
Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. This disorder affects about 1 in 1,500 to 3,500 individuals with European ancestry. It is uncommon in people of Asian descent. Many individuals with alpha-1 antitrypsin deficiency are likely undiagnosed, particularly people with a...
Overall, an estimated 1 in 20,000 people worldwide are born with oculocutaneous albinism. The condition affects people in many ethnic groups and geographical regions. Types 1 and 2 are the most common forms of this condition; types 3 and 4 are less common. Type 2 occurs more frequently in African Americans, some Native...
Crohn's disease is a chronic, or long lasting, disease that causes inflammationirritation or swellingin the gastrointestinal (GI) tract. Most commonly, Crohn's affects the small intestine and the beginning of the large intestine. However, the disease can affect any part of the GI tract, from the mouth to the anus. ...
What causes retroperitoneal fibrosis? The cause of retroperitoneal fibrosis is unknown in many cases (idiopathic). Some cases occur in association with other factors, including: Asbestos exposure Smoking Neoplasms (tumor) Infections Trauma Radiotherapy Surgery Use of certain drugs
What are the signs and symptoms of Corneal endothelial dystrophy type 2? The Human Phenotype Ontology provides the following list of signs and symptoms for Corneal endothelial dystrophy type 2. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can...
These resources address the diagnosis or management of X-linked congenital stationary night blindness: - American Optometric Association: Infant Vision - Gene Review: Gene Review: X-Linked Congenital Stationary Night Blindness - Genetic Testing Registry: Congenital stationary night blindness - Genetic Testing Regis...
The National Institute of Neurological Disorders and Stroke (NINDS) conducts MJD research in its laboratories at the National Institutes of Health (NIH) and also supports MJD research through grants to major medical institutions across the country. Ongoing research includes studies to better understand the genetic, mol...
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
ADNFLE appears to be an uncommon form of epilepsy; its prevalence is unknown. This condition has been reported in more than 100 families worldwide.
What causes cryptogenic organizing pneumonia? The underlying cause of cryptogenic organizing pneumonia (COP) is unknown (idiopathic). Organizing pneumonia is specifically diagnosed as COP when, among other characteristics, no definite cause for the organizing pneumonia is found. In other words, any known cause for the ...
Bell's palsy is the most common cause of facial paralysis. It usually affects just one side of the face. Symptoms appear suddenly and are at their worst about 48 hours after they start. They can range from mild to severe and include - Twitching - Weakness - Paralysis - Drooping eyelid or corner of mouth ...
Diverticular disease is a condition that occurs when a person has problems from small pouches, or sacs, that have formed and pushed outward through weak spots in the colon wall. Each pouch is called a diverticulum. Multiple pouches are called diverticula. The colon is part of the large intestine. The l...
In most people with polymicrogyria, the cause of the condition is unknown. However, researchers have identified several environmental and genetic factors that can be responsible for the disorder. Environmental causes of polymicrogyria include certain infections during pregnancy and a lack of oxygen to the fetus (intrau...
- Pyelonephritis is a type of urinary tract infection that affects one or both kidneys. - Pyelonephritis is caused by a bacterium or virus infecting the kidneys. Though many bacteria and viruses can cause pyelonephritis, the bacterium Escherichia coli is often the cause. Bacteria and viruses can move to the kidneys fr...
ESS is not a life-threatening condition. Most often, and particularly among those with primary ESS, the disorder does not cause health problems and does not affect life expectancy.
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
What causes pseudohypoaldosteronism type 2? Pseudohypoaldosteronism type 2 is caused by mutations in either the WNK1 or WNK4 genes. Mutations in these genes cause salt retention and impaired excretion of potassium and acid, leading to high blood pressure, hyperkalemia (high levels of potassium), and metabolic acidosis.
Mutations in the CACNA1C gene are responsible for all reported cases of Timothy syndrome. This gene provides instructions for making a protein that acts as a channel across cell membranes. This channel, known as CaV1.2, is one of several channels that transport positively charged calcium atoms (calcium ions) into cells...
Dry AMD occurs when the light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye. As dry AMD gets worse, you may see a blurred spot in the center of your vision. Over time, as less of the macula functions, central vision in the affected eye can be lost. If you have vi...
Acute Bronchitis Infections or lung irritants cause acute bronchitis. The same viruses that cause colds and the flu are the most common cause of acute bronchitis. Sometimes bacteria can cause the condition. Certain substances can irritate your lungs and airways and raise your risk for ...
