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nord_85_5 | Diagnosis of Aniridia Cerebellar Ataxia Mental Deficiency | The diagnosis of aniridia, cerebellar ataxia and mental deficiency may be made at birth if the newborn (neonate) presents with partial absence of the iris in association with hypotonia. Although partial aniridia may be obvious at birth, the other symptoms may not become apparent until later in the child's development. Therefore, the disorder usually is not diagnosed until early childhood, based upon a thorough clinical evaluation, a detailed patient history, specialized laboratory tests, and advanced imaging techniques.Examination of the eyes using a slit-lamp and an instrument that measures certain angles in the eye (gonioscope), and to reveal any remnants of iris tissue that may be present, help to establish and confirm a diagnosis of partial aniridia. If involuntary movements of the eye (nystagmus) occur in association with aniridia, the ophthalmologist will record eye movements to determine the exact type of nystagmus present.Cerebellar ataxia due to underdevelopment of the cerebellum (cerebellar hypoplasia) may be confirmed by imaging techniques such as CT (computerized tomography) scanning and MRI (magnetic resonance imaging). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of different organs of the body. | Diagnosis of Aniridia Cerebellar Ataxia Mental Deficiency. The diagnosis of aniridia, cerebellar ataxia and mental deficiency may be made at birth if the newborn (neonate) presents with partial absence of the iris in association with hypotonia. Although partial aniridia may be obvious at birth, the other symptoms may not become apparent until later in the child's development. Therefore, the disorder usually is not diagnosed until early childhood, based upon a thorough clinical evaluation, a detailed patient history, specialized laboratory tests, and advanced imaging techniques.Examination of the eyes using a slit-lamp and an instrument that measures certain angles in the eye (gonioscope), and to reveal any remnants of iris tissue that may be present, help to establish and confirm a diagnosis of partial aniridia. If involuntary movements of the eye (nystagmus) occur in association with aniridia, the ophthalmologist will record eye movements to determine the exact type of nystagmus present.Cerebellar ataxia due to underdevelopment of the cerebellum (cerebellar hypoplasia) may be confirmed by imaging techniques such as CT (computerized tomography) scanning and MRI (magnetic resonance imaging). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of different organs of the body. | 85 | Aniridia Cerebellar Ataxia Mental Deficiency |
nord_85_6 | Therapies of Aniridia Cerebellar Ataxia Mental Deficiency | TreatmentThe treatment of ACAMD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat diseases of the eye (ophthalmologists), specialists who assess and correct visual problems with corrective lenses (optometrists), physical therapists, and others may need to work together to ensure a comprehensive approach to treatment.Early intervention is also important in ensuring that affected children with cerebellar ataxia, developmental delays, and mental retardation reach their potential. Special services that may be beneficial to affected children may include physical therapy, special remedial education, speech therapy, and other medical, social, and/or vocational services.Genetic counseling will also be of benefit for affected families. Other treatment is symptomatic and supportive. | Therapies of Aniridia Cerebellar Ataxia Mental Deficiency. TreatmentThe treatment of ACAMD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who diagnose and treat diseases of the eye (ophthalmologists), specialists who assess and correct visual problems with corrective lenses (optometrists), physical therapists, and others may need to work together to ensure a comprehensive approach to treatment.Early intervention is also important in ensuring that affected children with cerebellar ataxia, developmental delays, and mental retardation reach their potential. Special services that may be beneficial to affected children may include physical therapy, special remedial education, speech therapy, and other medical, social, and/or vocational services.Genetic counseling will also be of benefit for affected families. Other treatment is symptomatic and supportive. | 85 | Aniridia Cerebellar Ataxia Mental Deficiency |
nord_86_0 | Overview of Anthrax | Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. It is usually a disease of wild and domestic animals, including cattle, sheep, and goats. However, human infection, while rare, does occur. Human infection usually results from contact with infected animals or their products. However, anthrax has become of interest because of the possibility that a nation or terrorist group might attempt to use it as a weapon of warfare or terrorism. There are three types of anthrax: cutaneous (through the skin), gastrointestinal, and inhalational. | Overview of Anthrax. Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. It is usually a disease of wild and domestic animals, including cattle, sheep, and goats. However, human infection, while rare, does occur. Human infection usually results from contact with infected animals or their products. However, anthrax has become of interest because of the possibility that a nation or terrorist group might attempt to use it as a weapon of warfare or terrorism. There are three types of anthrax: cutaneous (through the skin), gastrointestinal, and inhalational. | 86 | Anthrax |
nord_86_1 | Symptoms of Anthrax | Symptoms usually appear within seven days of exposure, although in some cases the incubation period has been significantly longer than this.Cutaneous anthrax begins with a raised area on the skin that itches (pruritic papule). Usually, this occurs on exposed areas, most often on the arms and hands followed by the face and neck. It resembles an insect bite. This area becomes larger and, within one or two days, develops into an ulcer, surrounded by small blisters containing fluid. A characteristic black, crusty spot develops on the affected skin area later and, after a few weeks, begins to loosen and ultimately falls off, leaving a scar. The course of these events is so characteristic that the diagnosis is not often missed by physicians familiar with the disease, even though it is rare.Gastrointestinal anthrax can present as either intestinal or throat and pharynx (oropharyngeal) disease. The symptoms for intestinal infection include fever, nausea, abdominal pain, vomiting, and anorexia. As the disease progresses, there may also be vomiting of blood, bloody diarrhea, toxemia, shock and a bluish tinge to the skin and mucous membranes (cyanosis). Symptoms for oropharyngeal illness may include fever, sore throat, difficulty in swallowing (dysphagia), collection of fluid (edema) in the tissues of the throat, and swelling of the lymph nodes.Inhalational anthrax typically begins with one to three days of fatigue, low-grade fever, and dry cough. These symptoms, typical of a mild upper respiratory tract infection, may be accompanied by an ache of feeling of heaviness in the chest and the area just below the chest. Following this relatively mild onset, there will be a period of more intense illness characterized by high fever, elevation of the pulse and respiratory rate, heavy perspiration (profuse diaphoresis), and difficult or labored breathing (dyspnea). | Symptoms of Anthrax. Symptoms usually appear within seven days of exposure, although in some cases the incubation period has been significantly longer than this.Cutaneous anthrax begins with a raised area on the skin that itches (pruritic papule). Usually, this occurs on exposed areas, most often on the arms and hands followed by the face and neck. It resembles an insect bite. This area becomes larger and, within one or two days, develops into an ulcer, surrounded by small blisters containing fluid. A characteristic black, crusty spot develops on the affected skin area later and, after a few weeks, begins to loosen and ultimately falls off, leaving a scar. The course of these events is so characteristic that the diagnosis is not often missed by physicians familiar with the disease, even though it is rare.Gastrointestinal anthrax can present as either intestinal or throat and pharynx (oropharyngeal) disease. The symptoms for intestinal infection include fever, nausea, abdominal pain, vomiting, and anorexia. As the disease progresses, there may also be vomiting of blood, bloody diarrhea, toxemia, shock and a bluish tinge to the skin and mucous membranes (cyanosis). Symptoms for oropharyngeal illness may include fever, sore throat, difficulty in swallowing (dysphagia), collection of fluid (edema) in the tissues of the throat, and swelling of the lymph nodes.Inhalational anthrax typically begins with one to three days of fatigue, low-grade fever, and dry cough. These symptoms, typical of a mild upper respiratory tract infection, may be accompanied by an ache of feeling of heaviness in the chest and the area just below the chest. Following this relatively mild onset, there will be a period of more intense illness characterized by high fever, elevation of the pulse and respiratory rate, heavy perspiration (profuse diaphoresis), and difficult or labored breathing (dyspnea). | 86 | Anthrax |
nord_86_2 | Causes of Anthrax | Anthrax is primarily a disease of animals, specifically herbivores such as cattle, goats, and sheep. They contract the disease after coming into contact with B. anthracis spores, which are present in the soil around the world. The rare cases when humans are infected typically occur when people come into contact through their occupations with infected animals or when people eat undercooked meat or other products from infected animals. Its occurrence is most likely in developing countries, although animal products imported from those countries may pose a risk.Human infection sometimes results from contact in an industrial setting. In the United States, there have been occasional episodes in industrial settings resulting from, for instance, processing contaminated animal fibers such as goat hair.Infection may also occur among those who work in agricultural jobs. These infections typically occur among people who have had direct contact with animals sick with anthrax or those who have died with the disease.Cutaneous anthrax occurs after spores come into contact with skin that is broken as a result of a wound or lesion. Gastrointestinal anthrax occurs as a result of eating poorly cooked or raw meat from animals that are infected with the disease. Inhalational anthrax occurs as a result of breathing in (inhaling) the spores.There have been no confirmed cases of person-to-person transmission of cutaneous, gastrointestinal, or inhalational anthrax. For this reason, it is believed unnecessary to immunize or treat the family members, friends, or co-workers of those who become ill with anthrax unless it is possible that they have been exposed to the same original source of the infection. | Causes of Anthrax. Anthrax is primarily a disease of animals, specifically herbivores such as cattle, goats, and sheep. They contract the disease after coming into contact with B. anthracis spores, which are present in the soil around the world. The rare cases when humans are infected typically occur when people come into contact through their occupations with infected animals or when people eat undercooked meat or other products from infected animals. Its occurrence is most likely in developing countries, although animal products imported from those countries may pose a risk.Human infection sometimes results from contact in an industrial setting. In the United States, there have been occasional episodes in industrial settings resulting from, for instance, processing contaminated animal fibers such as goat hair.Infection may also occur among those who work in agricultural jobs. These infections typically occur among people who have had direct contact with animals sick with anthrax or those who have died with the disease.Cutaneous anthrax occurs after spores come into contact with skin that is broken as a result of a wound or lesion. Gastrointestinal anthrax occurs as a result of eating poorly cooked or raw meat from animals that are infected with the disease. Inhalational anthrax occurs as a result of breathing in (inhaling) the spores.There have been no confirmed cases of person-to-person transmission of cutaneous, gastrointestinal, or inhalational anthrax. For this reason, it is believed unnecessary to immunize or treat the family members, friends, or co-workers of those who become ill with anthrax unless it is possible that they have been exposed to the same original source of the infection. | 86 | Anthrax |
nord_86_3 | Affects of Anthrax | Anthrax is most common in developing countries. It can be found globally, although the regions of the world with the greatest incidence of agricultural anthrax are South and Central America, Southern and Eastern Europe, Asia, Africa, the Caribbean, and the Middle East.The largest reported agricultural outbreak occurred in Zimbabwe, with more than 10,000 cases reported between 1979 and 1985.In 1979, 79 cases of inhalational anthrax were reported in the area of Sverdlovsk, Russia. Sixty-eight of those cases ultimately were fatal. It is believed that this outbreak was caused by the accidental release of aerosolized anthrax spores from a military laboratory. | Affects of Anthrax. Anthrax is most common in developing countries. It can be found globally, although the regions of the world with the greatest incidence of agricultural anthrax are South and Central America, Southern and Eastern Europe, Asia, Africa, the Caribbean, and the Middle East.The largest reported agricultural outbreak occurred in Zimbabwe, with more than 10,000 cases reported between 1979 and 1985.In 1979, 79 cases of inhalational anthrax were reported in the area of Sverdlovsk, Russia. Sixty-eight of those cases ultimately were fatal. It is believed that this outbreak was caused by the accidental release of aerosolized anthrax spores from a military laboratory. | 86 | Anthrax |
nord_86_4 | Related disorders of Anthrax | Influenza is a common infectious viral disease with symptoms that may appear similar to inhalational anthrax. However, anthrax does not cause runny nose, which is a typical symptom of the common cold and influenza. Also, patients with anthrax appear to have abnormal X-rays, while those with flu and other viruses do not. | Related disorders of Anthrax. Influenza is a common infectious viral disease with symptoms that may appear similar to inhalational anthrax. However, anthrax does not cause runny nose, which is a typical symptom of the common cold and influenza. Also, patients with anthrax appear to have abnormal X-rays, while those with flu and other viruses do not. | 86 | Anthrax |
nord_86_5 | Diagnosis of Anthrax | Cutaneous anthrax may be diagnosed by the characteristic signs, such as the raised area on the skin and detection of the presence of the anthrax bacilli in the area of the lesion. A history of exposure to livestock or other possible animal sources also is important. Gastrointestinal anthrax is more difficult to diagnose. In the first, mild phase of inhalational anthrax, symptoms resemble a common cold or upper respiratory infection. With the sudden onset of the more severe symptoms of the second phase, radiographic examination of the chest may show characteristic changes. | Diagnosis of Anthrax. Cutaneous anthrax may be diagnosed by the characteristic signs, such as the raised area on the skin and detection of the presence of the anthrax bacilli in the area of the lesion. A history of exposure to livestock or other possible animal sources also is important. Gastrointestinal anthrax is more difficult to diagnose. In the first, mild phase of inhalational anthrax, symptoms resemble a common cold or upper respiratory infection. With the sudden onset of the more severe symptoms of the second phase, radiographic examination of the chest may show characteristic changes. | 86 | Anthrax |
nord_86_6 | Therapies of Anthrax | TreatmentAntibiotics, such as penicillin, are used to treat all forms of anthrax. However, to be effective, treatment must be started as soon as possible after exposure. Once symptoms begin, there is a significant decline in the likelihood that treatment will be successful.An antibiotic known as ciprofloxacin (Cipro) was approved in August 2000 by the U.S. Food and Drug Administration for treating people who have been exposed to inhalational anthrax. However, Cipro, too, needs to be taken soon after exposure, and before symptoms begin, to be effective. Taking this or other antibiotics before exposure, as a preventive measure, is not recommended and may cause harm. Before being approved for this purpose, Cipro had been used for several years to treat a variety of infections, including cutaneous anthrax.Once symptoms have begun, antibiotic therapy is rarely successful against the gastrointestinal or inhalational forms of the disease.For more information about antibiotic treatments used for anthrax, you may access the following government web sites:Cipro (Ciprofloxacin): Use by Pregnant and Lactating Women (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm130712.htmDoxycycline: Questions and Answers for Consumers (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm131012.htmDoxycycline (Vibramycin, Monodox, Doryx, Doxy, Atridox, Periodox, Vibra_Tabs): Use by Pregnant and Lactating Women (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm131011.htmDrug Preparedness and Response to Bioterrorism (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm2007083.htmIn 2015, Anthrasil, anthrax immune globulin intravenous (human) was approved to treat patients with inhalational anthrax in combination with appropriate antibacterial drugs. The product is manufactured by Cangene Corporation.In 2016, Anthim injection was approved by the FDA. The injection can be used in a combination with appropriate antibacterial drugs and when alternative therapies are not available. Anthim was developed by Elusy’s Therapeutics, Inc. and the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority. | Therapies of Anthrax. TreatmentAntibiotics, such as penicillin, are used to treat all forms of anthrax. However, to be effective, treatment must be started as soon as possible after exposure. Once symptoms begin, there is a significant decline in the likelihood that treatment will be successful.An antibiotic known as ciprofloxacin (Cipro) was approved in August 2000 by the U.S. Food and Drug Administration for treating people who have been exposed to inhalational anthrax. However, Cipro, too, needs to be taken soon after exposure, and before symptoms begin, to be effective. Taking this or other antibiotics before exposure, as a preventive measure, is not recommended and may cause harm. Before being approved for this purpose, Cipro had been used for several years to treat a variety of infections, including cutaneous anthrax.Once symptoms have begun, antibiotic therapy is rarely successful against the gastrointestinal or inhalational forms of the disease.For more information about antibiotic treatments used for anthrax, you may access the following government web sites:Cipro (Ciprofloxacin): Use by Pregnant and Lactating Women (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm130712.htmDoxycycline: Questions and Answers for Consumers (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm131012.htmDoxycycline (Vibramycin, Monodox, Doryx, Doxy, Atridox, Periodox, Vibra_Tabs): Use by Pregnant and Lactating Women (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm131011.htmDrug Preparedness and Response to Bioterrorism (7/21/2015); http://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm2007083.htmIn 2015, Anthrasil, anthrax immune globulin intravenous (human) was approved to treat patients with inhalational anthrax in combination with appropriate antibacterial drugs. The product is manufactured by Cangene Corporation.In 2016, Anthim injection was approved by the FDA. The injection can be used in a combination with appropriate antibacterial drugs and when alternative therapies are not available. Anthim was developed by Elusy’s Therapeutics, Inc. and the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority. | 86 | Anthrax |
nord_87_0 | Overview of Antiphospholipid Syndrome | Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by recurring blood clots (thromboses). Blood clots can form in any blood vessel of the body. The specific symptoms and severity of APS vary greatly from person to person depending upon the exact location of a blood clot and the organ system affected. APS may occur as an isolated disorder (primary antiphospholipid syndrome) or may occur along with another autoimmune disorder such as systemic lupus erythematosus (secondary antiphospholipid syndrome).APS is characterized by the presence of antiphospholipid antibodies in the body. Antibodies are specialized proteins produced by the body's immune system to fight infection. In individuals with APS, certain antibodies mistakenly attack healthy tissue. In APS, antibodies mistakenly attack certain proteins that bind to phospholipids, which are fat molecules that are involved in the proper function of cell membranes. Phospholipids are found throughout the body. The reason these antibodies attack these proteins and the process by which they cause blood clots to form is not known. | Overview of Antiphospholipid Syndrome. Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by recurring blood clots (thromboses). Blood clots can form in any blood vessel of the body. The specific symptoms and severity of APS vary greatly from person to person depending upon the exact location of a blood clot and the organ system affected. APS may occur as an isolated disorder (primary antiphospholipid syndrome) or may occur along with another autoimmune disorder such as systemic lupus erythematosus (secondary antiphospholipid syndrome).APS is characterized by the presence of antiphospholipid antibodies in the body. Antibodies are specialized proteins produced by the body's immune system to fight infection. In individuals with APS, certain antibodies mistakenly attack healthy tissue. In APS, antibodies mistakenly attack certain proteins that bind to phospholipids, which are fat molecules that are involved in the proper function of cell membranes. Phospholipids are found throughout the body. The reason these antibodies attack these proteins and the process by which they cause blood clots to form is not known. | 87 | Antiphospholipid Syndrome |
nord_87_1 | Symptoms of Antiphospholipid Syndrome | The specific symptoms associated with antiphospholipid syndrome are related to the presence and location of blood clots. Blood clots can form in any blood vessel of the body. Clots are twice as likely to form in vessels that carry blood to the heart (veins) as in vessels that carry blood away from the heart (arteries). Any organ system of the body can become involved. The lower limbs, lungs and brain are affected most often. APS also causes significant complications during pregnancy.The severity of APS varies, ranging from minor blood clots that cause few problems to an extremely rare form (catastrophic APS) in which multiple clots form throughout the body. However, in most cases, blood clots will only develop at one site.When blood clots affect the flow of blood to the brain a variety of issues can development including serious complications such as stroke or stroke-like episodes known as transient ischemic attacks. Less frequently, seizures or unusual shaking or involuntary muscle movements (chorea) may occur.Blood clots in large, deep veins are referred to as deep vein thrombosis (DVT). The most common site of DVT is the legs, which can become painful and swollen. In some cases, a piece of the blood clot may break off, travel in the bloodstream, and become lodged in the lungs. This is referred to as pulmonary embolism. Pulmonary embolism may cause breathlessness, a sudden pain the chest, exhaustion, high blood pressure of the pulmonary arteries, or sudden death.Skin rashes and other skin diseases may occur in people with APS. These include blotchy reddish patches of discolored skin, a condition known as livedo reticularis. In some cases, sores (ulcers) may form on the legs. Lack of blood flow to the extremities can cause loss of living tissue (necrotic gangrene), especially in the fingers or toes.Additional abnormalities that may occur in individuals with APS include clot-like deposits on the valves of the heart (valvular heart disease) which can permanently damage the valves. For example, a potential complication is mitral valve regurgitation (MVR). In MVR, the mitral valve does not shut properly allowing blood to flow backward into the heart. Affected individuals may also experience chest pain (angina) and the possibility of a heart attack (myocardial infarction) at an early age but these problems are not thought to be related to valvular heart disease.Some affected individuals can develop low levels of blood platelets (thrombocytopenia). Thrombocytopenia associated with antiphospholipid antibodies is usually mild and only rarely causes easy or excessive bruising and prolong bleeding episodes. Affected individuals are also at risk for autoimmune hemolytic anemia, a condition characterized by the premature destruction of red blood cells by the immune system.Some individuals have reported symptoms that resemble multiple sclerosis including numbness or a sensation of pins and needles, vision abnormalities such as double vision, and difficulty walking, but it is not known if these problems are related to APS. Some data show an association of APS with cognitive dysfunction, but the mechanism is not known.In women, APS can cause complications during pregnancy including repeated miscarriages, fetal growth delays (intrauterine growth retardation), and preeclampsia. Preeclampsia is a condition characterized by high blood pressure, swelling and protein in the urine. Symptoms associated with preeclampsia vary greatly, but may include headaches, changes in vision, abdominal pain, nausea and vomiting.CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME (CAPS)
Catastrophic antiphospholipid syndrome, also known as CAPS or Asherson's syndrome, is an extremely rare variant of APS in which multiple blood clots affect various organ systems of the body potentially causing life-threatening multi-organ failure. The specific presentation, progression and organs involved vary from person to person. CAPS may develop in a person with primary or secondary APS or in individuals without a previous diagnosis of APS. In some cases, infection, trauma, or surgery appears to trigger the condition. | Symptoms of Antiphospholipid Syndrome. The specific symptoms associated with antiphospholipid syndrome are related to the presence and location of blood clots. Blood clots can form in any blood vessel of the body. Clots are twice as likely to form in vessels that carry blood to the heart (veins) as in vessels that carry blood away from the heart (arteries). Any organ system of the body can become involved. The lower limbs, lungs and brain are affected most often. APS also causes significant complications during pregnancy.The severity of APS varies, ranging from minor blood clots that cause few problems to an extremely rare form (catastrophic APS) in which multiple clots form throughout the body. However, in most cases, blood clots will only develop at one site.When blood clots affect the flow of blood to the brain a variety of issues can development including serious complications such as stroke or stroke-like episodes known as transient ischemic attacks. Less frequently, seizures or unusual shaking or involuntary muscle movements (chorea) may occur.Blood clots in large, deep veins are referred to as deep vein thrombosis (DVT). The most common site of DVT is the legs, which can become painful and swollen. In some cases, a piece of the blood clot may break off, travel in the bloodstream, and become lodged in the lungs. This is referred to as pulmonary embolism. Pulmonary embolism may cause breathlessness, a sudden pain the chest, exhaustion, high blood pressure of the pulmonary arteries, or sudden death.Skin rashes and other skin diseases may occur in people with APS. These include blotchy reddish patches of discolored skin, a condition known as livedo reticularis. In some cases, sores (ulcers) may form on the legs. Lack of blood flow to the extremities can cause loss of living tissue (necrotic gangrene), especially in the fingers or toes.Additional abnormalities that may occur in individuals with APS include clot-like deposits on the valves of the heart (valvular heart disease) which can permanently damage the valves. For example, a potential complication is mitral valve regurgitation (MVR). In MVR, the mitral valve does not shut properly allowing blood to flow backward into the heart. Affected individuals may also experience chest pain (angina) and the possibility of a heart attack (myocardial infarction) at an early age but these problems are not thought to be related to valvular heart disease.Some affected individuals can develop low levels of blood platelets (thrombocytopenia). Thrombocytopenia associated with antiphospholipid antibodies is usually mild and only rarely causes easy or excessive bruising and prolong bleeding episodes. Affected individuals are also at risk for autoimmune hemolytic anemia, a condition characterized by the premature destruction of red blood cells by the immune system.Some individuals have reported symptoms that resemble multiple sclerosis including numbness or a sensation of pins and needles, vision abnormalities such as double vision, and difficulty walking, but it is not known if these problems are related to APS. Some data show an association of APS with cognitive dysfunction, but the mechanism is not known.In women, APS can cause complications during pregnancy including repeated miscarriages, fetal growth delays (intrauterine growth retardation), and preeclampsia. Preeclampsia is a condition characterized by high blood pressure, swelling and protein in the urine. Symptoms associated with preeclampsia vary greatly, but may include headaches, changes in vision, abdominal pain, nausea and vomiting.CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME (CAPS)
Catastrophic antiphospholipid syndrome, also known as CAPS or Asherson's syndrome, is an extremely rare variant of APS in which multiple blood clots affect various organ systems of the body potentially causing life-threatening multi-organ failure. The specific presentation, progression and organs involved vary from person to person. CAPS may develop in a person with primary or secondary APS or in individuals without a previous diagnosis of APS. In some cases, infection, trauma, or surgery appears to trigger the condition. | 87 | Antiphospholipid Syndrome |
nord_87_2 | Causes of Antiphospholipid Syndrome | Antiphospholipid syndrome is an autoimmune disorder of unknown cause. Autoimmune disorders are caused when the body natural defenses (antibodies, lymphocytes, etc.) against invading organisms attack perfectly healthy tissue. Researchers believe that multiple factors including genetic and environmental factors play a role in the development of APS. In rare cases, APS has run in families suggesting that a genetic predisposition to developing the disorder may exist.The antibodies that are present in APS are known as antiphospholipid antibodies. These antibodies were originally thought to attack phospholipids, fatty molecules that are a normal part of cell membranes found throughout the body. However, researchers now know that these antibodies mostly target certain blood proteins that bind to phospholipids. The two most common proteins affected are beta-2-glycoprotein I and prothrombin. The exact mechanism by which these antiphospholipid antibodies eventually lead to the development of blood clots is not known. | Causes of Antiphospholipid Syndrome. Antiphospholipid syndrome is an autoimmune disorder of unknown cause. Autoimmune disorders are caused when the body natural defenses (antibodies, lymphocytes, etc.) against invading organisms attack perfectly healthy tissue. Researchers believe that multiple factors including genetic and environmental factors play a role in the development of APS. In rare cases, APS has run in families suggesting that a genetic predisposition to developing the disorder may exist.The antibodies that are present in APS are known as antiphospholipid antibodies. These antibodies were originally thought to attack phospholipids, fatty molecules that are a normal part of cell membranes found throughout the body. However, researchers now know that these antibodies mostly target certain blood proteins that bind to phospholipids. The two most common proteins affected are beta-2-glycoprotein I and prothrombin. The exact mechanism by which these antiphospholipid antibodies eventually lead to the development of blood clots is not known. | 87 | Antiphospholipid Syndrome |
nord_87_3 | Affects of Antiphospholipid Syndrome | APS affects males and females, but a large percentage of primary APS patients are women with recurrent pregnancy loss. Some estimates suggest that 1 in 5 cases of recurrent miscarriages or deep vein thromboses are due to APS. As many as one-third of cases of stroke in people under 50 years of age may be due to APS. Secondary APS occurs mainly in lupus, and about 90% of lupus patients are female. | Affects of Antiphospholipid Syndrome. APS affects males and females, but a large percentage of primary APS patients are women with recurrent pregnancy loss. Some estimates suggest that 1 in 5 cases of recurrent miscarriages or deep vein thromboses are due to APS. As many as one-third of cases of stroke in people under 50 years of age may be due to APS. Secondary APS occurs mainly in lupus, and about 90% of lupus patients are female. | 87 | Antiphospholipid Syndrome |
nord_87_4 | Related disorders of Antiphospholipid Syndrome | Symptoms of the following disorders can be similar to those of antiphospholipid syndrome. Comparisons may be useful for a differential diagnosis.Several rare genetic disorders are characterized by the formation of blood clots (thromboses). These disorders may be collectively referred as the thrombophilias and include protein C deficiency, protein S deficiency, antithrombin III deficiency, and factor V Leiden. (For more information on these disorders, contact the National Alliance for Thrombosis and Thrombophilia.)Some individuals with APS may be misdiagnosed as having multiple sclerosis (MS) because of the development of similar neurological symptoms. Multiple sclerosis is a chronic disease of the brain and spinal cord (central nervous system) that may be progressive, relapsing and remitting, or stable. The pathology of MS consists of small lesions called plaques that may form randomly throughout the brain and spinal cord. These patches prevent proper transmission of nervous system signals and thus result in a variety of symptoms including eye abnormalities, impairment of speech, and numbness or tingling sensation in the limbs and difficulty walking. The exact cause of multiple sclerosis is unknown. (For more information on this disorder choose “Multiple Sclerosis” as your search term in the Rare Disease Database.)Lupus (systemic lupus erythematosus) is a chronic, inflammatory autoimmune disorder that can affect various organ systems. In autoimmune disorders, the body’s own immune system mistakenly attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus, the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. The initial symptoms may include arthritis, skin rashes, fatigue, fever, pleurisy, and weight loss. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. | Related disorders of Antiphospholipid Syndrome. Symptoms of the following disorders can be similar to those of antiphospholipid syndrome. Comparisons may be useful for a differential diagnosis.Several rare genetic disorders are characterized by the formation of blood clots (thromboses). These disorders may be collectively referred as the thrombophilias and include protein C deficiency, protein S deficiency, antithrombin III deficiency, and factor V Leiden. (For more information on these disorders, contact the National Alliance for Thrombosis and Thrombophilia.)Some individuals with APS may be misdiagnosed as having multiple sclerosis (MS) because of the development of similar neurological symptoms. Multiple sclerosis is a chronic disease of the brain and spinal cord (central nervous system) that may be progressive, relapsing and remitting, or stable. The pathology of MS consists of small lesions called plaques that may form randomly throughout the brain and spinal cord. These patches prevent proper transmission of nervous system signals and thus result in a variety of symptoms including eye abnormalities, impairment of speech, and numbness or tingling sensation in the limbs and difficulty walking. The exact cause of multiple sclerosis is unknown. (For more information on this disorder choose “Multiple Sclerosis” as your search term in the Rare Disease Database.)Lupus (systemic lupus erythematosus) is a chronic, inflammatory autoimmune disorder that can affect various organ systems. In autoimmune disorders, the body’s own immune system mistakenly attacks healthy cells and tissues causing inflammation and malfunction of various organ systems. In lupus, the organ systems most often involved include the skin, kidneys, blood and joints. Many different symptoms are associated with lupus, and most affected individuals do not experience all of the symptoms. The initial symptoms may include arthritis, skin rashes, fatigue, fever, pleurisy, and weight loss. In some cases, lupus may be a mild disorder affecting only a few organ systems. In other cases, it may result in serious complications. | 87 | Antiphospholipid Syndrome |
nord_87_5 | Diagnosis of Antiphospholipid Syndrome | A diagnosis of antiphospholipid syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic physical findings (at least one blood clot or clinical finding), and a variety of tests including simple blood tests.The most common blood tests used to detect antiphospholipid antibodies are anticardiolipin antibody immunoassays (which, despite the name, detect mainly antibodies to beta-2-glycoprotein I), anti-beta-2-glycoprotein antibody immunoassays, and lupus anticoagulant tests (coagulation assays that detect subsets of anti-beta-2-glycoprotein I antibodies and anti-prothrombin antibodies). Positive tests should be repeated because antiphospholipid antibodies can be present in short intervals (transiently) due to other reasons such as infection or drug use. Borderline negative tests may need to be repeated because individuals with APS have initially tested negative for the antiphospholipid antibodies. | Diagnosis of Antiphospholipid Syndrome. A diagnosis of antiphospholipid syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic physical findings (at least one blood clot or clinical finding), and a variety of tests including simple blood tests.The most common blood tests used to detect antiphospholipid antibodies are anticardiolipin antibody immunoassays (which, despite the name, detect mainly antibodies to beta-2-glycoprotein I), anti-beta-2-glycoprotein antibody immunoassays, and lupus anticoagulant tests (coagulation assays that detect subsets of anti-beta-2-glycoprotein I antibodies and anti-prothrombin antibodies). Positive tests should be repeated because antiphospholipid antibodies can be present in short intervals (transiently) due to other reasons such as infection or drug use. Borderline negative tests may need to be repeated because individuals with APS have initially tested negative for the antiphospholipid antibodies. | 87 | Antiphospholipid Syndrome |
nord_87_6 | Therapies of Antiphospholipid Syndrome | TreatmentIndividuals with APS who do not have symptoms may not require treatment. Some individuals may undergo preventative (prophylaxis) therapy to avoid blood clots from forming. For many individuals, daily treatment with aspirin (which thin the bloods and prevents blood clots) may be all that is needed.Individuals with a history of thrombosis may be treated with drugs that preventing clotting by thinning the blood. These drugs are often referred to as anticoagulants and may include heparin and warfarin (Coumadin). New oral blood thinners (dabigatran, rivaroxaban, and apixaban) have recently been approved to treat other blood clotting conditions. Studies are needed to determine whether these drugs are appropriate for preventing recurrent blood clots in patients with APS. Individuals with repeated thrombotic events may require lifelong anticoagulant therapy.Importantly, affected individuals are strongly encouraged to avoid or reduce risk factors that increase the risk of a blood clot forming. Such risks include smoking, the use of oral contraceptives, high blood pressure (hypertension), or diabetes. During pregnancy, women at a high risk for pregnancy loss are treated with heparin, sometimes in combination with low dose aspirin.
In some cases, heart valve damage may be severe and require surgical replacement. | Therapies of Antiphospholipid Syndrome. TreatmentIndividuals with APS who do not have symptoms may not require treatment. Some individuals may undergo preventative (prophylaxis) therapy to avoid blood clots from forming. For many individuals, daily treatment with aspirin (which thin the bloods and prevents blood clots) may be all that is needed.Individuals with a history of thrombosis may be treated with drugs that preventing clotting by thinning the blood. These drugs are often referred to as anticoagulants and may include heparin and warfarin (Coumadin). New oral blood thinners (dabigatran, rivaroxaban, and apixaban) have recently been approved to treat other blood clotting conditions. Studies are needed to determine whether these drugs are appropriate for preventing recurrent blood clots in patients with APS. Individuals with repeated thrombotic events may require lifelong anticoagulant therapy.Importantly, affected individuals are strongly encouraged to avoid or reduce risk factors that increase the risk of a blood clot forming. Such risks include smoking, the use of oral contraceptives, high blood pressure (hypertension), or diabetes. During pregnancy, women at a high risk for pregnancy loss are treated with heparin, sometimes in combination with low dose aspirin.
In some cases, heart valve damage may be severe and require surgical replacement. | 87 | Antiphospholipid Syndrome |
nord_88_0 | Overview of Antisynthetase Syndrome | Antisynthetase syndrome is a rare, chronic disorder that can affect multiple systems of the body. The disorder is immune-mediated, which means there is inflammation resulting from abnormal functioning of the immune system and the presence of specific autoantibodies that target specific proteins in the body. The symptoms and severity of the disorder can vary greatly among affected individuals. Common symptoms include inflammation of the muscles (myositis), inflammation of several joints (polyarthritis), interstitial lung disease and thickening and cracking (fissuring) and discoloration of the skin of the fingers, called mechanic’s hands). Some individuals develop pain and numbness or a prickly feeling in the fingers and toes in response to cold (Raynaud phenomenon). During a Raynaud episode, the fingers or toes may turn white or blue.Affected individuals can also have nonspecific symptoms like fatigue, unexplained fevers and unintended weight loss. The exact, underlying cause is not fully understood, but some genetic and environmental risk factors have been identified. Antisynthetase syndrome sometimes occurs along with other conditions such as uncommon inflammatory muscle diseases like dermatomyositis or polymyositis. | Overview of Antisynthetase Syndrome. Antisynthetase syndrome is a rare, chronic disorder that can affect multiple systems of the body. The disorder is immune-mediated, which means there is inflammation resulting from abnormal functioning of the immune system and the presence of specific autoantibodies that target specific proteins in the body. The symptoms and severity of the disorder can vary greatly among affected individuals. Common symptoms include inflammation of the muscles (myositis), inflammation of several joints (polyarthritis), interstitial lung disease and thickening and cracking (fissuring) and discoloration of the skin of the fingers, called mechanic’s hands). Some individuals develop pain and numbness or a prickly feeling in the fingers and toes in response to cold (Raynaud phenomenon). During a Raynaud episode, the fingers or toes may turn white or blue.Affected individuals can also have nonspecific symptoms like fatigue, unexplained fevers and unintended weight loss. The exact, underlying cause is not fully understood, but some genetic and environmental risk factors have been identified. Antisynthetase syndrome sometimes occurs along with other conditions such as uncommon inflammatory muscle diseases like dermatomyositis or polymyositis. | 88 | Antisynthetase Syndrome |
nord_88_1 | Symptoms of Antisynthetase Syndrome | The signs and symptoms can vary greatly from one person to another. Every person is unique and how the disorder will affect them can be very different. Symptoms can develop rapidly. Affected individuals will usually not have all of the symptoms discussed below. For example, some affected individuals will have little muscle involvement, but prominent signs of lung disease. Muscle disease, interstitial lung disease and arthritis are generally considered the three main symptoms of this disorder (the classic triad), but they may not develop at the same time.Antisynthetase syndrome can affect the muscles. Muscle inflammation (myositis), muscle pain (myalgia) and muscle stiffness is common. These abnormalities can lead to muscle weakness. Inflammation of several joints of the body (polyarthritis) may also occur. Polyarthritis is associated with pain and stiffness of the affected joints. The surrounding bone is usually not affected (non-erosive arthritis).Some individuals develop interstitial lung disease, which is characterized by progressive inflammation and scarring of the lungs, particularly of the tissue and space around the tiny air sacs, or alveoli. This area is called the interstitium. This can lead to shortness of breath and coughing. In some instances, progressive damage to the lungs can lead to respiratory insufficiency (when the lungs cannot deliver sufficient levels of oxygen to the body) requiring oxygen treatment and, eventually, life-threatening respiratory failure.Nonspecific symptoms can also occur including unexplained fevers, fatigue, loss of appetite, unintended weight loss, difficulty swallowing (dysphagia) and skin rashes including a heliotropic rash, a distinctive reddish-purple rash on the upper eyelid or across the cheeks and bridge of the nose in a ‘butterfly’ pattern. | Symptoms of Antisynthetase Syndrome. The signs and symptoms can vary greatly from one person to another. Every person is unique and how the disorder will affect them can be very different. Symptoms can develop rapidly. Affected individuals will usually not have all of the symptoms discussed below. For example, some affected individuals will have little muscle involvement, but prominent signs of lung disease. Muscle disease, interstitial lung disease and arthritis are generally considered the three main symptoms of this disorder (the classic triad), but they may not develop at the same time.Antisynthetase syndrome can affect the muscles. Muscle inflammation (myositis), muscle pain (myalgia) and muscle stiffness is common. These abnormalities can lead to muscle weakness. Inflammation of several joints of the body (polyarthritis) may also occur. Polyarthritis is associated with pain and stiffness of the affected joints. The surrounding bone is usually not affected (non-erosive arthritis).Some individuals develop interstitial lung disease, which is characterized by progressive inflammation and scarring of the lungs, particularly of the tissue and space around the tiny air sacs, or alveoli. This area is called the interstitium. This can lead to shortness of breath and coughing. In some instances, progressive damage to the lungs can lead to respiratory insufficiency (when the lungs cannot deliver sufficient levels of oxygen to the body) requiring oxygen treatment and, eventually, life-threatening respiratory failure.Nonspecific symptoms can also occur including unexplained fevers, fatigue, loss of appetite, unintended weight loss, difficulty swallowing (dysphagia) and skin rashes including a heliotropic rash, a distinctive reddish-purple rash on the upper eyelid or across the cheeks and bridge of the nose in a ‘butterfly’ pattern. | 88 | Antisynthetase Syndrome |
nord_88_2 | Causes of Antisynthetase Syndrome | The exact cause of antisynthetase syndrome is not fully understood. Affected individuals have autoantibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Autoantibodies are antibodies that mistakenly attack healthy tissue. In antisynthetase syndrome, affected individuals have autoantibodies that target certain enzymes in the body called aminoacyl-tRNA synthetases. Enzymes are specialized proteins that help to bring about specific biochemical reactions in the body and aminoacyl-tRNA synthetases help to regulate the production of other proteins and are important for the overall health and function of the body. Researches do not know why these autoantibodies target aminoacyl-tRNA synthetases. Not every person who develops these autoantibodies will go on to develop symptoms of antisynthetase syndrome.The exact role these autoantibodies play in the development of antisynthetase syndrome is not fully understood. The autoantibodies that have identified in this disorder include anti-Jo1, anti-EJ, anti-OJ, anti-PL7, anti-PL12, anti-SC, anti-KS, anti-JS, anti-HA, anti-YRS, anti-tryptophanyl and anti-Zo, and each of these target a different aminoacyl-tRNA synthetase. Anti-Jo1 is the most common autoantibody in individuals with antisynthetase syndrome.Some autoantibodies are more likely to be associated with specific symptoms. Muscle disease occurs more often with anti-Jo1 or anti-PL7. Interstitial lung disease occurs more often with anti-PL7, anti-PL12, anti-KS and anti-OJ autoantibodies. Some individuals with anti-OJ autoantibodies have developed severe muscle weakness.These autoantibodies are believed to be produced after a ‘triggering’ event such as a viral infection or exposure to certain drugs. When the immune system responds to these triggering events, something goes wrong, and these autoantibodies are created that could then damage healthy tissue.Some affected individuals may have a genetic predisposition to developing antisynthetase syndrome. A genetic predisposition means that a person may carry a gene or genes for a particular condition, but the condition will not develop unless other factors help to trigger the disease. Most likely, antisynthetase syndrome is a multifactorial disease, in which multiple factors including immune, genetic and environmental ones are necessary for the development of the disorder. | Causes of Antisynthetase Syndrome. The exact cause of antisynthetase syndrome is not fully understood. Affected individuals have autoantibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Autoantibodies are antibodies that mistakenly attack healthy tissue. In antisynthetase syndrome, affected individuals have autoantibodies that target certain enzymes in the body called aminoacyl-tRNA synthetases. Enzymes are specialized proteins that help to bring about specific biochemical reactions in the body and aminoacyl-tRNA synthetases help to regulate the production of other proteins and are important for the overall health and function of the body. Researches do not know why these autoantibodies target aminoacyl-tRNA synthetases. Not every person who develops these autoantibodies will go on to develop symptoms of antisynthetase syndrome.The exact role these autoantibodies play in the development of antisynthetase syndrome is not fully understood. The autoantibodies that have identified in this disorder include anti-Jo1, anti-EJ, anti-OJ, anti-PL7, anti-PL12, anti-SC, anti-KS, anti-JS, anti-HA, anti-YRS, anti-tryptophanyl and anti-Zo, and each of these target a different aminoacyl-tRNA synthetase. Anti-Jo1 is the most common autoantibody in individuals with antisynthetase syndrome.Some autoantibodies are more likely to be associated with specific symptoms. Muscle disease occurs more often with anti-Jo1 or anti-PL7. Interstitial lung disease occurs more often with anti-PL7, anti-PL12, anti-KS and anti-OJ autoantibodies. Some individuals with anti-OJ autoantibodies have developed severe muscle weakness.These autoantibodies are believed to be produced after a ‘triggering’ event such as a viral infection or exposure to certain drugs. When the immune system responds to these triggering events, something goes wrong, and these autoantibodies are created that could then damage healthy tissue.Some affected individuals may have a genetic predisposition to developing antisynthetase syndrome. A genetic predisposition means that a person may carry a gene or genes for a particular condition, but the condition will not develop unless other factors help to trigger the disease. Most likely, antisynthetase syndrome is a multifactorial disease, in which multiple factors including immune, genetic and environmental ones are necessary for the development of the disorder. | 88 | Antisynthetase Syndrome |
nord_88_3 | Affects of Antisynthetase Syndrome | Antisynthetase syndrome is a rare disorder that affects females twice as often as males. Age of onset can range from the late teens to the elderly, with a mean average of the 50s. The exact incidence or prevalence of the disorder is unknown. Because rare disorders often go undiagnosed or misdiagnosed, determining the true frequency of antisynthetase syndrome in the general population is difficult. | Affects of Antisynthetase Syndrome. Antisynthetase syndrome is a rare disorder that affects females twice as often as males. Age of onset can range from the late teens to the elderly, with a mean average of the 50s. The exact incidence or prevalence of the disorder is unknown. Because rare disorders often go undiagnosed or misdiagnosed, determining the true frequency of antisynthetase syndrome in the general population is difficult. | 88 | Antisynthetase Syndrome |
nord_88_4 | Related disorders of Antisynthetase Syndrome | Symptoms of the following disorders can be similar to those of antisynthetase syndrome. Comparisons may be useful for a differential diagnosis.Rheumatoid arthritis is a chronic, inflammatory disorder characterized by usually symmetric inflammation of the peripheral joints, which can eventually result in progressive destruction of the joints. The joints may be tender and warm to the touch. Pain and stiffness of the joints is common. Smaller joints are usually affected first. Generalized symptoms including fatigue and fever, and unintended weight loss can also occur. Rheumatoid arthritis occurs because the immune system malfunctions and mistakenly targets healthy tissue.Inflammatory myopathies are a group of disorders characterized by chronic inflammation of the muscles. Affected individuals may have muscle pain, muscle stiffness and muscle weakness. Additional symptoms can occur and how these disorders affect one person can vary greatly from how they affect another. Inflammatory myopathies include polymyositis, dermatomyositis, inclusion body myositis and necrotizing autoimmune myopathy. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Interstitial lung disease is a broad, general term for progressive inflammation and scarring of the lungs, particularly to the tissue and space around the air sacs or alveoli (interstitium). More than 200 different conditions are associated with interstitial lung disease. Individuals with antisynthetase syndrome that only show lung disease need to be differentiated from other causes of interstitial lung disease.The signs and symptoms of antisynthetase syndrome can also be seen in individuals with autoantibodies that target different proteins in the body. This includes anti-PM-Scl antibodies or anti-U1-ribonucleoprotein antibodies. These conditions are also seen in association with inflammatory muscle disorders (myopathies). Generally, individuals with antisynthetase syndrome have more pronounced muscle and lung disease. | Related disorders of Antisynthetase Syndrome. Symptoms of the following disorders can be similar to those of antisynthetase syndrome. Comparisons may be useful for a differential diagnosis.Rheumatoid arthritis is a chronic, inflammatory disorder characterized by usually symmetric inflammation of the peripheral joints, which can eventually result in progressive destruction of the joints. The joints may be tender and warm to the touch. Pain and stiffness of the joints is common. Smaller joints are usually affected first. Generalized symptoms including fatigue and fever, and unintended weight loss can also occur. Rheumatoid arthritis occurs because the immune system malfunctions and mistakenly targets healthy tissue.Inflammatory myopathies are a group of disorders characterized by chronic inflammation of the muscles. Affected individuals may have muscle pain, muscle stiffness and muscle weakness. Additional symptoms can occur and how these disorders affect one person can vary greatly from how they affect another. Inflammatory myopathies include polymyositis, dermatomyositis, inclusion body myositis and necrotizing autoimmune myopathy. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Interstitial lung disease is a broad, general term for progressive inflammation and scarring of the lungs, particularly to the tissue and space around the air sacs or alveoli (interstitium). More than 200 different conditions are associated with interstitial lung disease. Individuals with antisynthetase syndrome that only show lung disease need to be differentiated from other causes of interstitial lung disease.The signs and symptoms of antisynthetase syndrome can also be seen in individuals with autoantibodies that target different proteins in the body. This includes anti-PM-Scl antibodies or anti-U1-ribonucleoprotein antibodies. These conditions are also seen in association with inflammatory muscle disorders (myopathies). Generally, individuals with antisynthetase syndrome have more pronounced muscle and lung disease. | 88 | Antisynthetase Syndrome |
nord_88_5 | Diagnosis of Antisynthetase Syndrome | A diagnosis of antisynthetase syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and tests that confirm the presence of autoantibodies against the one of the aminoacyl-tRNA synthetase enzymes.Clinical Testing and Workup
Blood tests can reveal the presence of autoantibodies against one of the aminoacyl-tRNA synthetase enzymes. Every person who has one of these autoantibodies does not, necessarily, develop antisynthetase syndrome. There are published criteria that have been proposed to help with diagnosis. However, these criteria are not universally accepted, and some physicians think some people may have antisynthetase syndrome even if they do not meet the requirements for diagnosis under these guidelines. Based on some of the guidelines, affected individuals must also have two major criteria or one major criterion, or two minor criteria of the disorder. The two major criteria are interstitial lung disease and muscle disease. Minor criteria are arthritis, Raynaud phenomenon or thickening and cracking of the skin of the hands (mechanic’s hands).Blood tests can also reveal elevated levels of creatine kinase or aldolase, which are muscle enzymes. When these muscle enzymes are elevated, it is a sign of muscle damage. This is not specific to antisynthetase syndrome, and is a sign of many different types of muscle disease.A specialized imaging technique called high resolution computerized tomography (CT) scanning may be used to detect and evaluate lung disease. During CT scanning, a computer and x-rays are used to create cross-sectional images of certain tissue structures. High resolution CT scanning involves specific techniques that enhance or improve the resolution of the images. Pulmonary function tests may be administered to determine how well or poorly the lungs are working.Specialized testing that records electrical activity in skeletal muscle at rest and during muscle contraction (electromyography [EMG]) may be performed to determine the health of the muscles. | Diagnosis of Antisynthetase Syndrome. A diagnosis of antisynthetase syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and tests that confirm the presence of autoantibodies against the one of the aminoacyl-tRNA synthetase enzymes.Clinical Testing and Workup