Glutaric acidemia type I is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these a...
Most patients with back pain recover without residual functional loss, but individuals should contact a doctor if there is not a noticeable reduction in pain and inflammation after 72 hours of self-care. Recurring back pain resulting from improper body mechanics or other nontraumatic causes is often preventable. Engagi...
What are the signs and symptoms of BRCA2 hereditary breast and ovarian cancer syndrome? The Human Phenotype Ontology provides the following list of signs and symptoms for BRCA2 hereditary breast and ovarian cancer syndrome. If the information is available, the table below includes how often the symptom is seen in peopl...
The precise incidence of thrombotic thrombocytopenic purpura is unknown. Researchers estimate that, depending on geographic location, the condition affects 1.7 to 11 per million people each year in the United States. For unknown reasons, the disorder occurs more frequently in women than in men. The acquired form of thr...
Branchiootorenal syndrome is characterized by birth defects or anomalies of tissues in the neck, malformations of the external ear, hearing loss, and kidney malformations. Symptom and symptom severity can vary greatly from person to person. It can be caused by mutations in the EYA1, SIX1, or SIX5 genes. It is passed th...
How is pyruvate kinase deficiency inherited? Pyruvate kinase deficiency is inherited in an autosomal recessive fashion, which means that a child must inherit a gene with a disease-causing mutation from both parents to develop the disorder. The gene that causes pyruvate kinase deficiency is called the PKLR gene that is ...
Fanconi Bickel syndrome (FBS) is a rare glycogen storage disease characterized by glycogen accumulation in the liver and kidneys; severe renal tubular dysfunction; and impaired glucose and galactose metabolism. Signs and symptoms begin in the first few months of life and include failure to thrive, excessive urination (...
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Notalgia paresthetica is a common chronic, localized itch, that usually affects patches of skin on the upper back. Occasionally be more widespread and involve other parts of the back, the shoulders and upper chest. People feel both the sensation of an itch and paresthesia (a sensation of tingling, pricking, or numbness...
Childhood hypophosphatasia is a form of hypophosphatasia, a rare condition that affects the bones. Childhood hypophosphatasia, specifically, is generally diagnosed when the condition develops after six months of age but before adulthood. Signs and symptoms vary but may include delayed motor milestones; low bone mineral...
What causes Friedreich ataxia? Friedreich ataxia is caused by mutations in the FXN gene. This gene provides instructions for making a protein called frataxin. One region of the FXN gene contains a segment of DNA known as a GAA trinucleotide repeat. This segment is made up of a series of three DNA building blocks (one g...
Lewy bodies are unusual deposits or clumps of the brain protein alpha-synuclein, along with other proteins, which are seen upon microscopic examination of the brain. Many brain cells of people with Parkinson's disease contain Lewy bodies. Researchers do not yet know why Lewy bodies form or what role they play in the de...
Until recently, an accurate protein measurement required a 24-hour urine collection. In a 24-hour collection, the patient urinates into a container, which is kept refrigerated between trips to the bathroom. The patient is instructed to begin collecting urine after the first trip to the bathroom in the morning. Every dr...
Glutathione synthetase deficiency is very rare. This disorder has been described in more than 70 people worldwide.
The prevalence of pontocerebellar hypoplasia is unknown, although most forms of the disorder appear to be very rare.
Spina bifida (SB) is a neural tube defect (a disorder involving incomplete development of the brain, spinal cord, and/or their protective coverings) caused by the failure of the fetus's spine to close properly during the first month of pregnancy. Infants born with SB sometimes have an open lesion on their spine where s...
The ovaries are a pair of organs that women have. They are located in the pelvis, one on each side of the uterus. Each ovary is about the size and shape of an almond. The ovaries produce a woman's eggs. If an egg is fertilized by a sperm, a pregnancy can result. Ovaries also make the female hormones estrogen and pro...
Mutations in at least four genes increase the risk of developing the different types of hereditary paraganglioma-pheochromocytoma. Mutations in the SDHD gene predispose an individual to hereditary paraganglioma-pheochromocytoma type 1; mutations in the SDHAF2 gene predispose to type 2; mutations in the SDHC gene predis...
Taste is the ability to detect different sensations in the mouth, such as sweet or salty. It is part of your body's chemical sensing system. Taste combines with other oral sensations, such as texture, spiciness, temperature, and aroma to produce what is commonly referred to as flavor.