Blood tests can reveal the presence of autoantibodies against one of the aminoacyl-tRNA synthetase enzymes. Every person who has one of these autoantibodies does not, necessarily, develop antisynthetase syndrome. There are published criteria that have been proposed to help with diagnosis. However, these criteria are not universally accepted, and some physicians think some people may have antisynthetase syndrome even if they do not meet the requirements for diagnosis under these guidelines. Based on some of the guidelines, affected individuals must also have two major criteria or one major criterion, or two minor criteria of the disorder. The two major criteria are interstitial lung disease and muscle disease. Minor criteria are arthritis, Raynaud phenomenon or thickening and cracking of the skin of the hands (mechanic’s hands).Blood tests can also reveal elevated levels of creatine kinase or aldolase, which are muscle enzymes. When these muscle enzymes are elevated, it is a sign of muscle damage. This is not specific to antisynthetase syndrome, and is a sign of many different types of muscle disease.A specialized imaging technique called high resolution computerized tomography (CT) scanning may be used to detect and evaluate lung disease. During CT scanning, a computer and x-rays are used to create cross-sectional images of certain tissue structures. High resolution CT scanning involves specific techniques that enhance or improve the resolution of the images. Pulmonary function tests may be administered to determine how well or poorly the lungs are working.Specialized testing that records electrical activity in skeletal muscle at rest and during muscle contraction (electromyography [EMG]) may be performed to determine the health of the muscles. | 88 | Antisynthetase Syndrome |
nord_88_6 | Therapies of Antisynthetase Syndrome | Treatment
The treatment of antisynthetase syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. General internists, specialists in the diagnosis and treatment of lung diseases (pulmonologists), specialists in the diagnosis and treatment of skeletal and muscle diseases (rheumatologists, neurologists, or orthopedists), specialists in the diagnosis and treatment of immunological diseases (immunologists) and other healthcare professionals may need to plan an affected person’s treatment systematically and comprehensively. Psychosocial support for the entire family is essential as well.There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with antisynthetase syndrome.Affected individuals may be treated with drugs that help to reduce inflammation called corticosteroids or drugs that suppress the activity of the immune system (immunosuppressive drugs). The effectiveness of these treatments and the amount of time an individual must remain on these medications will vary.A drug called hydroxychloroquine has been used to treat skin symptoms.Physical therapy is recommended to help to treat muscle disease by increasing muscle strength and reducing muscle wasting. | Therapies of Antisynthetase Syndrome. Treatment
The treatment of antisynthetase syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. General internists, specialists in the diagnosis and treatment of lung diseases (pulmonologists), specialists in the diagnosis and treatment of skeletal and muscle diseases (rheumatologists, neurologists, or orthopedists), specialists in the diagnosis and treatment of immunological diseases (immunologists) and other healthcare professionals may need to plan an affected person’s treatment systematically and comprehensively. Psychosocial support for the entire family is essential as well.There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with antisynthetase syndrome.Affected individuals may be treated with drugs that help to reduce inflammation called corticosteroids or drugs that suppress the activity of the immune system (immunosuppressive drugs). The effectiveness of these treatments and the amount of time an individual must remain on these medications will vary.A drug called hydroxychloroquine has been used to treat skin symptoms.Physical therapy is recommended to help to treat muscle disease by increasing muscle strength and reducing muscle wasting. | 88 | Antisynthetase Syndrome |
nord_89_0 | Overview of Antithrombin Deficiency | Antithrombin deficiency is a blood disorder characterized by the tendency to form clots in the veins (thrombosis). An inherited tendency to thrombosis is known as thrombophilia. Antithrombin is a substance in the blood that limits the blood's ability to clot (coagulation) and the primary inhibitor of thrombin, which is required for the development of blood clots; it also is the primary inhibitor of two clotting factors, factor Xa and factor IXa, that are required for the generation of thrombin. In people with congenital antithrombin deficiency, there is a reduced amount of this substance in the blood due to a genetic abnormality. Antithrombin deficiency may also be acquired; in such cases, the disorder may be reversible with resoluton/improvement in the disease process responsible for the deficiency. | Overview of Antithrombin Deficiency. Antithrombin deficiency is a blood disorder characterized by the tendency to form clots in the veins (thrombosis). An inherited tendency to thrombosis is known as thrombophilia. Antithrombin is a substance in the blood that limits the blood's ability to clot (coagulation) and the primary inhibitor of thrombin, which is required for the development of blood clots; it also is the primary inhibitor of two clotting factors, factor Xa and factor IXa, that are required for the generation of thrombin. In people with congenital antithrombin deficiency, there is a reduced amount of this substance in the blood due to a genetic abnormality. Antithrombin deficiency may also be acquired; in such cases, the disorder may be reversible with resoluton/improvement in the disease process responsible for the deficiency. | 89 | Antithrombin Deficiency |
nord_89_1 | Symptoms of Antithrombin Deficiency | People with antithrombin deficiency are at risk of developing a blood clot (thrombus) within a vein (thrombosis). The first episode of thrombosis typically occurs before the age of 40 years. A thrombus is a clump of blood cells (i.e., platelets, clotting factors, fibrin, etc.) that may become attached (adhere) to the interior wall of a blood vessel, usually a deep vein in the leg. This may be brought on by surgery, pregnancy, childbirth, trauma, or use of oral contraceptives. About 40 percent of people with antithrombin deficiency develop a thrombus that pulls away from the wall of a vein in the legs or pelvis (deep vein thrombosis or DVT) and travels through the blood stream to the lungs (pulmonary embolism or PE). Pulmonary emboli are dangerous and hence DVT and PE must be treated quickly. Thrombi also occur the superficial veins in the legs (superficial thrombophlebitis). Thrombi may also occur in the veins in the abdomen (mesenteric, portal, hepatic or splenic veins) or around the brain (sinus veins). Clots in the arteries of the heart may lead to heart attack (myocardial infarction) and clots in the arteries of the brain to stroke. However, arterial clots are rare in antithrombin deficiency.The most common symptoms of a DVT are swelling, pain, redness, and warmth of the affected leg; pulmonary emboli typically present as chest discomfort on breathing (so-called pleuritic chest pain, shortness of breath, and anxiety; in more severe cases, patients can become dizzy, pass out (syncope), or go into shock. There are several reports in the medical literature of newborn children with antithrombin deficiency who develop blood clots. This occurs rarely however, and may be due to the protective effect of higher levels of a secondary plasma inhibitor of thrombin called alpha-2 macroglobulin. | Symptoms of Antithrombin Deficiency. People with antithrombin deficiency are at risk of developing a blood clot (thrombus) within a vein (thrombosis). The first episode of thrombosis typically occurs before the age of 40 years. A thrombus is a clump of blood cells (i.e., platelets, clotting factors, fibrin, etc.) that may become attached (adhere) to the interior wall of a blood vessel, usually a deep vein in the leg. This may be brought on by surgery, pregnancy, childbirth, trauma, or use of oral contraceptives. About 40 percent of people with antithrombin deficiency develop a thrombus that pulls away from the wall of a vein in the legs or pelvis (deep vein thrombosis or DVT) and travels through the blood stream to the lungs (pulmonary embolism or PE). Pulmonary emboli are dangerous and hence DVT and PE must be treated quickly. Thrombi also occur the superficial veins in the legs (superficial thrombophlebitis). Thrombi may also occur in the veins in the abdomen (mesenteric, portal, hepatic or splenic veins) or around the brain (sinus veins). Clots in the arteries of the heart may lead to heart attack (myocardial infarction) and clots in the arteries of the brain to stroke. However, arterial clots are rare in antithrombin deficiency.The most common symptoms of a DVT are swelling, pain, redness, and warmth of the affected leg; pulmonary emboli typically present as chest discomfort on breathing (so-called pleuritic chest pain, shortness of breath, and anxiety; in more severe cases, patients can become dizzy, pass out (syncope), or go into shock. There are several reports in the medical literature of newborn children with antithrombin deficiency who develop blood clots. This occurs rarely however, and may be due to the protective effect of higher levels of a secondary plasma inhibitor of thrombin called alpha-2 macroglobulin. | 89 | Antithrombin Deficiency |
nord_89_2 | Causes of Antithrombin Deficiency | Antithrombin deficiency may be inherited or acquired. Inherited AT deficiency increases the risk of blood clots; acquired AT deficiency often does not. Acquired AT deficiency is the consequence of some other disorder, usually involving the liver, kidneys, or treatment of certain types of blood disorders, e.g., leukemias with a drug called L-asparaginase. Low antithrombin levels may also be temporarily associated with some other conditions such as heparin therapy, disseminated intravascular coagulation usually due to a severe infection of the blood stream, severe trauma, severe burns or the presence of acute blood clots.Hereditary antithrombin deficiency is caused by changes (mutations) in the SERPINC1 gene and many different mutations in this gene are responsible for individual cases of antithrombin deficiency.Hereditary antithrombin deficiency is inherited as an autosomal dominant condition. Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. Heterozygote is the term used to describe such a person. However, not every person who has the altered gene will develop a blood clot. Geneticists call this variable clinical penetrance. Thus, antithrombin deficiency is an autosomal dominant disorder with variable clinical penetrance. The altered gene can be inherited from either parent, or very rarely can be the result of a new mutation in the affected individual. The risk of passing the altered gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.A person who inherits two altered genes, one from each of the parents is known as a homozygote. Homozygous babies with antithrombin deficiency seldom survive though there are rare cases with so-called type IIB mutations. | Causes of Antithrombin Deficiency. Antithrombin deficiency may be inherited or acquired. Inherited AT deficiency increases the risk of blood clots; acquired AT deficiency often does not. Acquired AT deficiency is the consequence of some other disorder, usually involving the liver, kidneys, or treatment of certain types of blood disorders, e.g., leukemias with a drug called L-asparaginase. Low antithrombin levels may also be temporarily associated with some other conditions such as heparin therapy, disseminated intravascular coagulation usually due to a severe infection of the blood stream, severe trauma, severe burns or the presence of acute blood clots.Hereditary antithrombin deficiency is caused by changes (mutations) in the SERPINC1 gene and many different mutations in this gene are responsible for individual cases of antithrombin deficiency.Hereditary antithrombin deficiency is inherited as an autosomal dominant condition. Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. Heterozygote is the term used to describe such a person. However, not every person who has the altered gene will develop a blood clot. Geneticists call this variable clinical penetrance. Thus, antithrombin deficiency is an autosomal dominant disorder with variable clinical penetrance. The altered gene can be inherited from either parent, or very rarely can be the result of a new mutation in the affected individual. The risk of passing the altered gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.A person who inherits two altered genes, one from each of the parents is known as a homozygote. Homozygous babies with antithrombin deficiency seldom survive though there are rare cases with so-called type IIB mutations. | 89 | Antithrombin Deficiency |
nord_89_3 | Affects of Antithrombin Deficiency | Antithrombin deficiency is a rare disorder that affects males and females in equal numbers. Type I antithrombin deficiency is the most common subtype and is thought to occur in about one in every 3,000 to 5,000 people in the United States and is not limited to any particular ethnic group. It is estimated that approximately 1 percent of people who have venous thrombosis and embolism have congenital antithrombin deficiency. The acquired form of antithrombin deficiency is more prevalent than the congenital form of the disorder. | Affects of Antithrombin Deficiency. Antithrombin deficiency is a rare disorder that affects males and females in equal numbers. Type I antithrombin deficiency is the most common subtype and is thought to occur in about one in every 3,000 to 5,000 people in the United States and is not limited to any particular ethnic group. It is estimated that approximately 1 percent of people who have venous thrombosis and embolism have congenital antithrombin deficiency. The acquired form of antithrombin deficiency is more prevalent than the congenital form of the disorder. | 89 | Antithrombin Deficiency |
nord_89_4 | Related disorders of Antithrombin Deficiency | Symptoms of the following disorders can be similar to those of antithrombin deficiency. Comparisons may be useful for a differential diagnosis:Antiphospholipid syndrome (APLS) is an autoimmune disorder characterized by blood clots in the veins or arteries. Clots in arteries may break away from the walls of the blood vessels and result in stroke. Women with this disorder can experience a high rate of miscarriages. Other symptoms may include inflammation and thickening of the valves of the heart, migraine headaches, and skin rashes. (For more information on this disorder, choose “Antiphospholipid” as your search term in the Rare Disease Database.)Protein C deficiency is an inherited disorder characterized by the abnormal formation of blood clots and pulmonary emboli. Protein C is a vitamin K-dependent coagulation factor. People with this deficiency have approximately 50 percent of the normal level of this factor in their blood. Symptoms may include blood clots in the deep veins of the legs, pulmonary emboli, and/or the venous sinuses of the brain. (For more information on this disorder, choose “Protein C” as your search term in the Rare Disease Database.)Protein S deficiency is another inherited disorder characterized by the formation of recurrent blood clots and emboli. Protein S is also a vitamin K-dependent coagulation factor.The Factor V Leiden and prothrombin G20210A mutations are the most common genetic variants leading to an increased risk of venous thrombosis. The frequency of the Factor V Leiden and prothrombin mutations in the general Caucasian population in the US is approximately 6% and 2%, respectively. | Related disorders of Antithrombin Deficiency. Symptoms of the following disorders can be similar to those of antithrombin deficiency. Comparisons may be useful for a differential diagnosis:Antiphospholipid syndrome (APLS) is an autoimmune disorder characterized by blood clots in the veins or arteries. Clots in arteries may break away from the walls of the blood vessels and result in stroke. Women with this disorder can experience a high rate of miscarriages. Other symptoms may include inflammation and thickening of the valves of the heart, migraine headaches, and skin rashes. (For more information on this disorder, choose “Antiphospholipid” as your search term in the Rare Disease Database.)Protein C deficiency is an inherited disorder characterized by the abnormal formation of blood clots and pulmonary emboli. Protein C is a vitamin K-dependent coagulation factor. People with this deficiency have approximately 50 percent of the normal level of this factor in their blood. Symptoms may include blood clots in the deep veins of the legs, pulmonary emboli, and/or the venous sinuses of the brain. (For more information on this disorder, choose “Protein C” as your search term in the Rare Disease Database.)Protein S deficiency is another inherited disorder characterized by the formation of recurrent blood clots and emboli. Protein S is also a vitamin K-dependent coagulation factor.The Factor V Leiden and prothrombin G20210A mutations are the most common genetic variants leading to an increased risk of venous thrombosis. The frequency of the Factor V Leiden and prothrombin mutations in the general Caucasian population in the US is approximately 6% and 2%, respectively. | 89 | Antithrombin Deficiency |
nord_89_5 | Diagnosis of Antithrombin Deficiency | A low blood level of antithrombin suggests that the patient may have antithrombin deficiency. However, it is important to keep in mind that many conditions can lower antithrombin levels (acute clots, heparin therapy, liver or kidney disease, etc.) without the patient having inherited antithrombin deficiency. Repeat testing should be done at a time when the patient is not ill, is not on heparin and does not have related medical problems. | Diagnosis of Antithrombin Deficiency. A low blood level of antithrombin suggests that the patient may have antithrombin deficiency. However, it is important to keep in mind that many conditions can lower antithrombin levels (acute clots, heparin therapy, liver or kidney disease, etc.) without the patient having inherited antithrombin deficiency. Repeat testing should be done at a time when the patient is not ill, is not on heparin and does not have related medical problems. | 89 | Antithrombin Deficiency |
nord_89_6 | Therapies of Antithrombin Deficiency | TreatmentDue to a lack of clinical studies, hematologists differ in their opinions regarding the treatment of antithrombin deficiency. Often, intravenous antithrombin concentrates are prescribed when surgery or infant delivery is close at hand. Antithrombin concentrates are also used to prevent venous clots when blood thinners (such as heparin) are not advisable because they may lead to an increased risk of bleeding. This is especially true for neuro-surgery and in severe trauma or at the time of delivery.For people with very low antithrombin levels, heparin may not work well if administered alone. This is called heparin resistance. In order for heparin to work properly an adequate amount of antithrombin must be present in the blood. If heparin treatment is ineffective, then antithrombin concentrate may be prescribed.Women with antithrombin deficiency are at particularly high risk for developing clots during pregnancy or after delivery. Reports of the incidence of blot clots during pregnancy in women with antithrombin deficiency range from 3% to 50%. Many recommend the use of subcutaneous low molecular weight heparin injections during pregnancy for women with antithrombin deficiency.Pregnant women with antithrombin deficiency are at slightly increased risk of losing the fetus without treatment. Pregnancy loss is likely due to blood clots forming in the placenta and cutting off the blood supply and oxygen to the fetus.As noted above, patients with antithrombin deficiency who undergo surgery are at increased risk of a thromboembolic event unless appropriate preventive measures are taken. The duration of treatment with blood thinners or antithrombin concentrate depends on the type of surgery. In some cases, treatment will last only a few days while in other instances treatment may last for several weeks.A family in which one or more members have antithrombin deficiency should consult with a hematologist and genetic counselor, who can help the family understand and cope with the disorder.Two different concentrates of antithrombin concentrate are available in the US. Antithrombin concentrate (Thrombate) is a highly purified and viral-safe product prepared from pooled normal human plasma. Its half-life in the circulation is approximately 2.8 to 4.8 days. A recombinant human antithrombin (Atryn), produced from the milk of transgenic goats, is also available. This product is only approved for use in high-risk situations (eg, surgery, childbirth) in patients with antithrombin deficiency. | Therapies of Antithrombin Deficiency. TreatmentDue to a lack of clinical studies, hematologists differ in their opinions regarding the treatment of antithrombin deficiency. Often, intravenous antithrombin concentrates are prescribed when surgery or infant delivery is close at hand. Antithrombin concentrates are also used to prevent venous clots when blood thinners (such as heparin) are not advisable because they may lead to an increased risk of bleeding. This is especially true for neuro-surgery and in severe trauma or at the time of delivery.For people with very low antithrombin levels, heparin may not work well if administered alone. This is called heparin resistance. In order for heparin to work properly an adequate amount of antithrombin must be present in the blood. If heparin treatment is ineffective, then antithrombin concentrate may be prescribed.Women with antithrombin deficiency are at particularly high risk for developing clots during pregnancy or after delivery. Reports of the incidence of blot clots during pregnancy in women with antithrombin deficiency range from 3% to 50%. Many recommend the use of subcutaneous low molecular weight heparin injections during pregnancy for women with antithrombin deficiency.Pregnant women with antithrombin deficiency are at slightly increased risk of losing the fetus without treatment. Pregnancy loss is likely due to blood clots forming in the placenta and cutting off the blood supply and oxygen to the fetus.As noted above, patients with antithrombin deficiency who undergo surgery are at increased risk of a thromboembolic event unless appropriate preventive measures are taken. The duration of treatment with blood thinners or antithrombin concentrate depends on the type of surgery. In some cases, treatment will last only a few days while in other instances treatment may last for several weeks.A family in which one or more members have antithrombin deficiency should consult with a hematologist and genetic counselor, who can help the family understand and cope with the disorder.Two different concentrates of antithrombin concentrate are available in the US. Antithrombin concentrate (Thrombate) is a highly purified and viral-safe product prepared from pooled normal human plasma. Its half-life in the circulation is approximately 2.8 to 4.8 days. A recombinant human antithrombin (Atryn), produced from the milk of transgenic goats, is also available. This product is only approved for use in high-risk situations (eg, surgery, childbirth) in patients with antithrombin deficiency. | 89 | Antithrombin Deficiency |
nord_90_0 | Overview of Antley-Bixler Syndrome | Antley-Bixler syndrome is a rare genetic disorder that can cause structural changes of the skull, bones of the face and other skeletal abnormalities. The disorder is typically associated with premature closure of joints (cranial sutures) between particular bones of the skull (craniosynostosis). Many affected infants and children also may have a prominent forehead, underdeveloped midfacial regions (midfacial hypoplasia), protruding eyes (proptosis), and low-set ears.Additional skeletal abnormalities are usually present, such as fusion of certain bones of the arms (e.g., radiohumeral or radioulnar synostosis), long, thin fingers and toes (arachnodactyly), and bowing of the thigh bones. In addition, certain joints in the arms and legs may become permanently flexed or extended in fixed postures (joint contractures), resulting in restricted movements.Antley-Bixler syndrome can be caused by changes (mutations) in the POR gene and the FGFR2 gene. | Overview of Antley-Bixler Syndrome. Antley-Bixler syndrome is a rare genetic disorder that can cause structural changes of the skull, bones of the face and other skeletal abnormalities. The disorder is typically associated with premature closure of joints (cranial sutures) between particular bones of the skull (craniosynostosis). Many affected infants and children also may have a prominent forehead, underdeveloped midfacial regions (midfacial hypoplasia), protruding eyes (proptosis), and low-set ears.Additional skeletal abnormalities are usually present, such as fusion of certain bones of the arms (e.g., radiohumeral or radioulnar synostosis), long, thin fingers and toes (arachnodactyly), and bowing of the thigh bones. In addition, certain joints in the arms and legs may become permanently flexed or extended in fixed postures (joint contractures), resulting in restricted movements.Antley-Bixler syndrome can be caused by changes (mutations) in the POR gene and the FGFR2 gene. | 90 | Antley-Bixler Syndrome |
nord_90_1 | Symptoms of Antley-Bixler Syndrome | Antley-Bixler syndrome is typically characterized by structural changes of the skull, bones of the face and other skeletal abnormalities. In most affected infants, there is premature closure of the joints (sutures) between different portions of the skull (craniosynostosis) Additional craniofacial abnormalities may include a large, prominent forehead (frontal bossing), underdeveloped middle regions of the face (midfacial hypoplasia); a large nose with a low nasal bridge; protruding eyes (proptosis); and low-set, malformed (dysplastic) ears.Antley-Bixler syndrome is also characterized by other distinctive skeletal changes. These may include fusion of bones of the arms that are next to each other (adjacent), particularly the forearm bone on the thumb side of the arm (radius) and the long bone of the upper arm (radiohumeral synostosis). In addition, there can be permanent flexion or extension of certain joints in a fixed position (joint contractures), leading to limited movements of the fingers, wrists, ankles, knees, and/or hips. Affected individuals may also have unusually long, thin fingers and toes (camptodactyly), structural changes on the bottom of the feet (“rocker-bottom” feet); or bowing and/or fractures of the thigh bones.In some affected infants, a bony or thin layer of tissue may block the passageway between the nose and throat (choanal stenosis or atresia), leading to difficulty breathing. If this symptom is not treated promptly early in life, it may cause life-threatening respiratory problems. Some individuals with Antley-Bixler syndrome may have additional symptoms. These may include certain structural defects of the urinary and genital organs (urogenital defects), inability to produce cholesterol from steroids (impaired steroidogenesis), developmental delay, and intellectual disability. ABS1 is the name given to the subtype that includes genital anomalies and disordered steroidogenesis. ABS1 is also a severe form of cytochrome P450 oxidoreductase deficiency. ABS2 is the name given to the subtype that does not include genital anomalies and disordered steroidogenesis. | Symptoms of Antley-Bixler Syndrome. Antley-Bixler syndrome is typically characterized by structural changes of the skull, bones of the face and other skeletal abnormalities. In most affected infants, there is premature closure of the joints (sutures) between different portions of the skull (craniosynostosis) Additional craniofacial abnormalities may include a large, prominent forehead (frontal bossing), underdeveloped middle regions of the face (midfacial hypoplasia); a large nose with a low nasal bridge; protruding eyes (proptosis); and low-set, malformed (dysplastic) ears.Antley-Bixler syndrome is also characterized by other distinctive skeletal changes. These may include fusion of bones of the arms that are next to each other (adjacent), particularly the forearm bone on the thumb side of the arm (radius) and the long bone of the upper arm (radiohumeral synostosis). In addition, there can be permanent flexion or extension of certain joints in a fixed position (joint contractures), leading to limited movements of the fingers, wrists, ankles, knees, and/or hips. Affected individuals may also have unusually long, thin fingers and toes (camptodactyly), structural changes on the bottom of the feet (“rocker-bottom” feet); or bowing and/or fractures of the thigh bones.In some affected infants, a bony or thin layer of tissue may block the passageway between the nose and throat (choanal stenosis or atresia), leading to difficulty breathing. If this symptom is not treated promptly early in life, it may cause life-threatening respiratory problems. Some individuals with Antley-Bixler syndrome may have additional symptoms. These may include certain structural defects of the urinary and genital organs (urogenital defects), inability to produce cholesterol from steroids (impaired steroidogenesis), developmental delay, and intellectual disability. ABS1 is the name given to the subtype that includes genital anomalies and disordered steroidogenesis. ABS1 is also a severe form of cytochrome P450 oxidoreductase deficiency. ABS2 is the name given to the subtype that does not include genital anomalies and disordered steroidogenesis. | 90 | Antley-Bixler Syndrome |
nord_90_2 | Causes of Antley-Bixler Syndrome | Antley-Bixler syndrome can be caused by mutations in two different genes. ABS1 is associated with mutations in the POR gene and is inherited in an autosomal recessive pattern. This means that a person will have ABS1 when he or she inherits two non-working copies of the POR gene, one from each parent. If an individual receives one working copy of the gene and one not working copy of the gene, the person will be a carrier for the syndrome but will not show symptoms. When both parents are carriers for the syndrome, there is a 25 percent chance the child will have ABS1. Additionally, there is fifty percent chance their child will be carriers of the condition (just like their parents) and a twenty-five percent chance that their child will receive both working copies of the gene. The risk is the same for each pregnancy. ABS2 is associated with mutations in the FGFR2 gene. In this subtype, the condition is thought to be caused by spontaneous (new) changes of the gene. The condition then may be transmitted in an autosomal dominant pattern in subsequent generations. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.It is important to note that there are a number of syndromes that have been identified which are associated with mutations of the FGFR2 gene including Apert, Crouzon, and Pfeiffer syndromes. (For further information on these disorders, please see the “Related Disorders” section of this report below.)There have been a few reported cases which show that symptoms similar to Antley-Bixler syndrome may have resulted from maternal use of the antifungal medication (fluconazole) during early pregnancy. There is not a lot of research showing why this medication causes symptoms similar to Antley-Bixler syndrome. | Causes of Antley-Bixler Syndrome. Antley-Bixler syndrome can be caused by mutations in two different genes. ABS1 is associated with mutations in the POR gene and is inherited in an autosomal recessive pattern. This means that a person will have ABS1 when he or she inherits two non-working copies of the POR gene, one from each parent. If an individual receives one working copy of the gene and one not working copy of the gene, the person will be a carrier for the syndrome but will not show symptoms. When both parents are carriers for the syndrome, there is a 25 percent chance the child will have ABS1. Additionally, there is fifty percent chance their child will be carriers of the condition (just like their parents) and a twenty-five percent chance that their child will receive both working copies of the gene. The risk is the same for each pregnancy. ABS2 is associated with mutations in the FGFR2 gene. In this subtype, the condition is thought to be caused by spontaneous (new) changes of the gene. The condition then may be transmitted in an autosomal dominant pattern in subsequent generations. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.It is important to note that there are a number of syndromes that have been identified which are associated with mutations of the FGFR2 gene including Apert, Crouzon, and Pfeiffer syndromes. (For further information on these disorders, please see the “Related Disorders” section of this report below.)There have been a few reported cases which show that symptoms similar to Antley-Bixler syndrome may have resulted from maternal use of the antifungal medication (fluconazole) during early pregnancy. There is not a lot of research showing why this medication causes symptoms similar to Antley-Bixler syndrome. | 90 | Antley-Bixler Syndrome |
nord_90_3 | Affects of Antley-Bixler Syndrome | This condition has been described in over 30 patients to date. The estimated prevalence for the condition is less than 1 in 1,000,000. | Affects of Antley-Bixler Syndrome. This condition has been described in over 30 patients to date. The estimated prevalence for the condition is less than 1 in 1,000,000. | 90 | Antley-Bixler Syndrome |
nord_90_4 | Related disorders of Antley-Bixler Syndrome | Symptoms of the following disorders can be similar to those of Antley-Bixler syndrome. Comparisons may be useful for a differential diagnosis:Primary craniosynostosis is a rare disorder of the skull. It occurs when there is an early closure of the bones (sutures) in the skull resulting in an abnormally shaped head. The severity of the symptoms and shape of the skull depend on which skull bones close early. In this condition, the head may be larger than normal due to accumulation of fluid (hydrocephaly) in the skull. (For more information on this disorder, choose “primary craniosynostosis” as your search term in the Rare Disease Database.)Camptomelic syndrome is a rare congenital skeletal disorder inherited in an autosomal recessive pattern. It is characterized by short stature and structural defects in the long bones of the legs. The bones of the shoulder and the pelvis can also have structural defects. Eleven pairs of ribs instead of the usual twelve may also be present. Respiratory distress due to the underdevelopment of the rib cage is the most serious complication of this condition. (For more information on this disorder, choose “camptomelic” as your search term in the Rare Disease Database.)Acrocephalosyndactyly syndromes are rare disorders that are characterized by a pointed head caused by the early closure of the bones in the skull. Other physical characteristics may include webbed fingers and other structural changes in the skeleton. Some characteristics of these syndromes are similar to those in Antley-Bixler syndrome.Apert syndrome is a rare inherited disorder characterized by intellectual disability along with malformations of the head, fingers, and toes. Apert syndrome is also known as acrocephalosyndactyly type I. The head has a long narrow appearance with a pointed top (acrocephaly or oxycephaly) and some fingers may be webbed (syndactyly). Other features may include widely spaced eyes (hypertelorism), a bulging appearance to the eyeballs (exophthalmos), and/or a high pointed palate. (For more information on this disorder, choose “Apert” as your search term in the Rare Disease Database.)Crouzon disease is a rare inherited disorder characterized by the premature closure of the bones of the skull (craniosynostosis) accompanied by unusual facial features, developmental delay, intellectual disability, and disturbances in vision and hearing. This disorder is also known as acrocephalosyndactyly type II. Other features of this disorder may include widely spaced eyes (hypertelorism), a bulging appearance to the eyeballs (exophthalmos), crossed eyes (strabismus), a beaked nose with a deviated septum, and/or underdevelopment of the jaw (hypoplastic maxilla). Spinal anomalies may also be present. (For more information on this disorder, choose “Crouzon” as your search term in the Rare Disease Database.)Saethre-Chotzen syndrome is a rare congenital disorder thought to be inherited in an autosomal dominant pattern. This disorder is characterized by various craniofacial and skeletal abnormalities. It is also known as acrocephalosyndactyly type III. Features include a small head (microcephaly), premature closure of the bones of the skull (craniosynostosis), mildly fused webbed fingers and/or toes (syndactyly), droopy eyelids, widely spaced eyes, mild to moderate intellectual disability, and facial abnormalities. (For more information on this disorder, choose “Saethre-Chotzen” as your search term in the Rare Disease Database.)Pfeiffer syndrome is a rare disorder inherited in an autosomal dominant pattern that primarily affects the bones. This disorder is also known as acrocephalosyndactyly type V. Infants with Pfeiffer syndrome usually have a short, pointed head (acrobrachycephaly) and other deformities of the face, jaws, and teeth. Webbed fingers or toes (syndactyly) and other abnormalities of the thumbs or big toes may also occur. Symptoms can vary from mild to severe. (For more information on this disorder, choose “Pfeiffer” as your search term in the Rare Disease Database.)Carpenter syndrome is a rare inherited disorder characterized by abnormalities of the head, hands, and genitals. Intellectual disability is also present in children with this disorder. This disorder is also known as acrocephalopolysyndactyly type II. Carpenter syndrome is a form of craniosynostosis, marked by the premature closure of the bones of the skull resulting in an abnormally shaped head. Other features may include down- slanting eyes, a flattened nose, low-set eyes, and an usually small jaw. Obesity and heart anomalies may also occur. (For more information on this disorder, choose “Carpenter” as your search term in the Rare Disease Database.)Sakati syndrome (also known as acrocephalopolysyndactyly type III) is a rare inherited disorder characterized by an abnormally shaped head and abnormalities of the fingers. Other features include unusually short legs, bowing of the bone that extends from the hips to the knees (femur), underdevelopment of the ears, lack of scalp hair (alopecia), unusually dry skin, failure of the testicles to descend into the scrotum (cryptorchidism), an abnormally small penis (microphallus), and/or congenital heart disease. Goodman syndrome is a rare inherited disorder of infancy characterized by abnormalities of the head, hands, and genitals. This disorder is also known as acrocephalopolysydactyly type IV and is a mild form of Carpenter syndrome. The head is typically abnormally shaped and the eyes may be low-set. Intellectual disability does not occur and hand deformities are less pronounced than in Carpenter syndrome.B3GAT3-related disorder is a rare inherited disorder of infancy characterized by many of the same symptoms and signs as Antley-Bixler syndrome. However, this condition is associated with multiple neonatal fractures and cardiovascular abnormalities which are less common in ABS. | Related disorders of Antley-Bixler Syndrome. Symptoms of the following disorders can be similar to those of Antley-Bixler syndrome. Comparisons may be useful for a differential diagnosis:Primary craniosynostosis is a rare disorder of the skull. It occurs when there is an early closure of the bones (sutures) in the skull resulting in an abnormally shaped head. The severity of the symptoms and shape of the skull depend on which skull bones close early. In this condition, the head may be larger than normal due to accumulation of fluid (hydrocephaly) in the skull. (For more information on this disorder, choose “primary craniosynostosis” as your search term in the Rare Disease Database.)Camptomelic syndrome is a rare congenital skeletal disorder inherited in an autosomal recessive pattern. It is characterized by short stature and structural defects in the long bones of the legs. The bones of the shoulder and the pelvis can also have structural defects. Eleven pairs of ribs instead of the usual twelve may also be present. Respiratory distress due to the underdevelopment of the rib cage is the most serious complication of this condition. (For more information on this disorder, choose “camptomelic” as your search term in the Rare Disease Database.)Acrocephalosyndactyly syndromes are rare disorders that are characterized by a pointed head caused by the early closure of the bones in the skull. Other physical characteristics may include webbed fingers and other structural changes in the skeleton. Some characteristics of these syndromes are similar to those in Antley-Bixler syndrome.Apert syndrome is a rare inherited disorder characterized by intellectual disability along with malformations of the head, fingers, and toes. Apert syndrome is also known as acrocephalosyndactyly type I. The head has a long narrow appearance with a pointed top (acrocephaly or oxycephaly) and some fingers may be webbed (syndactyly). Other features may include widely spaced eyes (hypertelorism), a bulging appearance to the eyeballs (exophthalmos), and/or a high pointed palate. (For more information on this disorder, choose “Apert” as your search term in the Rare Disease Database.)Crouzon disease is a rare inherited disorder characterized by the premature closure of the bones of the skull (craniosynostosis) accompanied by unusual facial features, developmental delay, intellectual disability, and disturbances in vision and hearing. This disorder is also known as acrocephalosyndactyly type II. Other features of this disorder may include widely spaced eyes (hypertelorism), a bulging appearance to the eyeballs (exophthalmos), crossed eyes (strabismus), a beaked nose with a deviated septum, and/or underdevelopment of the jaw (hypoplastic maxilla). Spinal anomalies may also be present. (For more information on this disorder, choose “Crouzon” as your search term in the Rare Disease Database.)Saethre-Chotzen syndrome is a rare congenital disorder thought to be inherited in an autosomal dominant pattern. This disorder is characterized by various craniofacial and skeletal abnormalities. It is also known as acrocephalosyndactyly type III. Features include a small head (microcephaly), premature closure of the bones of the skull (craniosynostosis), mildly fused webbed fingers and/or toes (syndactyly), droopy eyelids, widely spaced eyes, mild to moderate intellectual disability, and facial abnormalities. (For more information on this disorder, choose “Saethre-Chotzen” as your search term in the Rare Disease Database.)Pfeiffer syndrome is a rare disorder inherited in an autosomal dominant pattern that primarily affects the bones. This disorder is also known as acrocephalosyndactyly type V. Infants with Pfeiffer syndrome usually have a short, pointed head (acrobrachycephaly) and other deformities of the face, jaws, and teeth. Webbed fingers or toes (syndactyly) and other abnormalities of the thumbs or big toes may also occur. Symptoms can vary from mild to severe. (For more information on this disorder, choose “Pfeiffer” as your search term in the Rare Disease Database.)Carpenter syndrome is a rare inherited disorder characterized by abnormalities of the head, hands, and genitals. Intellectual disability is also present in children with this disorder. This disorder is also known as acrocephalopolysyndactyly type II. Carpenter syndrome is a form of craniosynostosis, marked by the premature closure of the bones of the skull resulting in an abnormally shaped head. Other features may include down- slanting eyes, a flattened nose, low-set eyes, and an usually small jaw. Obesity and heart anomalies may also occur. (For more information on this disorder, choose “Carpenter” as your search term in the Rare Disease Database.)Sakati syndrome (also known as acrocephalopolysyndactyly type III) is a rare inherited disorder characterized by an abnormally shaped head and abnormalities of the fingers. Other features include unusually short legs, bowing of the bone that extends from the hips to the knees (femur), underdevelopment of the ears, lack of scalp hair (alopecia), unusually dry skin, failure of the testicles to descend into the scrotum (cryptorchidism), an abnormally small penis (microphallus), and/or congenital heart disease. Goodman syndrome is a rare inherited disorder of infancy characterized by abnormalities of the head, hands, and genitals. This disorder is also known as acrocephalopolysydactyly type IV and is a mild form of Carpenter syndrome. The head is typically abnormally shaped and the eyes may be low-set. Intellectual disability does not occur and hand deformities are less pronounced than in Carpenter syndrome.B3GAT3-related disorder is a rare inherited disorder of infancy characterized by many of the same symptoms and signs as Antley-Bixler syndrome. However, this condition is associated with multiple neonatal fractures and cardiovascular abnormalities which are less common in ABS. | 90 | Antley-Bixler Syndrome |
nord_90_5 | Diagnosis of Antley-Bixler Syndrome | The diagnosis of Antley-Bixler syndrome is usually made after birth (postnatally) based upon a thorough clinical evaluation and characteristic physical findings. Other imaging procedures and genetic testing may also be conducted to diagnose the disorder. In some children, a diagnosis of Antley-Bixler syndrome may be suggested before birth (prenatally) based upon test such as ultrasound. Ultrasound allows us to generate an image of the developing fetus, which may then reveal characteristic findings that are associated with the disorder. If there is a known family history of the condition, targeted genetic testing is available for patient families. | Diagnosis of Antley-Bixler Syndrome. The diagnosis of Antley-Bixler syndrome is usually made after birth (postnatally) based upon a thorough clinical evaluation and characteristic physical findings. Other imaging procedures and genetic testing may also be conducted to diagnose the disorder. In some children, a diagnosis of Antley-Bixler syndrome may be suggested before birth (prenatally) based upon test such as ultrasound. Ultrasound allows us to generate an image of the developing fetus, which may then reveal characteristic findings that are associated with the disorder. If there is a known family history of the condition, targeted genetic testing is available for patient families. | 90 | Antley-Bixler Syndrome |
nord_90_6 | Therapies of Antley-Bixler Syndrome | TreatmentThe treatment of Antley-Bixler syndrome is directed toward the specific symptoms that are seen in each individual. Such treatment requires the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan the treatment for a child with this condition. These professionals may include pediatricians, surgeons, physicians who specialize in disorders of specific body areas and organs. In individuals with Antley-Bixler syndrome, treatment typically includes surgery. The surgical procedures performed will depend upon the severity of the skeletal problems and its associated symptoms. It is possible that multiple surgeries will be needed in order to treat the malformations present.There is no cure for the condition. All treatment is supportive and aimed at managing symptoms. However, early intervention may be important in ensuring that affected children reach their potential. For example, physical therapy is typically recommended to help improve the range of movement at certain joint contractures. Other therapies that may aide in managing symptoms include occupational therapy and speech therapy. Because this is a genetic condition, individuals with Antley-Bixler syndrome and their families would benefit from meeting with a genetic counselor. Genetic counselors are professionals who have specialized education in genetics and counseling to provide personalized help patients may need as they make decisions about their genetic health. | Therapies of Antley-Bixler Syndrome. TreatmentThe treatment of Antley-Bixler syndrome is directed toward the specific symptoms that are seen in each individual. Such treatment requires the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan the treatment for a child with this condition. These professionals may include pediatricians, surgeons, physicians who specialize in disorders of specific body areas and organs. In individuals with Antley-Bixler syndrome, treatment typically includes surgery. The surgical procedures performed will depend upon the severity of the skeletal problems and its associated symptoms. It is possible that multiple surgeries will be needed in order to treat the malformations present.There is no cure for the condition. All treatment is supportive and aimed at managing symptoms. However, early intervention may be important in ensuring that affected children reach their potential. For example, physical therapy is typically recommended to help improve the range of movement at certain joint contractures. Other therapies that may aide in managing symptoms include occupational therapy and speech therapy. Because this is a genetic condition, individuals with Antley-Bixler syndrome and their families would benefit from meeting with a genetic counselor. Genetic counselors are professionals who have specialized education in genetics and counseling to provide personalized help patients may need as they make decisions about their genetic health. | 90 | Antley-Bixler Syndrome |
nord_91_0 | Overview of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | SummaryAP-4-associated hereditary spastic paraplegia (AP-4-HSP) is a group of neurodevelopmental and slowly progressive neurological disorders that generally present with global developmental delay, moderate to severe intellectual disability, impaired/absent speech, small head size (microcephaly), seizures and progressive motor symptoms. Low muscle tone (hypotonia) in infancy develops into high muscle tone (hypertonia), resulting in spasticity of the legs that leads to the inability to walk (non-ambulation) and wheelchair reliance. Spasticity may progress to the upper extremities, leading to the partial or total loss of use of all four limbs and torso (tetraplegia). | Overview of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). SummaryAP-4-associated hereditary spastic paraplegia (AP-4-HSP) is a group of neurodevelopmental and slowly progressive neurological disorders that generally present with global developmental delay, moderate to severe intellectual disability, impaired/absent speech, small head size (microcephaly), seizures and progressive motor symptoms. Low muscle tone (hypotonia) in infancy develops into high muscle tone (hypertonia), resulting in spasticity of the legs that leads to the inability to walk (non-ambulation) and wheelchair reliance. Spasticity may progress to the upper extremities, leading to the partial or total loss of use of all four limbs and torso (tetraplegia). | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_91_1 | Symptoms of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | Most children with AP-4-associated HSP have:• a “floppy” appearance in infancy due to low muscle tone
• increasing spasticity and paralysis in the lower limbs starting in early childhood
• delayed motor development
• poor or absent speech development
• moderate to severe intellectual disability
• microcephaly
• seizures including frequent seizures in the setting of feverOther known features of AP-4-HSP can include the following (not every child will have these features):
• short stature
• dystonia (involuntary muscle contractions)
• ataxia (impaired balance and coordination) | Symptoms of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). Most children with AP-4-associated HSP have:• a “floppy” appearance in infancy due to low muscle tone
• increasing spasticity and paralysis in the lower limbs starting in early childhood
• delayed motor development
• poor or absent speech development
• moderate to severe intellectual disability
• microcephaly
• seizures including frequent seizures in the setting of feverOther known features of AP-4-HSP can include the following (not every child will have these features):
• short stature
• dystonia (involuntary muscle contractions)
• ataxia (impaired balance and coordination) | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_91_2 | Causes of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | AP-4-associated HSP are inherited in an autosomal recessive manner. The four genes that encode subunits of the AP-4 complex are AP4B1, AP4E1, AP4M1, and AP4S1.Recessive genetic disorders occur when an individual inherits a mutated gene from each parent. If an individual receives one normal gene and one mutated gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the mutated gene and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. | Causes of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). AP-4-associated HSP are inherited in an autosomal recessive manner. The four genes that encode subunits of the AP-4 complex are AP4B1, AP4E1, AP4M1, and AP4S1.Recessive genetic disorders occur when an individual inherits a mutated gene from each parent. If an individual receives one normal gene and one mutated gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the mutated gene and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_91_3 | Affects of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | AP-4-associated HSP affects males and females of many ethnic groups from around the world. The prevalence of AP-4-HSP is unknown. AP-4-HSP is likely under-recognized since the symptoms (phenotypic spectrum) largely overlap with that of cerebral palsy and, in the absence of genetic testing, patients may be misdiagnosed as having cerebral palsy. | Affects of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). AP-4-associated HSP affects males and females of many ethnic groups from around the world. The prevalence of AP-4-HSP is unknown. AP-4-HSP is likely under-recognized since the symptoms (phenotypic spectrum) largely overlap with that of cerebral palsy and, in the absence of genetic testing, patients may be misdiagnosed as having cerebral palsy. | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_91_4 | Related disorders of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | Many of the initial clinical manifestations of AP-4-associated HSP are nonspecific and may resemble other disorders characterized by spasticity, developmental delay / intellectual disability and seizures. Patients may be misdiagnosed as having cerebral palsy. | Related disorders of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). Many of the initial clinical manifestations of AP-4-associated HSP are nonspecific and may resemble other disorders characterized by spasticity, developmental delay / intellectual disability and seizures. Patients may be misdiagnosed as having cerebral palsy. | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_91_5 | Diagnosis of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | The diagnosis of AP-4-associated HSP is based on clinical characteristics and testing that may include a brain MRI showing characteristic features such as a thin corpus callosum, wide lateral ventricles and changes in the white matter. A definitive diagnosis is reached by genetic testing. | Diagnosis of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). The diagnosis of AP-4-associated HSP is based on clinical characteristics and testing that may include a brain MRI showing characteristic features such as a thin corpus callosum, wide lateral ventricles and changes in the white matter. A definitive diagnosis is reached by genetic testing. | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_91_6 | Therapies of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) | Management of Symptoms
Ages 0-3 years
Referral to an early intervention program is recommended for access to occupational, physical, speech and feeding therapy as well as mental health services, special educators and sensory-impairment specialists.Ages 3-5 years
In the United States, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social and/or cognitive delay. The early intervention program typically assists with this transition.Ages 5-21 years
In the United States, an IEP based on the individual’s level of function should be developed by the local public school district and will dictate specially designed instruction/related services. Discussion about transition plans including financial and medical arrangements should begin at the age of 12 years. Developmental pediatricians can help with transition to adulthood.Motor Dysfunction
Gross motor dysfunction
• Physical therapy is recommended to maximize mobility.
• Consider the use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics and adaptive strollers).Fine motor dysfunction
Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing and writing.Oral-motor dysfunction
Oral-motor dysfunction should be reassessed in regular intervals and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses or feeding refusal that is not otherwise explained.Communication Issues
Speech therapy is recommended. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties.Multidisciplinary Care
Care should be provided by a multidisciplinary care team that includes input from neurology, physiatry, orthopedics, developmental medicine and others is recommended. | Therapies of AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP). Management of Symptoms
Ages 0-3 years
Referral to an early intervention program is recommended for access to occupational, physical, speech and feeding therapy as well as mental health services, special educators and sensory-impairment specialists.Ages 3-5 years
In the United States, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social and/or cognitive delay. The early intervention program typically assists with this transition.Ages 5-21 years
In the United States, an IEP based on the individual’s level of function should be developed by the local public school district and will dictate specially designed instruction/related services. Discussion about transition plans including financial and medical arrangements should begin at the age of 12 years. Developmental pediatricians can help with transition to adulthood.Motor Dysfunction
Gross motor dysfunction
• Physical therapy is recommended to maximize mobility.
• Consider the use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics and adaptive strollers).Fine motor dysfunction
Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing and writing.Oral-motor dysfunction
Oral-motor dysfunction should be reassessed in regular intervals and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses or feeding refusal that is not otherwise explained.Communication Issues
Speech therapy is recommended. Consider evaluation for alternative means of communication (e.g., Augmentative and Alternative Communication [AAC]) for individuals who have expressive language difficulties.Multidisciplinary Care
Care should be provided by a multidisciplinary care team that includes input from neurology, physiatry, orthopedics, developmental medicine and others is recommended. | 91 | AP-4-Associated Hereditary Spastic Paraplegia (AP-4-HSP) |
nord_92_0 | Overview of Apert Syndrome | SummaryApert syndrome is a rare genetic condition that is apparent at birth. People with Apert syndrome can have distinctive malformations of the skull, face, hands, and feet. Apert syndrome is characterized by craniosynostosis, a condition in which the fibrous joints (sutures) between bones of the skull close prematurely. This can cause the top of the head to appear pointed and can affect facial bones. Certain fingers or toes may be fused or webbed. Affected children may also have intellectual disability. The severity of symptoms varies between individuals. Apert syndrome almost always results from new genetic changes (mutations) that occur randomly. Rarely, it is inherited in an autosomal dominant pattern. People with Apert syndrome can undergo therapies that address specific symptoms. This could include reconstructive skull, facial, hand, and foot surgeries.IntroductionApert syndrome is a type of acrocephalosyndactyly (ACS known as acrocephalosyndactyly type 1 (ACS1). All forms of ACS are characterized by craniosynostosis and this affects the proper growth of the skull and head. | Overview of Apert Syndrome. SummaryApert syndrome is a rare genetic condition that is apparent at birth. People with Apert syndrome can have distinctive malformations of the skull, face, hands, and feet. Apert syndrome is characterized by craniosynostosis, a condition in which the fibrous joints (sutures) between bones of the skull close prematurely. This can cause the top of the head to appear pointed and can affect facial bones. Certain fingers or toes may be fused or webbed. Affected children may also have intellectual disability. The severity of symptoms varies between individuals. Apert syndrome almost always results from new genetic changes (mutations) that occur randomly. Rarely, it is inherited in an autosomal dominant pattern. People with Apert syndrome can undergo therapies that address specific symptoms. This could include reconstructive skull, facial, hand, and foot surgeries.IntroductionApert syndrome is a type of acrocephalosyndactyly (ACS known as acrocephalosyndactyly type 1 (ACS1). All forms of ACS are characterized by craniosynostosis and this affects the proper growth of the skull and head. | 92 | Apert Syndrome |
nord_92_1 | Symptoms of Apert Syndrome | Apert syndrome is characterized by craniosynostosis, the premature closure of the fibrous joints (sutures) between certain bones in the skull. In individuals without craniosynostosis, sutures allow an infant’s head to grow and expand. Eventually, these bones fuse together to form the skull. For people with craniosynostosis, the brain is still growing after these sutures prematurely close. The pressure of brain growth can cause various bones of the skull and face to change shape during development. Depending on which sutures prematurely close, the severity can vary. In most affected individuals, there is premature closure of the sutures between the bones forming the forehead and the upper sides of the skull. This tends to cause the head to appear pointed at the top (acrocephaly) from birth. In addition, the back portion of the skull may appear flattened, with a high and broad forehead. There can be a large, late-closing “soft spot” on the skull. Individuals may also have hydrocephalus, in which cerebrospinal fluid abnormally accumulates in the cavities of the brain. This can cause pressure on the brain.The facial bones can be affected by craniosynostosis. This can lead to characteristic facial abnormalities. People with Apert syndrome may have widely spaced eyes (hypertelorism), bulging eyes, or down-slanting palpebral fissures. They may also have underdeveloped midfacial regions (maxillary hypoplasia) and palate abnormalities such as a cleft palate. The right and left sides of the face may not be symmetrical. People with Apert syndrome may have a flattened nose with a low bridge. Individuals may have delayed teeth growth, dental crowding, or an open bite. They can have moderate to severe acne. If the openings between the nose and throat are narrowed or blocked or the tracheal cartilage is malformed, this could interfere with breathing and swallowing. Individuals with these blockages can have upper respiratory tract infections, sleep apnea, and malnutrition.Apert syndrome has several characteristic hand and foot malformations. Affected individuals can have short fingers and broad thumbs and great toes that deviate outward. They may also have partial to complete fusion (syndactyly) of certain fingers and toes. Many affected people have complete fusion of the bones of the second to the fourth fingers, and one single, continuous nail (“mitten-like” syndactyly). However, other fusions can also happen. Finger joints tend to become stiff by about four years of age. In the feet, syndactyly also typically involves the second, third, and fourth toes. The toenails may be partially continuous or separate. Generally, upper limbs are more severely affected by Apert syndrome than the lower limbs.Apert syndrome can affect other organ systems as well: | Symptoms of Apert Syndrome. Apert syndrome is characterized by craniosynostosis, the premature closure of the fibrous joints (sutures) between certain bones in the skull. In individuals without craniosynostosis, sutures allow an infant’s head to grow and expand. Eventually, these bones fuse together to form the skull. For people with craniosynostosis, the brain is still growing after these sutures prematurely close. The pressure of brain growth can cause various bones of the skull and face to change shape during development. Depending on which sutures prematurely close, the severity can vary. In most affected individuals, there is premature closure of the sutures between the bones forming the forehead and the upper sides of the skull. This tends to cause the head to appear pointed at the top (acrocephaly) from birth. In addition, the back portion of the skull may appear flattened, with a high and broad forehead. There can be a large, late-closing “soft spot” on the skull. Individuals may also have hydrocephalus, in which cerebrospinal fluid abnormally accumulates in the cavities of the brain. This can cause pressure on the brain.The facial bones can be affected by craniosynostosis. This can lead to characteristic facial abnormalities. People with Apert syndrome may have widely spaced eyes (hypertelorism), bulging eyes, or down-slanting palpebral fissures. They may also have underdeveloped midfacial regions (maxillary hypoplasia) and palate abnormalities such as a cleft palate. The right and left sides of the face may not be symmetrical. People with Apert syndrome may have a flattened nose with a low bridge. Individuals may have delayed teeth growth, dental crowding, or an open bite. They can have moderate to severe acne. If the openings between the nose and throat are narrowed or blocked or the tracheal cartilage is malformed, this could interfere with breathing and swallowing. Individuals with these blockages can have upper respiratory tract infections, sleep apnea, and malnutrition.Apert syndrome has several characteristic hand and foot malformations. Affected individuals can have short fingers and broad thumbs and great toes that deviate outward. They may also have partial to complete fusion (syndactyly) of certain fingers and toes. Many affected people have complete fusion of the bones of the second to the fourth fingers, and one single, continuous nail (“mitten-like” syndactyly). However, other fusions can also happen. Finger joints tend to become stiff by about four years of age. In the feet, syndactyly also typically involves the second, third, and fourth toes. The toenails may be partially continuous or separate. Generally, upper limbs are more severely affected by Apert syndrome than the lower limbs.Apert syndrome can affect other organ systems as well: | 92 | Apert Syndrome |
nord_92_2 | Causes of Apert Syndrome | Apert syndrome is caused by a change (mutation) in the fibroblast growth factor receptor-2 (FGFR2) gene. This gene plays a critical role in skeletal development. Genes provide instructions for creating proteins that play distinct roles in our body. When a mutation of a gene occurs, the protein product may not work as it should. In Apert syndrome, mutations in FGFR2 result in these receptors not properly communicating with fibroblast growth factors. This affects the formation of normal sutures in the brain and can obstruct the development of many other structures in the body. This improper formation is what causes the malformations seen in Apert syndrome.In almost all reported patients, the disorder has been caused by one of two specific mutations of the FGFR2 gene. (These mutations are designated “Ser252Trp” and “Pro253Arg.”) These mutations may cause slightly different presentations, including the severity of syndactyly. Different mutations in the FGFR2 gene may cause several other related disorders, including Pfeiffer syndrome, Crouzon syndrome, and Jackson-Weiss syndrome. (For further information on these disorders, please see the “Related Disorders” section of this report below.)In up to 95% of patients, Apert syndrome results from a new mutation in the FGFR2 gene. These new mutations appear to occur randomly for unknown reasons (sporadically). It has been reported that sporadic cases may be associated with increased age of the father. Rarely, Apert syndrome is inherited in an autosomal dominant fashion. Dominant genetic disorders occur when only a single copy of a mutation is necessary to cause a particular disease. The risk of passing the mutation from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | Causes of Apert Syndrome. Apert syndrome is caused by a change (mutation) in the fibroblast growth factor receptor-2 (FGFR2) gene. This gene plays a critical role in skeletal development. Genes provide instructions for creating proteins that play distinct roles in our body. When a mutation of a gene occurs, the protein product may not work as it should. In Apert syndrome, mutations in FGFR2 result in these receptors not properly communicating with fibroblast growth factors. This affects the formation of normal sutures in the brain and can obstruct the development of many other structures in the body. This improper formation is what causes the malformations seen in Apert syndrome.In almost all reported patients, the disorder has been caused by one of two specific mutations of the FGFR2 gene. (These mutations are designated “Ser252Trp” and “Pro253Arg.”) These mutations may cause slightly different presentations, including the severity of syndactyly. Different mutations in the FGFR2 gene may cause several other related disorders, including Pfeiffer syndrome, Crouzon syndrome, and Jackson-Weiss syndrome. (For further information on these disorders, please see the “Related Disorders” section of this report below.)In up to 95% of patients, Apert syndrome results from a new mutation in the FGFR2 gene. These new mutations appear to occur randomly for unknown reasons (sporadically). It has been reported that sporadic cases may be associated with increased age of the father. Rarely, Apert syndrome is inherited in an autosomal dominant fashion. Dominant genetic disorders occur when only a single copy of a mutation is necessary to cause a particular disease. The risk of passing the mutation from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | 92 | Apert Syndrome |
nord_92_3 | Affects of Apert Syndrome | Apert syndrome is estimated to occur in about one in 65,000 births. Males and females seem to have Apert syndrome in relatively equal numbers. Over 300 cases have been reported since the disorder was originally described in 1894 and 1906. Asian individuals have been reported to have the highest incidence of Apert syndrome. | Affects of Apert Syndrome. Apert syndrome is estimated to occur in about one in 65,000 births. Males and females seem to have Apert syndrome in relatively equal numbers. Over 300 cases have been reported since the disorder was originally described in 1894 and 1906. Asian individuals have been reported to have the highest incidence of Apert syndrome. | 92 | Apert Syndrome |
nord_92_4 | Related disorders of Apert Syndrome | Symptoms of the following disorders may be similar to those of Apert syndrome. Comparisons may be useful for a differential diagnosis.Carpenter syndrome is a rare genetic disorder associated with craniosynostosis, webbing or fusion (syndactyly) of certain fingers or toes, and/or extra fingers or toes (polydactyly). The top of the head may appear unusually conical (acrocephaly) or the head may seem short and broad (brachycephaly). In addition, the cranial sutures often fuse unevenly, causing the head and face to appear asymmetrical from one side to the other. In some instances, additional physical abnormalities are present, such as short stature, congenital heart defects, mild to moderate obesity, umbilical hernias, or failure of the testes to descend into the scrotum in affected males. Many individuals with the disorder are affected by mild to moderate intellectual disability. Carpenter syndrome can be caused by alterations in the RAB23 gene or the MEGF8 gene. Both types of Carpenter syndrome are inherited in an autosomal recessive manner. (For more information on this disorder, choose “Carpenter” as your search term in the Rare Disease Database.)Crouzon syndrome is a rare genetic disorder associated with craniosynostosis. People with Crouzon syndrome also have midfacial malformations, protruding eyes, and airway blockages leading to breathing and swallowing difficulties. Some affected individuals have a very large head (hydrocephalus). Crouzon syndrome does not typically involve intellectual disability or problems with the arms, legs, hands, or feet. Crouzon syndrome is caused by alterations in one of the FGFR genes, usually FGFR2, and is inherited in an autosomal dominant manner. (For more information on this disorder, choose “Crouzon” as your search term in the Rare Disease Database.)Jackson-Weiss syndrome (JWS) is a rare genetic disorder that involves craniosynostosis and abnormalities of the feet. The range and severity of symptoms and findings vary greatly, even among affected members of the same family. Primary findings may include unusually flat, underdeveloped midfacial regions (midfacial hypoplasia), abnormally broad great toes, and/or malformation or fusion of certain bones within the feet. JWS can occur sporadically, or it can be inherited in an autosomal dominant pattern. Certain variants of the FGFR2 gene can cause JWS, although mutations in other genes (like FGFR3) can produce a similar appearing condition. (For more information on this disorder, choose “Jackson Weiss” as your search term in the Rare Disease Database.)Pfeiffer syndrome is a rare genetic disorder characterized by craniosynostosis and abnormally broad and medially deviated thumbs and great toes. Most affected individuals also have differences in their midface (protruding eyes) and conductive hearing loss. There are three forms of Pfeiffer syndrome. Types II and III are more serious. Pfeiffer syndrome is an autosomal dominant condition associated with mutations in the genes FGFR2 and FGFR1. (For more information on this disorder, choose “Pfeiffer” as your search term in the Rare Disease Database.)Saethre-Chotzen syndrome (SCS) is another rare genetic disorder characterized by craniosynostosis and/or webbing or fusion (syndactyly) of certain fingers or toes. In many patients, the cranial sutures may fuse unevenly, causing the sides of the head and face to appear asymmetrical. Additional variations of the skull and facial region may also be present, such as widely spaced eyes (ocular hypertelorism) with unusually shallow eye cavities; drooping of the upper eyelids; and a state where the eyes do not point in the same direction (strabismus). Some affected individuals may also have a “beaked” nose; deviation of the partition that separates the nostrils; small, low-set ears; and an underdeveloped upper jaw. The disorder is also associated with variations of the hands and feet, such as partial fusion of soft tissues (cutaneous syndactyly) of certain fingers and toes; unusually short digits; and broad great toes. Intelligence is usually normal. SCS is inherited in an autosomal dominant manner. (For more information on this disorder, choose “Saethre-Chotzen” as your search term in the Rare Disease Database.) | Related disorders of Apert Syndrome. Symptoms of the following disorders may be similar to those of Apert syndrome. Comparisons may be useful for a differential diagnosis.Carpenter syndrome is a rare genetic disorder associated with craniosynostosis, webbing or fusion (syndactyly) of certain fingers or toes, and/or extra fingers or toes (polydactyly). The top of the head may appear unusually conical (acrocephaly) or the head may seem short and broad (brachycephaly). In addition, the cranial sutures often fuse unevenly, causing the head and face to appear asymmetrical from one side to the other. In some instances, additional physical abnormalities are present, such as short stature, congenital heart defects, mild to moderate obesity, umbilical hernias, or failure of the testes to descend into the scrotum in affected males. Many individuals with the disorder are affected by mild to moderate intellectual disability. Carpenter syndrome can be caused by alterations in the RAB23 gene or the MEGF8 gene. Both types of Carpenter syndrome are inherited in an autosomal recessive manner. (For more information on this disorder, choose “Carpenter” as your search term in the Rare Disease Database.)Crouzon syndrome is a rare genetic disorder associated with craniosynostosis. People with Crouzon syndrome also have midfacial malformations, protruding eyes, and airway blockages leading to breathing and swallowing difficulties. Some affected individuals have a very large head (hydrocephalus). Crouzon syndrome does not typically involve intellectual disability or problems with the arms, legs, hands, or feet. Crouzon syndrome is caused by alterations in one of the FGFR genes, usually FGFR2, and is inherited in an autosomal dominant manner. (For more information on this disorder, choose “Crouzon” as your search term in the Rare Disease Database.)Jackson-Weiss syndrome (JWS) is a rare genetic disorder that involves craniosynostosis and abnormalities of the feet. The range and severity of symptoms and findings vary greatly, even among affected members of the same family. Primary findings may include unusually flat, underdeveloped midfacial regions (midfacial hypoplasia), abnormally broad great toes, and/or malformation or fusion of certain bones within the feet. JWS can occur sporadically, or it can be inherited in an autosomal dominant pattern. Certain variants of the FGFR2 gene can cause JWS, although mutations in other genes (like FGFR3) can produce a similar appearing condition. (For more information on this disorder, choose “Jackson Weiss” as your search term in the Rare Disease Database.)Pfeiffer syndrome is a rare genetic disorder characterized by craniosynostosis and abnormally broad and medially deviated thumbs and great toes. Most affected individuals also have differences in their midface (protruding eyes) and conductive hearing loss. There are three forms of Pfeiffer syndrome. Types II and III are more serious. Pfeiffer syndrome is an autosomal dominant condition associated with mutations in the genes FGFR2 and FGFR1. (For more information on this disorder, choose “Pfeiffer” as your search term in the Rare Disease Database.)Saethre-Chotzen syndrome (SCS) is another rare genetic disorder characterized by craniosynostosis and/or webbing or fusion (syndactyly) of certain fingers or toes. In many patients, the cranial sutures may fuse unevenly, causing the sides of the head and face to appear asymmetrical. Additional variations of the skull and facial region may also be present, such as widely spaced eyes (ocular hypertelorism) with unusually shallow eye cavities; drooping of the upper eyelids; and a state where the eyes do not point in the same direction (strabismus). Some affected individuals may also have a “beaked” nose; deviation of the partition that separates the nostrils; small, low-set ears; and an underdeveloped upper jaw. The disorder is also associated with variations of the hands and feet, such as partial fusion of soft tissues (cutaneous syndactyly) of certain fingers and toes; unusually short digits; and broad great toes. Intelligence is usually normal. SCS is inherited in an autosomal dominant manner. (For more information on this disorder, choose “Saethre-Chotzen” as your search term in the Rare Disease Database.) | 92 | Apert Syndrome |
nord_92_5 | Diagnosis of Apert Syndrome | A diagnosis of Apert syndrome is most often made at birth or during infancy. An individual is diagnosed through clinical evaluation and a variety of specialized tests. Physical features like facial anomalies or syndactyly would be identified. Skeletal abnormalities and congenital heart defects may be detected using imaging, like a computed tomography (CT) scan or an MRI. Hearing impairment may be detected during a newborn screening hearing test. Individuals may also have testing for mutations in the FGFR2 gene, which can provide a genetic diagnosis of Apert syndrome.In some instances, features of Apert syndrome may be detected before birth. This would be done through prenatal 2D or 3D ultrasound or magnetic resonance imaging (MRI). An ultrasound is a noninvasive procedure that can see an image of the fetus. This can detect differences in skull shape, facial anomalies, and syndactyly. Fetal MRI can provide greater detail of the fetal brain than ultrasound. | Diagnosis of Apert Syndrome. A diagnosis of Apert syndrome is most often made at birth or during infancy. An individual is diagnosed through clinical evaluation and a variety of specialized tests. Physical features like facial anomalies or syndactyly would be identified. Skeletal abnormalities and congenital heart defects may be detected using imaging, like a computed tomography (CT) scan or an MRI. Hearing impairment may be detected during a newborn screening hearing test. Individuals may also have testing for mutations in the FGFR2 gene, which can provide a genetic diagnosis of Apert syndrome.In some instances, features of Apert syndrome may be detected before birth. This would be done through prenatal 2D or 3D ultrasound or magnetic resonance imaging (MRI). An ultrasound is a noninvasive procedure that can see an image of the fetus. This can detect differences in skull shape, facial anomalies, and syndactyly. Fetal MRI can provide greater detail of the fetal brain than ultrasound. | 92 | Apert Syndrome |
nord_92_6 | Therapies of Apert Syndrome | TreatmentThe treatment of Apert syndrome varies based on which symptoms are seen in the individual. Such treatment may require care by a team of healthcare providers including pediatricians and surgeons. Specialists may include hearing specialists, neurosurgeons, physicians who specialize in disorders of the skeleton, joints, and muscles (orthopedists), physicians who specialize in disorders of the ears, nose, and throat (otolaryngologists), and physicians who specialize in heart abnormalities (cardiologists).Specific therapies for Apert syndrome are symptomatic and supportive. Craniosynostosis and hydrocephalus may result in abnormally increased pressure within the skull and on the brain. In such cases, early surgery (within 2 to 4 months after birth) may be advised to correct craniosynostosis. For those with hydrocephalus, surgery may also involve inserting a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain. The CSF would be drained into another part of the body where it can be absorbed. Corrective and reconstructive surgery may be recommended to help correct craniofacial malformations. Surgery may also be able to help correct polydactyly and syndactyly, and other skeletal defects or physical abnormalities. For those with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be necessary. For some individuals with hearing impairment, hearing aids may be beneficial. Early intervention may be important to ensure that children with Apert syndrome reach their full potential. Special services like physical therapy, occupational therapy, and special education may be beneficial.Genetic counseling is recommended for affected individuals and their families. A genetic counselor can explain the causes of Apert syndrome. They can also discuss the chances of having additional children with Apert syndrome. Psychosocial support for the entire family is essential as well. | Therapies of Apert Syndrome. TreatmentThe treatment of Apert syndrome varies based on which symptoms are seen in the individual. Such treatment may require care by a team of healthcare providers including pediatricians and surgeons. Specialists may include hearing specialists, neurosurgeons, physicians who specialize in disorders of the skeleton, joints, and muscles (orthopedists), physicians who specialize in disorders of the ears, nose, and throat (otolaryngologists), and physicians who specialize in heart abnormalities (cardiologists).Specific therapies for Apert syndrome are symptomatic and supportive. Craniosynostosis and hydrocephalus may result in abnormally increased pressure within the skull and on the brain. In such cases, early surgery (within 2 to 4 months after birth) may be advised to correct craniosynostosis. For those with hydrocephalus, surgery may also involve inserting a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain. The CSF would be drained into another part of the body where it can be absorbed. Corrective and reconstructive surgery may be recommended to help correct craniofacial malformations. Surgery may also be able to help correct polydactyly and syndactyly, and other skeletal defects or physical abnormalities. For those with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be necessary. For some individuals with hearing impairment, hearing aids may be beneficial. Early intervention may be important to ensure that children with Apert syndrome reach their full potential. Special services like physical therapy, occupational therapy, and special education may be beneficial.Genetic counseling is recommended for affected individuals and their families. A genetic counselor can explain the causes of Apert syndrome. They can also discuss the chances of having additional children with Apert syndrome. Psychosocial support for the entire family is essential as well. | 92 | Apert Syndrome |
nord_93_0 | Overview of Aplasia Cutis Congenita | Aplasia Cutis Congenita is a rare disorder with a complicated pattern of inheritance. Babies are born with the absence of certain layer(s) of skin, most often on the scalp, but also on the trunk, and/or arms and legs. The affected area is typically covered with a thin, transparent membrane. The skull and/or underlying areas may be visible and be abnormally developed. Aplasia Cutis Congenita may be the primary disorder or it may occur in association with other underlying disorders. | Overview of Aplasia Cutis Congenita. Aplasia Cutis Congenita is a rare disorder with a complicated pattern of inheritance. Babies are born with the absence of certain layer(s) of skin, most often on the scalp, but also on the trunk, and/or arms and legs. The affected area is typically covered with a thin, transparent membrane. The skull and/or underlying areas may be visible and be abnormally developed. Aplasia Cutis Congenita may be the primary disorder or it may occur in association with other underlying disorders. | 93 | Aplasia Cutis Congenita |
nord_93_1 | Symptoms of Aplasia Cutis Congenita | Individuals born with Aplasia Cutis Congenita lack skin (and therefore hair), in localized areas of the body, usually, but not always, on the scalp (70 percent of cases). In some cases, the trunk, arms, and/or legs may also be involved. Sometimes, the underlying bone may be missing as well as the skin. The affected area(s) are usually replaced with a thin transparent membrane. In some cases, these affected structures and other organs may be seen through the transparent membrane. Most individuals with Aplasia Cutis Congenita exhibit no other abnormalities. However, in some rare cases, they may experience other physical characteristics including abnormalities of the ears, a form of paralysis (palsy) affecting one side of the face, an abnormally large head (macrocephaly), and/or congenital heart anomalies. Aplasia Cutis Congenita may also occur as a physical condition characteristic of several other disorders, including Adams-Oliver Syndrome, Aplasia Cutis Congenita-Gastrointestinal, and Johanson-Blizzard Syndrome. (For more information on these disorders, see the Related Disorders section of this report.) | Symptoms of Aplasia Cutis Congenita. Individuals born with Aplasia Cutis Congenita lack skin (and therefore hair), in localized areas of the body, usually, but not always, on the scalp (70 percent of cases). In some cases, the trunk, arms, and/or legs may also be involved. Sometimes, the underlying bone may be missing as well as the skin. The affected area(s) are usually replaced with a thin transparent membrane. In some cases, these affected structures and other organs may be seen through the transparent membrane. Most individuals with Aplasia Cutis Congenita exhibit no other abnormalities. However, in some rare cases, they may experience other physical characteristics including abnormalities of the ears, a form of paralysis (palsy) affecting one side of the face, an abnormally large head (macrocephaly), and/or congenital heart anomalies. Aplasia Cutis Congenita may also occur as a physical condition characteristic of several other disorders, including Adams-Oliver Syndrome, Aplasia Cutis Congenita-Gastrointestinal, and Johanson-Blizzard Syndrome. (For more information on these disorders, see the Related Disorders section of this report.) | 93 | Aplasia Cutis Congenita |
nord_93_2 | Causes of Aplasia Cutis Congenita | Aplasia Cutis Congenita is a rare disorder that may be inherited as an autosomal dominant or autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy. | Causes of Aplasia Cutis Congenita. Aplasia Cutis Congenita is a rare disorder that may be inherited as an autosomal dominant or autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy. | 93 | Aplasia Cutis Congenita |
nord_93_3 | Affects of Aplasia Cutis Congenita | Aplasia Cutis Congenita is a very rare disorder that affects males and females in equal numbers. At least five hundred cases have been reported in the medical literature. Absence of skin is obvious at birth (congenital). | Affects of Aplasia Cutis Congenita. Aplasia Cutis Congenita is a very rare disorder that affects males and females in equal numbers. At least five hundred cases have been reported in the medical literature. Absence of skin is obvious at birth (congenital). | 93 | Aplasia Cutis Congenita |
nord_93_4 | Related disorders of Aplasia Cutis Congenita | Aplasia Cutis Congenita may be one of the symptoms of the following disorders.Adams-Oliver Syndrome is a rare inherited disorder characterized by the absence of bone in areas of the skull and bald ulcerated areas of overlying scalp. These skull and scalp abnormalities usually heal spontaneously during the first few months of life, but in a few cases plastic surgery may be necessary. Limb abnormalities may vary in severity. Fingers and toes may be absent or shorter than normal, and the longer bones in the hand may be absent. In some severe cases, the leg below the midcalf may be absent. (For more information on this disorder choose “Adams-Oliver Syndrome” as your search term in the Rare Disease Database.)Aplasia Cutis Congenita-Gastrointestinal is a rare disorder inherited as an autosomal recessive trait. This disorder is characterized by extensive Aplasia Cutis Congenita and the absence of a normal opening in the canal that goes from below the mouth to the stomach (esophagus), the tube-shaped part of the stomach, and/or the short part of the small intestine that joins the stomach (duodenum). Other symptoms found in some patients with Aplasia Cutis Congenita-Gastrointestinal may be skin separation and/or low-set ears. This disorder is rapidly progressive.Johanson-Blizzard Syndrome is a form of ectodermal dysplasia that is characterized by nose, scalp and hair defects, as well as a lack of teeth, deafness, short stature, a lack of motor development and malabsorption problems. The most striking feature of this syndrome is the beaklike appearance of the nose. Three-fourths of the patients have a protrusion over the rear fontanelle of the skull at birth which gets thick and hard as the child grows. Their teeth are peg-shaped and they have thin hair that sweeps up from the forehead. Patients with Johanson-Blizzard Syndrome show marked hearing loss from birth as well as motor and mental retardation. Bone growth is delayed and there may be associated intestinal, absorption and genital defects. (For more information on this disorder choose “Ectodermal Dysplasia”as your search term in the Rare Disease Database.) | Related disorders of Aplasia Cutis Congenita. Aplasia Cutis Congenita may be one of the symptoms of the following disorders.Adams-Oliver Syndrome is a rare inherited disorder characterized by the absence of bone in areas of the skull and bald ulcerated areas of overlying scalp. These skull and scalp abnormalities usually heal spontaneously during the first few months of life, but in a few cases plastic surgery may be necessary. Limb abnormalities may vary in severity. Fingers and toes may be absent or shorter than normal, and the longer bones in the hand may be absent. In some severe cases, the leg below the midcalf may be absent. (For more information on this disorder choose “Adams-Oliver Syndrome” as your search term in the Rare Disease Database.)Aplasia Cutis Congenita-Gastrointestinal is a rare disorder inherited as an autosomal recessive trait. This disorder is characterized by extensive Aplasia Cutis Congenita and the absence of a normal opening in the canal that goes from below the mouth to the stomach (esophagus), the tube-shaped part of the stomach, and/or the short part of the small intestine that joins the stomach (duodenum). Other symptoms found in some patients with Aplasia Cutis Congenita-Gastrointestinal may be skin separation and/or low-set ears. This disorder is rapidly progressive.Johanson-Blizzard Syndrome is a form of ectodermal dysplasia that is characterized by nose, scalp and hair defects, as well as a lack of teeth, deafness, short stature, a lack of motor development and malabsorption problems. The most striking feature of this syndrome is the beaklike appearance of the nose. Three-fourths of the patients have a protrusion over the rear fontanelle of the skull at birth which gets thick and hard as the child grows. Their teeth are peg-shaped and they have thin hair that sweeps up from the forehead. Patients with Johanson-Blizzard Syndrome show marked hearing loss from birth as well as motor and mental retardation. Bone growth is delayed and there may be associated intestinal, absorption and genital defects. (For more information on this disorder choose “Ectodermal Dysplasia”as your search term in the Rare Disease Database.) | 93 | Aplasia Cutis Congenita |
nord_93_5 | Diagnosis of Aplasia Cutis Congenita | Diagnosis of Aplasia Cutis Congenita. | 93 | Aplasia Cutis Congenita |
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nord_93_6 | Therapies of Aplasia Cutis Congenita | Diagnosis of Aplasia Cutis Congenita is generally obvious at birth through the characteristic absence of skin affecting the scalp, trunk, arms, and/or legs.Children diagnosed with Aplasia Cutis Congenita should receive a complete medical evaluation to determine whether this disorder is occurring on its own or as a secondary characteristic of another disorder. If Aplasia Cutis Congenita is occurring on its own, affected children should be monitored for symptoms and physical characteristics associated with this disorder.Medical treatments of Aplasia Cutis Congenita include measures to prevent the drying out of the membrane by soothing, bland ointments. Antibiotics should be used only if signs of bacterial infection are present. The damaged area usually heals spontaneously.Surgical care may include the repair of multiple scalp defects that usually, but not always, respond to procedures less traumatic than skin grafts. These may include such techniques as tissue expanders to fill in large areas or flap rotation to ease a piece of skin over an affected area.Genetic counseling may be of benefit for affected individuals and their families. | Therapies of Aplasia Cutis Congenita. Diagnosis of Aplasia Cutis Congenita is generally obvious at birth through the characteristic absence of skin affecting the scalp, trunk, arms, and/or legs.Children diagnosed with Aplasia Cutis Congenita should receive a complete medical evaluation to determine whether this disorder is occurring on its own or as a secondary characteristic of another disorder. If Aplasia Cutis Congenita is occurring on its own, affected children should be monitored for symptoms and physical characteristics associated with this disorder.Medical treatments of Aplasia Cutis Congenita include measures to prevent the drying out of the membrane by soothing, bland ointments. Antibiotics should be used only if signs of bacterial infection are present. The damaged area usually heals spontaneously.Surgical care may include the repair of multiple scalp defects that usually, but not always, respond to procedures less traumatic than skin grafts. These may include such techniques as tissue expanders to fill in large areas or flap rotation to ease a piece of skin over an affected area.Genetic counseling may be of benefit for affected individuals and their families. | 93 | Aplasia Cutis Congenita |
nord_94_0 | Overview of Apnea, Infantile | Apnea is a term used to describe the temporary absence of spontaneous breathing. Infantile apnea occurs in children under the age of one year. Apnea may occur because of neurological impairment of the respiratory rhythm or obstruction of air flow through the air passages. The symptoms of infantile apnea include the stoppage of breathing during sleep, an abnormal bluish discoloration to the skin (cyanosis) and sometimes an unusually slow heartbeat (bradycardia). Infantile apnea may be related to some cases of sudden infant death syndrome. Episodes of apnea may decrease with age. However, several forms of adult sleep apnea also exist. | Overview of Apnea, Infantile. Apnea is a term used to describe the temporary absence of spontaneous breathing. Infantile apnea occurs in children under the age of one year. Apnea may occur because of neurological impairment of the respiratory rhythm or obstruction of air flow through the air passages. The symptoms of infantile apnea include the stoppage of breathing during sleep, an abnormal bluish discoloration to the skin (cyanosis) and sometimes an unusually slow heartbeat (bradycardia). Infantile apnea may be related to some cases of sudden infant death syndrome. Episodes of apnea may decrease with age. However, several forms of adult sleep apnea also exist. | 94 | Apnea, Infantile |
nord_94_1 | Symptoms of Apnea, Infantile | The symptoms of infantile apnea include the temporary cessation of breathing; an abnormal bluish discoloration of the skin, lips, and mouth (cyanosis), and/or an unusually slow heartbeat (bradycardia). Serious apnea is defined as the cessation of breathing during sleep for longer than 10 to 15 seconds.Infantile sleep apnea may occur in several forms. The normal rate of respiration is regulated by groups of nerve cells in the brain. They control the rhythm of breathing in response to changing oxygen levels in the blood (respiratory drive). In central apnea, the respiratory drive is low and, during apneic episodes, there are no chest movements and no air passes through the mouth or nostrils. In this form of the disease, the brain does not send adequate signals to the diaphragm and lungs. Breathing stops and does not resume until the oxygen-starved brain sends impulses to the diaphragm and lungs. In obstructive apnea (upper airway apnea), the airway is blocked and breathing may become difficult. Blockage may occur for a variety of reasons including collapse of the soft tissues of the throat. In this form of apnea, chest movements are present, but there is no air flow into the lungs. When breathing resumes, infants may make a loud “snorting noise” and become aroused from sleep. Obstructive apnea does not involve the cessation of breathing; rather, the affected infant struggles to breath and has increased respiratory effort. Central apnea followed by or together with obstructive apnea is known as mixed apnea.Some research indicates that in many cases the symptoms of infantile apnea may decrease with advancing age. | Symptoms of Apnea, Infantile. The symptoms of infantile apnea include the temporary cessation of breathing; an abnormal bluish discoloration of the skin, lips, and mouth (cyanosis), and/or an unusually slow heartbeat (bradycardia). Serious apnea is defined as the cessation of breathing during sleep for longer than 10 to 15 seconds.Infantile sleep apnea may occur in several forms. The normal rate of respiration is regulated by groups of nerve cells in the brain. They control the rhythm of breathing in response to changing oxygen levels in the blood (respiratory drive). In central apnea, the respiratory drive is low and, during apneic episodes, there are no chest movements and no air passes through the mouth or nostrils. In this form of the disease, the brain does not send adequate signals to the diaphragm and lungs. Breathing stops and does not resume until the oxygen-starved brain sends impulses to the diaphragm and lungs. In obstructive apnea (upper airway apnea), the airway is blocked and breathing may become difficult. Blockage may occur for a variety of reasons including collapse of the soft tissues of the throat. In this form of apnea, chest movements are present, but there is no air flow into the lungs. When breathing resumes, infants may make a loud “snorting noise” and become aroused from sleep. Obstructive apnea does not involve the cessation of breathing; rather, the affected infant struggles to breath and has increased respiratory effort. Central apnea followed by or together with obstructive apnea is known as mixed apnea.Some research indicates that in many cases the symptoms of infantile apnea may decrease with advancing age. | 94 | Apnea, Infantile |
nord_94_2 | Causes of Apnea, Infantile | The exact cause of infantile apnea is not known. It may occur as the result of a combination of environmental and developmental factors (multifactoral). In extremely rare cases, central infantile apnea may be familial and affect more family members than would otherwise be expected. | Causes of Apnea, Infantile. The exact cause of infantile apnea is not known. It may occur as the result of a combination of environmental and developmental factors (multifactoral). In extremely rare cases, central infantile apnea may be familial and affect more family members than would otherwise be expected. | 94 | Apnea, Infantile |
nord_94_3 | Affects of Apnea, Infantile | Infantile apnea affects males and females in equal numbers and occurs in children less than 1 year old. Infants who are born prematurely tend to experience episodes of apnea (apnea of prematurity). | Affects of Apnea, Infantile. Infantile apnea affects males and females in equal numbers and occurs in children less than 1 year old. Infants who are born prematurely tend to experience episodes of apnea (apnea of prematurity). | 94 | Apnea, Infantile |
nord_94_4 | Related disorders of Apnea, Infantile | Symptoms of the following disorders can be similar to those of infantile apnea. Comparisons may be useful for a differential diagnosis:Sudden infant death syndrome (SIDS) is the sudden death of any infant or young child that is unexpected, based on their medical history and for which no adequate cause for death can be found. Infants are not breathing during a time when they are presumed to be sleeping. The exact relationship between sudden infant death syndrome and infantile apnea is not clear. (For more information on this disorder, choose “sudden infant death” as your search term in the Rare Disease Database.)Apnea in infants may occur for many reasons. Infants who are born prematurely (less than 34 weeks' gestation) may experience episodes of apnea. It is also important to rule out other causes of apnea such as Hypoglycemia, Sepsis, Meningitis, Hyaline Membrane Disease, Arnold Chiari Syndrome, Down's Syndrome, enlarged adenoids, anemia, gastro-esophageal reflux, craniofacial abnormalities, Zellwenger Syndrome, Holoprosencephaly, Alpers Syndrome, Schinzel-Giedion Syndrome, chromosomal abnormalities, and intracranial hemorrhage. (For more information on these disorders, choose “Hypoglycemia”, “Meningitis”, “Arnold Chiari”, “Zellwenger”, “Holoprosencephaly”, “Alpers”, “Schinzel-Giedion” and “Chromosomal” as your search terms in the Rare Disease Database.) | Related disorders of Apnea, Infantile. Symptoms of the following disorders can be similar to those of infantile apnea. Comparisons may be useful for a differential diagnosis:Sudden infant death syndrome (SIDS) is the sudden death of any infant or young child that is unexpected, based on their medical history and for which no adequate cause for death can be found. Infants are not breathing during a time when they are presumed to be sleeping. The exact relationship between sudden infant death syndrome and infantile apnea is not clear. (For more information on this disorder, choose “sudden infant death” as your search term in the Rare Disease Database.)Apnea in infants may occur for many reasons. Infants who are born prematurely (less than 34 weeks' gestation) may experience episodes of apnea. It is also important to rule out other causes of apnea such as Hypoglycemia, Sepsis, Meningitis, Hyaline Membrane Disease, Arnold Chiari Syndrome, Down's Syndrome, enlarged adenoids, anemia, gastro-esophageal reflux, craniofacial abnormalities, Zellwenger Syndrome, Holoprosencephaly, Alpers Syndrome, Schinzel-Giedion Syndrome, chromosomal abnormalities, and intracranial hemorrhage. (For more information on these disorders, choose “Hypoglycemia”, “Meningitis”, “Arnold Chiari”, “Zellwenger”, “Holoprosencephaly”, “Alpers”, “Schinzel-Giedion” and “Chromosomal” as your search terms in the Rare Disease Database.) | 94 | Apnea, Infantile |
nord_94_5 | Diagnosis of Apnea, Infantile | Diagnosis of Apnea, Infantile. | 94 | Apnea, Infantile |
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nord_94_6 | Therapies of Apnea, Infantile | To help prevent the potentially severe complications of infantile apnea, home apnea and cardiac monitors can alert a parent or caregiver to an episode of symptoms. These devices should be purchased only under the advice of a physician who is knowledgeable about the safety and effectiveness of apnea and cardiac monitors. Treatment may sometimes include the administration of drugs that stimulate the respiratory system (i.e., theophylline or caffeine). Parents and caregivers should be knowledgeable in lifesaving techniques such as cardiopulmonary resuscitation (CPR). In some infants, overheating should be avoided to possibly help reduce the frequency of apneic episodes. The infant should sleep in a supine position, unless he/she has obstructive sleep apnea or gastroesophageal reflux.If the symptoms of infantile apnea are severe, the drug aminophylline or another xanthine medication may be prescribed. Oxygen may be supplied as needed. For those infants with obstructive or mixed apnea, a medical device known as a continuous positive airway pressure (CPAP) may be used to assist regular breathing. A mask is placed on the infant's nose and is connected through a tube to the CPAP device. This machine forces air through the tube at low pressure that is sufficient to keep the infant's upper airway open and to allow air to enter the lungs. | Therapies of Apnea, Infantile. To help prevent the potentially severe complications of infantile apnea, home apnea and cardiac monitors can alert a parent or caregiver to an episode of symptoms. These devices should be purchased only under the advice of a physician who is knowledgeable about the safety and effectiveness of apnea and cardiac monitors. Treatment may sometimes include the administration of drugs that stimulate the respiratory system (i.e., theophylline or caffeine). Parents and caregivers should be knowledgeable in lifesaving techniques such as cardiopulmonary resuscitation (CPR). In some infants, overheating should be avoided to possibly help reduce the frequency of apneic episodes. The infant should sleep in a supine position, unless he/she has obstructive sleep apnea or gastroesophageal reflux.If the symptoms of infantile apnea are severe, the drug aminophylline or another xanthine medication may be prescribed. Oxygen may be supplied as needed. For those infants with obstructive or mixed apnea, a medical device known as a continuous positive airway pressure (CPAP) may be used to assist regular breathing. A mask is placed on the infant's nose and is connected through a tube to the CPAP device. This machine forces air through the tube at low pressure that is sufficient to keep the infant's upper airway open and to allow air to enter the lungs. | 94 | Apnea, Infantile |
nord_95_0 | Overview of Appendiceal Cancer and Tumors | SummaryCancers and tumors (neoplasms) of the appendix are extremely rare with an estimated incidence of 0.15-0.9 per 100,000 people. The average age of onset is between 50 and 55 years, and they affect men and women equally. They most typically present either as appendicitis, a hernia filled with mucin, increasing abdominal girth, abdominal discomfort, an abdominal/pelvic mass, as an incidental finding on some form of imaging or at the time of surgery for a different indication. In women, they often spread to the ovaries and can be easily confused with ovarian cancer. Making the diagnosis of appendiceal cancer requires examination of a tumor specimen. After starting in the appendix, appendiceal tumors and cancers frequently spread inside the abdominal cavity. Depending on the type of tumor or cancer, this can lead to either the build-up of mucinous fluid in the abdomen known as pseudomyxoma peritonei (see separate Rare Disease Report) or a condition referred to as peritoneal carcinomatosis (growth of cancer cells in the abdominal cavity—see Related Disorders section). Treatment for appendiceal tumors and cancers varies depending on the stage (extent) of disease and the subtype.IntroductionIn addition to being quite rare, cancers and tumors of the appendix come in a wide variety of types. The most common type of tumor or cancer that occurs in the appendix is a neuroendocrine or carcinoid tumor. Neuroendocrine tumors (NETs) are derived from specialized cells that reside in the wall of the appendix or other part of the intestine called enterochromaffin (EC) cells. EC cells make chemicals that help facilitate gastrointestinal motility and digestion. NETs (or carcinoid cancers) of the appendix have a unique tumor biology and are treated differently than epithelial tumors or cancers of the appendix which arise from gland-forming cells lining the inside of the appendix. One of the functions of epithelial cells is to make mucin – a jelly-like substance that helps protect the lining of the intestine.Epithelial tumors and cancers of the appendix are further categorized based upon how the cells look microscopically and whether or not they are invading the wall of the appendix. The main categories include goblet cell carcinoid (see separate Rare Disease Report), low-grade mucinous neoplasm of the appendix (LAMN), high-grade mucinous neoplasm of the appendix (HAMN) and adenocarcinomas. The adenocarcinomas are further classified as: well- differentiated, moderately-differentiated, poorly-differentiated and signet ring cell (SRC). These classifications are important for determining prognosis and treatment recommendations. | Overview of Appendiceal Cancer and Tumors. SummaryCancers and tumors (neoplasms) of the appendix are extremely rare with an estimated incidence of 0.15-0.9 per 100,000 people. The average age of onset is between 50 and 55 years, and they affect men and women equally. They most typically present either as appendicitis, a hernia filled with mucin, increasing abdominal girth, abdominal discomfort, an abdominal/pelvic mass, as an incidental finding on some form of imaging or at the time of surgery for a different indication. In women, they often spread to the ovaries and can be easily confused with ovarian cancer. Making the diagnosis of appendiceal cancer requires examination of a tumor specimen. After starting in the appendix, appendiceal tumors and cancers frequently spread inside the abdominal cavity. Depending on the type of tumor or cancer, this can lead to either the build-up of mucinous fluid in the abdomen known as pseudomyxoma peritonei (see separate Rare Disease Report) or a condition referred to as peritoneal carcinomatosis (growth of cancer cells in the abdominal cavity—see Related Disorders section). Treatment for appendiceal tumors and cancers varies depending on the stage (extent) of disease and the subtype.IntroductionIn addition to being quite rare, cancers and tumors of the appendix come in a wide variety of types. The most common type of tumor or cancer that occurs in the appendix is a neuroendocrine or carcinoid tumor. Neuroendocrine tumors (NETs) are derived from specialized cells that reside in the wall of the appendix or other part of the intestine called enterochromaffin (EC) cells. EC cells make chemicals that help facilitate gastrointestinal motility and digestion. NETs (or carcinoid cancers) of the appendix have a unique tumor biology and are treated differently than epithelial tumors or cancers of the appendix which arise from gland-forming cells lining the inside of the appendix. One of the functions of epithelial cells is to make mucin – a jelly-like substance that helps protect the lining of the intestine.Epithelial tumors and cancers of the appendix are further categorized based upon how the cells look microscopically and whether or not they are invading the wall of the appendix. The main categories include goblet cell carcinoid (see separate Rare Disease Report), low-grade mucinous neoplasm of the appendix (LAMN), high-grade mucinous neoplasm of the appendix (HAMN) and adenocarcinomas. The adenocarcinomas are further classified as: well- differentiated, moderately-differentiated, poorly-differentiated and signet ring cell (SRC). These classifications are important for determining prognosis and treatment recommendations. | 95 | Appendiceal Cancer and Tumors |
nord_95_1 | Symptoms of Appendiceal Cancer and Tumors | At the time of diagnosis, appendiceal cancer can be either localized to the appendix or have spread to other parts of the body – particularly the abdominal cavity or peritoneum. For appendiceal cancers that are localized, the most common signs and symptoms are those of acute appendicitis – namely right lower abdominal pain. For appendiceal cancers that have already spread away from the appendix, the most common presenting signs and symptoms are vague abdominal discomfort and increasing abdominal girth. In men, the first presenting sign may be a hernia that gets distended by mucin. In women, the first presenting sign may be a pelvic mass that is presumed to be ovarian cancer. Due to the very thin wall of the appendix, finding appendiceal cancer that has already spread at the time of diagnosis is more common than finding it confined to the appendix.Due to the structure of the appendix (a long, thin-walled, finger-like projection off the right colon), it is easy for tumor or cancer cells to break through the wall and spread in the abdominal cavity. Consequently, most appendiceal cancers, even the less aggressive ones, tend to present at an advanced stage with peritoneal carcinomatosis. Once the cancer cells have spread, they continue to grow and may cause abdominal discomfort, distention, a fluid build-up called ascites or pseudomyoma peritonei (mucinous ascites), and intestinal blockage or dysfunction. Over time this can lead to decreased appetite, early satiety (feeling full after eating only a small amount), nausea and vomiting.Appendiceal cancers rarely spread outside the abdominal cavity, and it is most commonly seen in poorly-differentiated or signet ring cell (SRC) cancers. However, once the cancer cells escape from the appendix, they can continue to grow in the abdominal cavity, on the surface of other organs such as the omentum, intestines, ovaries, uterus, liver, spleen and peritoneum (lining of the abdominal cavity). This condition is called peritoneal carcinomatosis (see Related Disorders) – which means growth of cancer cells within the abdominal cavity. Over time, without treatment, this condition can result in blockage of the intestines or loss of intestinal function. | Symptoms of Appendiceal Cancer and Tumors. At the time of diagnosis, appendiceal cancer can be either localized to the appendix or have spread to other parts of the body – particularly the abdominal cavity or peritoneum. For appendiceal cancers that are localized, the most common signs and symptoms are those of acute appendicitis – namely right lower abdominal pain. For appendiceal cancers that have already spread away from the appendix, the most common presenting signs and symptoms are vague abdominal discomfort and increasing abdominal girth. In men, the first presenting sign may be a hernia that gets distended by mucin. In women, the first presenting sign may be a pelvic mass that is presumed to be ovarian cancer. Due to the very thin wall of the appendix, finding appendiceal cancer that has already spread at the time of diagnosis is more common than finding it confined to the appendix.Due to the structure of the appendix (a long, thin-walled, finger-like projection off the right colon), it is easy for tumor or cancer cells to break through the wall and spread in the abdominal cavity. Consequently, most appendiceal cancers, even the less aggressive ones, tend to present at an advanced stage with peritoneal carcinomatosis. Once the cancer cells have spread, they continue to grow and may cause abdominal discomfort, distention, a fluid build-up called ascites or pseudomyoma peritonei (mucinous ascites), and intestinal blockage or dysfunction. Over time this can lead to decreased appetite, early satiety (feeling full after eating only a small amount), nausea and vomiting.Appendiceal cancers rarely spread outside the abdominal cavity, and it is most commonly seen in poorly-differentiated or signet ring cell (SRC) cancers. However, once the cancer cells escape from the appendix, they can continue to grow in the abdominal cavity, on the surface of other organs such as the omentum, intestines, ovaries, uterus, liver, spleen and peritoneum (lining of the abdominal cavity). This condition is called peritoneal carcinomatosis (see Related Disorders) – which means growth of cancer cells within the abdominal cavity. Over time, without treatment, this condition can result in blockage of the intestines or loss of intestinal function. | 95 | Appendiceal Cancer and Tumors |
nord_95_2 | Causes of Appendiceal Cancer and Tumors | The exact cause of appendiceal cancer is unknown. There are no genetic, familial or environmental factors known to cause this disorder. It does not run in families. One study has shown a correlation with the presence of the intestinal bacterium Helicobacter pylori and pseudomyoma peritonei from appendiceal neoplasms. This has prompted a clinical trial using antibiotic therapy to eradicate the bacteria. This study is still on-going at the time of this report. Recent studies have shown that appendiceal cancer do have a unique genomic profile distinct from adenocarcinomas of the colon which may offer future, appendix-specific and targetable pathways for treatment. | Causes of Appendiceal Cancer and Tumors. The exact cause of appendiceal cancer is unknown. There are no genetic, familial or environmental factors known to cause this disorder. It does not run in families. One study has shown a correlation with the presence of the intestinal bacterium Helicobacter pylori and pseudomyoma peritonei from appendiceal neoplasms. This has prompted a clinical trial using antibiotic therapy to eradicate the bacteria. This study is still on-going at the time of this report. Recent studies have shown that appendiceal cancer do have a unique genomic profile distinct from adenocarcinomas of the colon which may offer future, appendix-specific and targetable pathways for treatment. | 95 | Appendiceal Cancer and Tumors |
nord_95_3 | Affects of Appendiceal Cancer and Tumors | Appendiceal cancer is very rare with approximately 1-2 cases per 1 million individuals. Appendiceal cancers can occur at any age, with the peak occurrence in the 6th decade (average age of 50 at diagnosis). Most studies report that men and women are affected in equal numbers, while a few have suggested a slightly increased frequency in women. | Affects of Appendiceal Cancer and Tumors. Appendiceal cancer is very rare with approximately 1-2 cases per 1 million individuals. Appendiceal cancers can occur at any age, with the peak occurrence in the 6th decade (average age of 50 at diagnosis). Most studies report that men and women are affected in equal numbers, while a few have suggested a slightly increased frequency in women. | 95 | Appendiceal Cancer and Tumors |
nord_95_4 | Related disorders of Appendiceal Cancer and Tumors | Peritoneal carcinomatosis is the spread and growth of cancer cells in the abdominal cavity. Cancers that are most frequently associated with peritoneal carcinomatosis include the gastrointestinal (colon, rectal, appendiceal, gastric, pancreas, small bowel and gallbladder) and the gynecologic (ovarian, primary peritoneal, and uterine) cancers. Other cancers that can spread to the abdominal cavity include breast, esophagus, and melanoma. Gastrointestinal stromal tumors (GISTs) are a subtype of sarcoma of the intestine that can also present with multiple cancer tumors in the abdomen. Peritoneal mesothelioma is a cancer that originates in the lining of the abdominal cavity (peritoneum) and presents with signs and symptoms of peritoneal carcinomatosis. | Related disorders of Appendiceal Cancer and Tumors. Peritoneal carcinomatosis is the spread and growth of cancer cells in the abdominal cavity. Cancers that are most frequently associated with peritoneal carcinomatosis include the gastrointestinal (colon, rectal, appendiceal, gastric, pancreas, small bowel and gallbladder) and the gynecologic (ovarian, primary peritoneal, and uterine) cancers. Other cancers that can spread to the abdominal cavity include breast, esophagus, and melanoma. Gastrointestinal stromal tumors (GISTs) are a subtype of sarcoma of the intestine that can also present with multiple cancer tumors in the abdomen. Peritoneal mesothelioma is a cancer that originates in the lining of the abdominal cavity (peritoneum) and presents with signs and symptoms of peritoneal carcinomatosis. | 95 | Appendiceal Cancer and Tumors |
nord_95_5 | Diagnosis of Appendiceal Cancer and Tumors | Because there are no unique features of appendiceal cancer on imaging studies such as ultrasound, CT scan, PET scan or MRI, the actual diagnosis of appendiceal cancer cannot be made until a tumor specimen is examined by a pathologist. This is frequently accomplished at the time of appendectomy for appendicitis, surgery for an intestinal blockage or presumed ovarian cancer, or through a diagnostic tumor biopsy performed for an abnormal clinical or radiographic finding such as a palpable tumor or tumors seen on an imaging study. The finding of a dilated, mucin filled appendix on CT scan or MRI should prompt concern for an appendiceal tumor and an appendectomy should be considered. The different types of appendiceal tumors and cancers can be distinguished by the appearance of the cells under the microscope and by staining them for specific markers. Goblet cell carcinoid tumors tend to be easier to identify because of the unique combination of neuroendocrine and epithelial cells. | Diagnosis of Appendiceal Cancer and Tumors. Because there are no unique features of appendiceal cancer on imaging studies such as ultrasound, CT scan, PET scan or MRI, the actual diagnosis of appendiceal cancer cannot be made until a tumor specimen is examined by a pathologist. This is frequently accomplished at the time of appendectomy for appendicitis, surgery for an intestinal blockage or presumed ovarian cancer, or through a diagnostic tumor biopsy performed for an abnormal clinical or radiographic finding such as a palpable tumor or tumors seen on an imaging study. The finding of a dilated, mucin filled appendix on CT scan or MRI should prompt concern for an appendiceal tumor and an appendectomy should be considered. The different types of appendiceal tumors and cancers can be distinguished by the appearance of the cells under the microscope and by staining them for specific markers. Goblet cell carcinoid tumors tend to be easier to identify because of the unique combination of neuroendocrine and epithelial cells. | 95 | Appendiceal Cancer and Tumors |
nord_95_6 | Therapies of Appendiceal Cancer and Tumors | Once the diagnosis is established, a staging work-up including imaging studies (most commonly a CT scan of the chest, abdomen and pelvis) and tumor marker blood tests (CEA, CA 19-9 and CA 125) should be performed. (Tumor markers are proteins made by the cancer cells that can be measured in the blood.) Treatment recommendations depend on both the histology (the microscopic structure of the tumor cells) of the cancer cells and whether or not it is localized or disseminated. Most of the larger and more recent studies recommend surgical removal of the right side of the colon (right hemicolectomy) for moderately-, poorly-differentiated and SRC appendiceal cancers to ensure that all the disease has been removed and to test the regional lymph nodes for any cancer cells. There is some debate about the utility of right hemicolectomy for well-differentiated appendiceal cancers as the risk of spread to regional lymph nodes is low (<5%). LAMN do not require a right hemicolectomy as they do not spread to regional lymph nodes.For LAMN that have not spread in the abdomen, an appendectomy is all that is required. For adenocarcinomas that have not spread to the abdomen, surgery to remove the right side of the colon where the appendix originates is recommended to determine if there has been any spread of cancer cells to the local lymph nodes. For tumors and cancers that have spread away from the appendix and into the abdominal cavity or into the local lymph nodes, either intravenous chemotherapy and/or additional surgery to remove the cancer, and often heated chemotherapy delivered directly into the abdomen (HIPEC) should be considered.The role of right hemicolectomy in HAMN is still being determined.For moderately-, poorly-differentiated and SRC appendiceal cancers that have spread to regional lymph nodes or other organs outside the abdominal cavity, the usual recommendation is for systemic (intravenous) chemotherapy. 5-flourouracil-based chemotherapy regimens (the same that are used to treat colon cancer) are typically recommended. If the cancer has spread in the abdominal cavity, cytoreductive surgery to remove the cancer and abdominal perfusion with hyperthermic (heated) chemotherapy (a procedure known as HIPEC) to prevent cancer recurrence should be considered as part of the treatment regimen along with systemic chemotherapy. This should be performed at an experienced HIPEC center. For LAMN and well-differentiated appendiceal cancers that have spread to the abdominal cavity, the usual recommendation is cytoreductive surgery and HIPEC. Surveillance for cancer recurrence should include a history and physical exam, imaging studies of the chest, abdomen and pelvis and tumor markers (CEA, CA 19-9 and CA 125) every 6 months for the first two years and then yearly for at least 3 more years, with consideration of continued follow-up thereafter. | Therapies of Appendiceal Cancer and Tumors. Once the diagnosis is established, a staging work-up including imaging studies (most commonly a CT scan of the chest, abdomen and pelvis) and tumor marker blood tests (CEA, CA 19-9 and CA 125) should be performed. (Tumor markers are proteins made by the cancer cells that can be measured in the blood.) Treatment recommendations depend on both the histology (the microscopic structure of the tumor cells) of the cancer cells and whether or not it is localized or disseminated. Most of the larger and more recent studies recommend surgical removal of the right side of the colon (right hemicolectomy) for moderately-, poorly-differentiated and SRC appendiceal cancers to ensure that all the disease has been removed and to test the regional lymph nodes for any cancer cells. There is some debate about the utility of right hemicolectomy for well-differentiated appendiceal cancers as the risk of spread to regional lymph nodes is low (<5%). LAMN do not require a right hemicolectomy as they do not spread to regional lymph nodes.For LAMN that have not spread in the abdomen, an appendectomy is all that is required. For adenocarcinomas that have not spread to the abdomen, surgery to remove the right side of the colon where the appendix originates is recommended to determine if there has been any spread of cancer cells to the local lymph nodes. For tumors and cancers that have spread away from the appendix and into the abdominal cavity or into the local lymph nodes, either intravenous chemotherapy and/or additional surgery to remove the cancer, and often heated chemotherapy delivered directly into the abdomen (HIPEC) should be considered.The role of right hemicolectomy in HAMN is still being determined.For moderately-, poorly-differentiated and SRC appendiceal cancers that have spread to regional lymph nodes or other organs outside the abdominal cavity, the usual recommendation is for systemic (intravenous) chemotherapy. 5-flourouracil-based chemotherapy regimens (the same that are used to treat colon cancer) are typically recommended. If the cancer has spread in the abdominal cavity, cytoreductive surgery to remove the cancer and abdominal perfusion with hyperthermic (heated) chemotherapy (a procedure known as HIPEC) to prevent cancer recurrence should be considered as part of the treatment regimen along with systemic chemotherapy. This should be performed at an experienced HIPEC center. For LAMN and well-differentiated appendiceal cancers that have spread to the abdominal cavity, the usual recommendation is cytoreductive surgery and HIPEC. Surveillance for cancer recurrence should include a history and physical exam, imaging studies of the chest, abdomen and pelvis and tumor markers (CEA, CA 19-9 and CA 125) every 6 months for the first two years and then yearly for at least 3 more years, with consideration of continued follow-up thereafter. | 95 | Appendiceal Cancer and Tumors |
nord_96_0 | Overview of Apraxia | Apraxia is a neurological disorder characterized by the inability to perform learned (familiar) movements on command, even though the command is understood and there is a willingness to perform the movement. Both the desire and the capacity to move are present but the person simply cannot execute the act.Patients with apraxia cannot use tools or perform such acts as tying shoelaces or button shirts etc. The requirements of daily living are difficult to meet. Patients whose ability to speak is interrupted (aphasia) but who are unaffected by apraxia are able to live a relatively normal life; those with significant apraxia are almost invariably dependent.Apraxia comes in several different forms:Limb-kinetic apraxia is the inability to make precise or exact movements with a finger, an arm or a leg. An example is the inability to use a screwdriver notwithstanding that the person affected understands what is to be done and has done it in the past.Ideomotor apraxia is the inability to carry out a command from the brain to mimic limb or head movements performed or suggested by others.Conceptual apraxia is much like ideomotor ataxia but infers a more profound malfunctioning in which the function of tools is no longer understood.Ideational apraxia is the inability to create a plan for a specific movement.Buccofacial apraxia, (sometimes called facial-oral apraxia) is the inability to coordinate and carry out facial and lip movements such as whistling, winking, coughing etc on command. This form includes verbal or speech developmental apraxia, perhaps the most common form of the disorder.Constructional apraxia affects the person's ability to draw or copy simple diagrams or to construct simple figures.Oculomotor apraxia is a condition in which patients find it difficult to move their eyes.Apraxia is believed to be caused by a lesion in the neural pathways of the brain that contain the learned patterns of movement. It is often a symptom of neurological, metabolic, or other disorders that can involve the brain. | Overview of Apraxia. Apraxia is a neurological disorder characterized by the inability to perform learned (familiar) movements on command, even though the command is understood and there is a willingness to perform the movement. Both the desire and the capacity to move are present but the person simply cannot execute the act.Patients with apraxia cannot use tools or perform such acts as tying shoelaces or button shirts etc. The requirements of daily living are difficult to meet. Patients whose ability to speak is interrupted (aphasia) but who are unaffected by apraxia are able to live a relatively normal life; those with significant apraxia are almost invariably dependent.Apraxia comes in several different forms:Limb-kinetic apraxia is the inability to make precise or exact movements with a finger, an arm or a leg. An example is the inability to use a screwdriver notwithstanding that the person affected understands what is to be done and has done it in the past.Ideomotor apraxia is the inability to carry out a command from the brain to mimic limb or head movements performed or suggested by others.Conceptual apraxia is much like ideomotor ataxia but infers a more profound malfunctioning in which the function of tools is no longer understood.Ideational apraxia is the inability to create a plan for a specific movement.Buccofacial apraxia, (sometimes called facial-oral apraxia) is the inability to coordinate and carry out facial and lip movements such as whistling, winking, coughing etc on command. This form includes verbal or speech developmental apraxia, perhaps the most common form of the disorder.Constructional apraxia affects the person's ability to draw or copy simple diagrams or to construct simple figures.Oculomotor apraxia is a condition in which patients find it difficult to move their eyes.Apraxia is believed to be caused by a lesion in the neural pathways of the brain that contain the learned patterns of movement. It is often a symptom of neurological, metabolic, or other disorders that can involve the brain. | 96 | Apraxia |
nord_96_1 | Symptoms of Apraxia | The major symptom of Apraxia is a person's inability to perform movement in the absence of any physical paralysis. Commands to move are understood, but cannot be executed. When movement is initiated, it is usually very clumsy, uncontrolled and inappropriate. In some cases, movement may occur unintentionally. Apraxia is sometimes accompanied by a person's loss of ability to comprehend or use words (Aphasia).Specific types of Apraxia are characterized by an inability to perform particular movements on command. For example, in Buccofacial Apraxia, an affected individual is unable to cough, whistle, lick one's lips, or wink when asked. In Constructional Apraxia, an individual is unable to reproduce simple patterns or copy simple drawings. | Symptoms of Apraxia. The major symptom of Apraxia is a person's inability to perform movement in the absence of any physical paralysis. Commands to move are understood, but cannot be executed. When movement is initiated, it is usually very clumsy, uncontrolled and inappropriate. In some cases, movement may occur unintentionally. Apraxia is sometimes accompanied by a person's loss of ability to comprehend or use words (Aphasia).Specific types of Apraxia are characterized by an inability to perform particular movements on command. For example, in Buccofacial Apraxia, an affected individual is unable to cough, whistle, lick one's lips, or wink when asked. In Constructional Apraxia, an individual is unable to reproduce simple patterns or copy simple drawings. | 96 | Apraxia |
nord_96_2 | Causes of Apraxia | Apraxia is caused by a defect in the brain pathways that contain memory of learned patterns of movement. The lesion may be the result of certain metabolic, neurological or other disorders that involve the brain, particularly the frontal lobe (inferior parietal lobule) of the left hemisphere of the brain. In this region, complex, 3-dimensional representations of previously learned patterns and movements are stored. Patients with apraxia cannot retrieve these models of stored skilled movements.Oculomotor apraxia is a dominant genetic trait. The gene for this condition has been mapped to chromosome 2p13. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 2p13” refers to band 13 on the short arm of chromosome 2. The numbered bands specify the location of the thousands of genes that are present on each chromosome. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.Tissue or cellular damage (lesions) to other specific parts of the brain, whether as a result of stroke or wounds, tumors, or dementias, may also cause apraxia. These other locations include the so-called supplementary motor area (premotor cortex) or corpus callosum.If apraxia is the result of a stroke it usually abates within weeks. Some cases of apraxia are congenital. When a child is born with apraxia it is usually the result of malformations of the central nervous system. At the other extreme, individuals with deteriorating intellectual functioning (degenerative dementia) may also develop apraxia.Individuals with a condition of deteriorating intellectual functioning (degenerative dementia) may also develop Apraxia. | Causes of Apraxia. Apraxia is caused by a defect in the brain pathways that contain memory of learned patterns of movement. The lesion may be the result of certain metabolic, neurological or other disorders that involve the brain, particularly the frontal lobe (inferior parietal lobule) of the left hemisphere of the brain. In this region, complex, 3-dimensional representations of previously learned patterns and movements are stored. Patients with apraxia cannot retrieve these models of stored skilled movements.Oculomotor apraxia is a dominant genetic trait. The gene for this condition has been mapped to chromosome 2p13. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 2p13” refers to band 13 on the short arm of chromosome 2. The numbered bands specify the location of the thousands of genes that are present on each chromosome. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.Tissue or cellular damage (lesions) to other specific parts of the brain, whether as a result of stroke or wounds, tumors, or dementias, may also cause apraxia. These other locations include the so-called supplementary motor area (premotor cortex) or corpus callosum.If apraxia is the result of a stroke it usually abates within weeks. Some cases of apraxia are congenital. When a child is born with apraxia it is usually the result of malformations of the central nervous system. At the other extreme, individuals with deteriorating intellectual functioning (degenerative dementia) may also develop apraxia.Individuals with a condition of deteriorating intellectual functioning (degenerative dementia) may also develop Apraxia. | 96 | Apraxia |
nord_96_3 | Affects of Apraxia | There is little data available on the incidence of apraxia. Since apraxia may accompany dementia or stroke, it is more frequently diagnosed among older persons. | Affects of Apraxia. There is little data available on the incidence of apraxia. Since apraxia may accompany dementia or stroke, it is more frequently diagnosed among older persons. | 96 | Apraxia |
nord_96_4 | Related disorders of Apraxia | The following disorder may be associated with Apraxia as a secondary characteristic. It is not necessary for a differential diagnosis:Aphasia is a disturbance in the ability to comprehend or use language. It usually occurs as a result of injury to the language centers of the brain (cerebral cortex). Affected individuals may select the wrong words in conversing and may have problems interpreting verbal messages. Children born with Aphasia may not talk at all. A speech therapist may assess the quality and extent of the Aphasia, and help to educate those people who most commonly interact with the affected individual in methods to help communication. | Related disorders of Apraxia. The following disorder may be associated with Apraxia as a secondary characteristic. It is not necessary for a differential diagnosis:Aphasia is a disturbance in the ability to comprehend or use language. It usually occurs as a result of injury to the language centers of the brain (cerebral cortex). Affected individuals may select the wrong words in conversing and may have problems interpreting verbal messages. Children born with Aphasia may not talk at all. A speech therapist may assess the quality and extent of the Aphasia, and help to educate those people who most commonly interact with the affected individual in methods to help communication. | 96 | Apraxia |
nord_96_5 | Diagnosis of Apraxia | Diagnosis of Apraxia. | 96 | Apraxia |
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nord_96_6 | Therapies of Apraxia | When Apraxia is a symptom of an underlying disorder, that disease or condition must be treated. Physical and occupational therapy may be of benefit to stroke and head injured patients. When Apraxia is a symptom of another neurological disorder, the underlying condition must be treated. In some cases, children with apraxia may learn to compensate for deficits as they grow older with the help of special education and physical therapy programs.Speech therapy and special education may be particularly helpful in treating patients with developmental apraxia of speech. | Therapies of Apraxia. When Apraxia is a symptom of an underlying disorder, that disease or condition must be treated. Physical and occupational therapy may be of benefit to stroke and head injured patients. When Apraxia is a symptom of another neurological disorder, the underlying condition must be treated. In some cases, children with apraxia may learn to compensate for deficits as they grow older with the help of special education and physical therapy programs.Speech therapy and special education may be particularly helpful in treating patients with developmental apraxia of speech. | 96 | Apraxia |
nord_97_0 | Overview of Arachnoid Cysts | Arachnoid cysts are fluid-filled sacs that occur on the arachnoid membrane that covers the brain (intracranial) and the spinal cord (spinal). There are three membranes covering these parts of the central nervous system: the dura mater, arachnoid, and pia mater. Arachnoid cysts appear on the arachnoid membrane, and they may also expand into the space between the pia mater and arachnoid membranes (subarachnoid space). The most common locations for intracranial arachnoid cysts are the middle fossa (near the temporal lobe), the suprasellar region (near the third ventricle) and the posterior fossa, which contains the cerebellum, pons, and medulla oblongata.In many cases, arachnoid cysts do not cause symptoms (asymptomatic). In cases in which symptoms occur, headaches, seizures and abnormal accumulation of excessive cerebrospinal fluid in the brain (hydrocephalus) are common. The exact cause of arachnoid cysts is unknown. Arachnoid cysts are classified according to their specific location. | Overview of Arachnoid Cysts. Arachnoid cysts are fluid-filled sacs that occur on the arachnoid membrane that covers the brain (intracranial) and the spinal cord (spinal). There are three membranes covering these parts of the central nervous system: the dura mater, arachnoid, and pia mater. Arachnoid cysts appear on the arachnoid membrane, and they may also expand into the space between the pia mater and arachnoid membranes (subarachnoid space). The most common locations for intracranial arachnoid cysts are the middle fossa (near the temporal lobe), the suprasellar region (near the third ventricle) and the posterior fossa, which contains the cerebellum, pons, and medulla oblongata.In many cases, arachnoid cysts do not cause symptoms (asymptomatic). In cases in which symptoms occur, headaches, seizures and abnormal accumulation of excessive cerebrospinal fluid in the brain (hydrocephalus) are common. The exact cause of arachnoid cysts is unknown. Arachnoid cysts are classified according to their specific location. | 97 | Arachnoid Cysts |
nord_97_1 | Symptoms of Arachnoid Cysts | In most cases, arachnoid cysts are present at birth (congenital), but usually do not cause any symptoms (asymptomatic) throughout an individual's life. Less often, arachnoid cysts may develop because of head injury, the presence of a tumor, infection or surgery on the brainWhether symptoms develop depends upon the size and the specific location of the cyst within the brain. Small cysts usually do not cause symptoms. However, cysts can increase in size causing symptoms to appear, especially if they press against a cranial nerve, the brain, or the spinal cord.Most cases of arachnoid cysts that are associated with symptoms occur in childhood. The specific symptoms present vary from case to case. It is important to note that affected individuals will not have all of the symptoms listed below.The most common symptoms associated with arachnoid cysts are usually nonspecific and include headaches, nausea, vomiting, dizziness and the accumulation of excessive cerebrospinal fluid in the brain (hydrocephalus), resulting in increased intracranial pressure In rare cases, in some children, an arachnoid cyst can cause malformation of certain cranial bones, resulting in an abnormally enlarged head (macrocephaly). .A variety of additional symptoms occur in some individuals with arachnoid cysts depending upon the size and location of the cyst. Most cysts occur near the middle fossa region of the brain. Such symptoms include lethargy, seizures, vision abnormalities and hearing abnormalities. Neurological signs may be present because arachnoid cysts may cause increased pressure on structures of the brain. Such neurological findings may include developmental delays, behavioral changes, an inability to control voluntary movements (ataxia), difficulties with balance and walking and cognitive impairment. Weakness or paralysis on one side of the body (hemiparesis) has also been reported.In addition to hydrocephalus, cysts located in the suprasellar region may be associated with vision disturbances, continuous bobbing of the head, and abnormalities affecting certain hormone-producing glands that help to regulate the rate of growth, sexual development, and certain metabolic functions (endocrine system).Although they occur much less often than those found within the skull (intracranial), arachnoid cysts may also arise near the spine (spinal arachnoid cysts). Spinal arachnoid cysts may be associated with progressive weakness of the legs, tingling or numbness in the hands or feet, abnormal side-to-side curvature of the spine (scoliosis), back pain, and involuntary muscle spasms (spasticity) that result in slow, stiff movements of the legs. In rare cases, these cysts may cause paralysis of the legs (paraplegia). Urinary tract infections may also occur in individuals with spinal arachnoid cysts.Other symptoms and physical findings have been reported to be associated with arachnoid cysts including migraine headaches, attention-deficit disorder and difficulties understanding or expressing language (aphasia). The exact cause and effect relationship between these findings and arachnoid cysts is not clear. | Symptoms of Arachnoid Cysts. In most cases, arachnoid cysts are present at birth (congenital), but usually do not cause any symptoms (asymptomatic) throughout an individual's life. Less often, arachnoid cysts may develop because of head injury, the presence of a tumor, infection or surgery on the brainWhether symptoms develop depends upon the size and the specific location of the cyst within the brain. Small cysts usually do not cause symptoms. However, cysts can increase in size causing symptoms to appear, especially if they press against a cranial nerve, the brain, or the spinal cord.Most cases of arachnoid cysts that are associated with symptoms occur in childhood. The specific symptoms present vary from case to case. It is important to note that affected individuals will not have all of the symptoms listed below.The most common symptoms associated with arachnoid cysts are usually nonspecific and include headaches, nausea, vomiting, dizziness and the accumulation of excessive cerebrospinal fluid in the brain (hydrocephalus), resulting in increased intracranial pressure In rare cases, in some children, an arachnoid cyst can cause malformation of certain cranial bones, resulting in an abnormally enlarged head (macrocephaly). .A variety of additional symptoms occur in some individuals with arachnoid cysts depending upon the size and location of the cyst. Most cysts occur near the middle fossa region of the brain. Such symptoms include lethargy, seizures, vision abnormalities and hearing abnormalities. Neurological signs may be present because arachnoid cysts may cause increased pressure on structures of the brain. Such neurological findings may include developmental delays, behavioral changes, an inability to control voluntary movements (ataxia), difficulties with balance and walking and cognitive impairment. Weakness or paralysis on one side of the body (hemiparesis) has also been reported.In addition to hydrocephalus, cysts located in the suprasellar region may be associated with vision disturbances, continuous bobbing of the head, and abnormalities affecting certain hormone-producing glands that help to regulate the rate of growth, sexual development, and certain metabolic functions (endocrine system).Although they occur much less often than those found within the skull (intracranial), arachnoid cysts may also arise near the spine (spinal arachnoid cysts). Spinal arachnoid cysts may be associated with progressive weakness of the legs, tingling or numbness in the hands or feet, abnormal side-to-side curvature of the spine (scoliosis), back pain, and involuntary muscle spasms (spasticity) that result in slow, stiff movements of the legs. In rare cases, these cysts may cause paralysis of the legs (paraplegia). Urinary tract infections may also occur in individuals with spinal arachnoid cysts.Other symptoms and physical findings have been reported to be associated with arachnoid cysts including migraine headaches, attention-deficit disorder and difficulties understanding or expressing language (aphasia). The exact cause and effect relationship between these findings and arachnoid cysts is not clear. | 97 | Arachnoid Cysts |
nord_97_2 | Causes of Arachnoid Cysts | The exact cause of arachnoid cysts is not known. Researchers believe that most cases of arachnoid cysts are developmental malformations that arise from the unexplained splitting or tearing of the arachnoid membrane. According to the medical literature, cases of arachnoid cysts have run in families (familial cases) suggesting that a genetic predisposition may play a role in the development of arachnoid cysts in some individuals.In some cases, arachnoid cysts occurring in the middle fossa are accompanied by underdevelopment (hypoplasia) or compression of the temporal lobe. The exact role that temporal lobe abnormalities play in the development of middle fossa arachnoid cysts is unknown.Some complications of arachnoid cysts can occur when a cyst is damaged because of minor head trauma. Trauma can cause the fluid within a cyst to leak into other areas (e.g., subarachnoid space). Blood vessels on the surface of a cyst may tear and bleed into the cyst (intracystic hemorrhage), increasing its size. If a blood vessel bleeds on the outside of a cyst, a collection of blood (hematoma) may result. In the cases of intracystic hemorrhage and hematoma, the individual may have symptoms of increased pressure within the cranium and signs of compression of nearby nerve (neural) tissue.Arachnoid cysts can also occur secondary to other disorders such as Marfan's syndrome, arachnoiditis, or agenesis of the corpus callosum. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database). | Causes of Arachnoid Cysts. The exact cause of arachnoid cysts is not known. Researchers believe that most cases of arachnoid cysts are developmental malformations that arise from the unexplained splitting or tearing of the arachnoid membrane. According to the medical literature, cases of arachnoid cysts have run in families (familial cases) suggesting that a genetic predisposition may play a role in the development of arachnoid cysts in some individuals.In some cases, arachnoid cysts occurring in the middle fossa are accompanied by underdevelopment (hypoplasia) or compression of the temporal lobe. The exact role that temporal lobe abnormalities play in the development of middle fossa arachnoid cysts is unknown.Some complications of arachnoid cysts can occur when a cyst is damaged because of minor head trauma. Trauma can cause the fluid within a cyst to leak into other areas (e.g., subarachnoid space). Blood vessels on the surface of a cyst may tear and bleed into the cyst (intracystic hemorrhage), increasing its size. If a blood vessel bleeds on the outside of a cyst, a collection of blood (hematoma) may result. In the cases of intracystic hemorrhage and hematoma, the individual may have symptoms of increased pressure within the cranium and signs of compression of nearby nerve (neural) tissue.Arachnoid cysts can also occur secondary to other disorders such as Marfan's syndrome, arachnoiditis, or agenesis of the corpus callosum. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database). | 97 | Arachnoid Cysts |
nord_97_3 | Affects of Arachnoid Cysts | Arachnoid cysts affect males more often than females. These cysts may occur at any age and have been found in all races and geographic locations. They are the most common type of intracranial cyst. Because many cases of arachnoid cysts have no symptoms, it is difficult to determine the true frequency of this disorder in the general population. | Affects of Arachnoid Cysts. Arachnoid cysts affect males more often than females. These cysts may occur at any age and have been found in all races and geographic locations. They are the most common type of intracranial cyst. Because many cases of arachnoid cysts have no symptoms, it is difficult to determine the true frequency of this disorder in the general population. | 97 | Arachnoid Cysts |
nord_97_4 | Related disorders of Arachnoid Cysts | Symptoms of the following disorders can be similar to those of arachnoid cysts. Comparisons may be useful for a differential diagnosis:Brain tumors are growths in the brain that can be either cancerous (malignant) or noncancerous (benign). The symptoms of malignant and benign brain tumors are similar, and depend on the type of tumor and its location. Symptoms may include recurrent headache, seizures, emotional instability, nausea, and/or facial pain or numbness. There are many different types of brain tumors. (For more information on these disorders, choose “Brain Tumor” as your search term in the Rare Disease Database).Dandy-Walker malformation is a rare malformation of the brain that is present at birth (congenital). It is characterized by an abnormally enlarged space at the back of the brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts of the brain (foramina of Magendia and Luschka). Excessive amounts of fluid accumulate around the brain and cause abnormally high pressure within the skull, swelling of the head (congenital hydrocephalus), and neurological impairment. Motor delays and learning problems may also occur. Dandy-Walker malformation is a form of “obstructive” or “internal noncommunicating hydrocephalus”, meaning that the normal flow of cerebrospinal fluid is blocked resulting in the widening of the ventricles. (For more information on this disorder, choose “Dandy-Walker” as your search term in the Rare Disease Database).Empty sella syndrome is a rare disorder characterized by enlargement or malformation of a structure in the head known as the sella turcica. The sella turcica is a saddle-shaped depression located in the bone at the base of skull (sphenoid bone), in which resides the pituitary gland. In empty sella syndrome, the malformed sella turcica is often either partially or completely filled with cerebrospinal fluid. As a result, the pituitary gland is often compressed and flattened so that the sella turcica appears empty. Most individuals with empty sella syndrome do not have any associated symptoms. Occasionally, headaches or pituitary dysfunction may occur. Empty sella syndrome may occur as a primary disorder, for which the cause is unknown (idiopathic), or as a secondary disorder, in which it occurs due to an underlying condition or disorder such as a pituitary tumor or trauma in the pituitary region. (For more information on this disorder, choose “Empty Sella” as your search term in the Rare Disease Database).Porencephaly is a general term for certain disorders that affect the central nervous system. Porencephaly may be classified as sporadic or familial. Sporadic porencephaly can have many different causes including infection just before or just after birth (perinatal infection), trauma, maternal disease or sickness, maternal diabetes, or maternal use of alcohol or drugs such as cocaine during pregnancy. Autosomal dominant porencephaly type I occurs due to mutations of the COL4A1 gene. In porencephaly, cysts or cavities form on the surface of the brain. These cysts or cavities may become filled with cerebrospinal fluid, a colorless fluid that normally surrounds the brain and spinal cord to provide protection and nourishment. The severity and associated symptoms of porencephaly vary dramatically from one person to another based upon the size and exact locations of the fluid-filled cavities or cysts. Some infants develop serious complications shortly after birth; others individuals may have mild symptoms that may go undetected. The signs and symptoms of porencephaly may include weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, varying degrees of cognitive impairment, and migraines. Individuals with autosomal dominant porencephaly type I are predisposed to damage to small blood vessels, including the small vessels within the brain. (For more information on this disorder, choose “porencephaly” as your search term in the Rare Disease Database). | Related disorders of Arachnoid Cysts. Symptoms of the following disorders can be similar to those of arachnoid cysts. Comparisons may be useful for a differential diagnosis:Brain tumors are growths in the brain that can be either cancerous (malignant) or noncancerous (benign). The symptoms of malignant and benign brain tumors are similar, and depend on the type of tumor and its location. Symptoms may include recurrent headache, seizures, emotional instability, nausea, and/or facial pain or numbness. There are many different types of brain tumors. (For more information on these disorders, choose “Brain Tumor” as your search term in the Rare Disease Database).Dandy-Walker malformation is a rare malformation of the brain that is present at birth (congenital). It is characterized by an abnormally enlarged space at the back of the brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts of the brain (foramina of Magendia and Luschka). Excessive amounts of fluid accumulate around the brain and cause abnormally high pressure within the skull, swelling of the head (congenital hydrocephalus), and neurological impairment. Motor delays and learning problems may also occur. Dandy-Walker malformation is a form of “obstructive” or “internal noncommunicating hydrocephalus”, meaning that the normal flow of cerebrospinal fluid is blocked resulting in the widening of the ventricles. (For more information on this disorder, choose “Dandy-Walker” as your search term in the Rare Disease Database).Empty sella syndrome is a rare disorder characterized by enlargement or malformation of a structure in the head known as the sella turcica. The sella turcica is a saddle-shaped depression located in the bone at the base of skull (sphenoid bone), in which resides the pituitary gland. In empty sella syndrome, the malformed sella turcica is often either partially or completely filled with cerebrospinal fluid. As a result, the pituitary gland is often compressed and flattened so that the sella turcica appears empty. Most individuals with empty sella syndrome do not have any associated symptoms. Occasionally, headaches or pituitary dysfunction may occur. Empty sella syndrome may occur as a primary disorder, for which the cause is unknown (idiopathic), or as a secondary disorder, in which it occurs due to an underlying condition or disorder such as a pituitary tumor or trauma in the pituitary region. (For more information on this disorder, choose “Empty Sella” as your search term in the Rare Disease Database).Porencephaly is a general term for certain disorders that affect the central nervous system. Porencephaly may be classified as sporadic or familial. Sporadic porencephaly can have many different causes including infection just before or just after birth (perinatal infection), trauma, maternal disease or sickness, maternal diabetes, or maternal use of alcohol or drugs such as cocaine during pregnancy. Autosomal dominant porencephaly type I occurs due to mutations of the COL4A1 gene. In porencephaly, cysts or cavities form on the surface of the brain. These cysts or cavities may become filled with cerebrospinal fluid, a colorless fluid that normally surrounds the brain and spinal cord to provide protection and nourishment. The severity and associated symptoms of porencephaly vary dramatically from one person to another based upon the size and exact locations of the fluid-filled cavities or cysts. Some infants develop serious complications shortly after birth; others individuals may have mild symptoms that may go undetected. The signs and symptoms of porencephaly may include weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, varying degrees of cognitive impairment, and migraines. Individuals with autosomal dominant porencephaly type I are predisposed to damage to small blood vessels, including the small vessels within the brain. (For more information on this disorder, choose “porencephaly” as your search term in the Rare Disease Database). | 97 | Arachnoid Cysts |
nord_97_5 | Diagnosis of Arachnoid Cysts | A diagnosis of arachnoid cysts is often made incidentally, often during examination of an individual with seizures. A diagnosis may be suspected based upon a detailed patient history, a thorough clinical examination, and a variety of specialized tests, especially advanced imaging studies such as computed tomography (CT scan) and magnetic resonance imaging (MRI). CT scans and MRIs can reveal or confirm the presence of arachnoid cysts. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the brain. | Diagnosis of Arachnoid Cysts. A diagnosis of arachnoid cysts is often made incidentally, often during examination of an individual with seizures. A diagnosis may be suspected based upon a detailed patient history, a thorough clinical examination, and a variety of specialized tests, especially advanced imaging studies such as computed tomography (CT scan) and magnetic resonance imaging (MRI). CT scans and MRIs can reveal or confirm the presence of arachnoid cysts. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the brain. | 97 | Arachnoid Cysts |
nord_97_6 | Therapies of Arachnoid Cysts | Treatment
Most arachnoid cysts are found incidentally and remain constant in size, leading many physicians to recommend conservative treatment. When no symptoms are present, no treatment may be necessary and affected individuals may be periodically monitored. If symptoms arise, a cyst can be reevaluated.When treatment is necessary the specific therapy used depends upon whether symptoms are present, the size of the cyst and the specific location of the cyst within the skull.In cases where treatment is recommended, therapy traditionally consists of one of two procedures – an open craniotomy fenestration or ventriculoperitoneal shunting.During a craniotomy fenestration, a portion of the skull is removed to give a surgeon access to the cyst, where multiple openings are made in the cyst wall, (fenestrations), to allow cerebrospinal fluid to drain into the subarachnoid space where the fluid is reabsorbed into the surrounding tissue. Alternatively, some cases may be treated by surgically inserting a device (shunt) into the cyst to provide drainage either into the ventricular system of the brain or into the abdominal cavity. This will drain the cyst and provide an adequate passageway for cerebrospinal fluid to circulate.More recently, advancements in minimally invasive brain and skull base surgery have evolved these traditional procedures into fully endoscopic techniques, distinguished by shorter operating times, fewer complications, excellent outcomes with faster recovery and overall decreased patient morbidity. While the approach varies depending on the size and location of the arachnoid cyst, fully endoscopic surgical management has provided the surgeon with superior access for either fenestration, or in other cases, resection of the cyst without the complications and risks associated with brain manipulation or retraction. Few facilities provide minimally invasive, endoscope assisted fenestrations, endoscopic shunt placement and endscope assisted or fully endoscopic resection of arachnoid cysts as treatment when indicated.Spinal arachnoid cysts may be treated by the complete surgical removal (resection) of the cyst, if possible. Surgery generally leads to a resolution of symptoms. In some cases, complete surgical removal of a spinal cyst is not possible. In such cases, fenestration or shunting of the cyst to drain the fluid may be necessary.Other treatment is symptomatic and supportive. | Therapies of Arachnoid Cysts. Treatment
Most arachnoid cysts are found incidentally and remain constant in size, leading many physicians to recommend conservative treatment. When no symptoms are present, no treatment may be necessary and affected individuals may be periodically monitored. If symptoms arise, a cyst can be reevaluated.When treatment is necessary the specific therapy used depends upon whether symptoms are present, the size of the cyst and the specific location of the cyst within the skull.In cases where treatment is recommended, therapy traditionally consists of one of two procedures – an open craniotomy fenestration or ventriculoperitoneal shunting.During a craniotomy fenestration, a portion of the skull is removed to give a surgeon access to the cyst, where multiple openings are made in the cyst wall, (fenestrations), to allow cerebrospinal fluid to drain into the subarachnoid space where the fluid is reabsorbed into the surrounding tissue. Alternatively, some cases may be treated by surgically inserting a device (shunt) into the cyst to provide drainage either into the ventricular system of the brain or into the abdominal cavity. This will drain the cyst and provide an adequate passageway for cerebrospinal fluid to circulate.More recently, advancements in minimally invasive brain and skull base surgery have evolved these traditional procedures into fully endoscopic techniques, distinguished by shorter operating times, fewer complications, excellent outcomes with faster recovery and overall decreased patient morbidity. While the approach varies depending on the size and location of the arachnoid cyst, fully endoscopic surgical management has provided the surgeon with superior access for either fenestration, or in other cases, resection of the cyst without the complications and risks associated with brain manipulation or retraction. Few facilities provide minimally invasive, endoscope assisted fenestrations, endoscopic shunt placement and endscope assisted or fully endoscopic resection of arachnoid cysts as treatment when indicated.Spinal arachnoid cysts may be treated by the complete surgical removal (resection) of the cyst, if possible. Surgery generally leads to a resolution of symptoms. In some cases, complete surgical removal of a spinal cyst is not possible. In such cases, fenestration or shunting of the cyst to drain the fluid may be necessary.Other treatment is symptomatic and supportive. | 97 | Arachnoid Cysts |
nord_98_0 | Overview of Arginase-1 Deficiency | Summary
Arginase-1 deficiency is a rare inherited disorder characterized by complete or partial lack of the enzyme arginase in the liver and red blood cells. Arginase is one of six enzymes that play a role in the breakdown and removal of nitrogen from the body, a process known as the urea cycle. The lack of the arginase enzyme results in excessive accumulation of nitrogen, in the form of ammonia (hyperammonemia), in the blood and arginine (hyperarginemia) in the blood and cerebrospinal fluid. Untreated children may exhibit seizures, progressive spasticity, short stature and intellectual disability. Most affected infants can now be identified at birth through newborn screening. Arginase-1 deficiency is inherited as an autosomal recessive genetic disorder.Introduction
The urea cycle disorders are a group of rare disorders affecting the urea cycle, a series of biochemical processes in which nitrogen is converted into urea and removed from the body through the urine. Nitrogen is a waste product of protein metabolism. Failure to break down nitrogen results in the abnormal accumulation of nitrogen, in the form of ammonia, in the blood. In arginase-1 deficiency the accumulation of arginine in the body and not excess ammonia is the predominant biochemical and pathological abnormality. | Overview of Arginase-1 Deficiency. Summary
Arginase-1 deficiency is a rare inherited disorder characterized by complete or partial lack of the enzyme arginase in the liver and red blood cells. Arginase is one of six enzymes that play a role in the breakdown and removal of nitrogen from the body, a process known as the urea cycle. The lack of the arginase enzyme results in excessive accumulation of nitrogen, in the form of ammonia (hyperammonemia), in the blood and arginine (hyperarginemia) in the blood and cerebrospinal fluid. Untreated children may exhibit seizures, progressive spasticity, short stature and intellectual disability. Most affected infants can now be identified at birth through newborn screening. Arginase-1 deficiency is inherited as an autosomal recessive genetic disorder.Introduction
The urea cycle disorders are a group of rare disorders affecting the urea cycle, a series of biochemical processes in which nitrogen is converted into urea and removed from the body through the urine. Nitrogen is a waste product of protein metabolism. Failure to break down nitrogen results in the abnormal accumulation of nitrogen, in the form of ammonia, in the blood. In arginase-1 deficiency the accumulation of arginine in the body and not excess ammonia is the predominant biochemical and pathological abnormality. | 98 | Arginase-1 Deficiency |
nord_98_1 | Symptoms of Arginase-1 Deficiency | Symptoms associated with arginase-1 deficiency differ from those associated with other disorders of the urea cycle. Most infants with arginase-1 deficiency do not exhibit any symptoms during the first few months to a year of life. Infants with arginase-1 deficiency infrequently experience severe hyperammonemia or hyperammonemic coma, which are characteristic of the other urea cycle disorders.Affected children may experience a lag in growth between one and three years and may walk on their toes and develop progressive stiffness and lack of control of voluntary movements of the legs (spastic diplegia). Cognitive development slows or stops and if untreated, children develop severe spasticity, an inability to walk, loss of bowel and bladder control and severe intellectual disability.Almost all affected children have growth deficiency and many also experience seizures. | Symptoms of Arginase-1 Deficiency. Symptoms associated with arginase-1 deficiency differ from those associated with other disorders of the urea cycle. Most infants with arginase-1 deficiency do not exhibit any symptoms during the first few months to a year of life. Infants with arginase-1 deficiency infrequently experience severe hyperammonemia or hyperammonemic coma, which are characteristic of the other urea cycle disorders.Affected children may experience a lag in growth between one and three years and may walk on their toes and develop progressive stiffness and lack of control of voluntary movements of the legs (spastic diplegia). Cognitive development slows or stops and if untreated, children develop severe spasticity, an inability to walk, loss of bowel and bladder control and severe intellectual disability.Almost all affected children have growth deficiency and many also experience seizures. | 98 | Arginase-1 Deficiency |
nord_98_2 | Causes of Arginase-1 Deficiency | Arginase-1 deficiency is inherited as an autosomal recessive genetic disorder and is caused by changes (mutations or pathogenic variants) in the ARG1 gene. Mutations in the ARG1 gene result in production of an abnormal arginase enzyme.Recessive genetic disorders occur when an individual inherits two copies of an altered gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same altered gene, which increases the risk to have children with a recessive genetic disorder. | Causes of Arginase-1 Deficiency. Arginase-1 deficiency is inherited as an autosomal recessive genetic disorder and is caused by changes (mutations or pathogenic variants) in the ARG1 gene. Mutations in the ARG1 gene result in production of an abnormal arginase enzyme.Recessive genetic disorders occur when an individual inherits two copies of an altered gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same altered gene, which increases the risk to have children with a recessive genetic disorder. | 98 | Arginase-1 Deficiency |
nord_98_3 | Affects of Arginase-1 Deficiency | Arginase-1 deficiency has been estimated to occur in approximately 1 in 300,000-1,000,000 births.Arginase-1 deficiency is among the least common of all the disorders of the urea cycle. The estimated frequency of urea cycle disorders collectively is one in 30,000. However, because urea cycle disorders like arginase-1 deficiency often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency of urea cycle disorders in the general population. This is likely to change now that arginase-1 deficiency can be diagnosed by newborn screening. | Affects of Arginase-1 Deficiency. Arginase-1 deficiency has been estimated to occur in approximately 1 in 300,000-1,000,000 births.Arginase-1 deficiency is among the least common of all the disorders of the urea cycle. The estimated frequency of urea cycle disorders collectively is one in 30,000. However, because urea cycle disorders like arginase-1 deficiency often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency of urea cycle disorders in the general population. This is likely to change now that arginase-1 deficiency can be diagnosed by newborn screening. | 98 | Arginase-1 Deficiency |
nord_98_4 | Related disorders of Arginase-1 Deficiency | Symptoms of the following disorders may be similar to those of arginase-1 deficiency. Comparisons may be useful for a differential diagnosis:The urea cycle disorders are a group of rare disorders affecting the urea cycle, a series of biochemical processes in which nitrogen is converted into urea and removed from the body through the urine. Nitrogen is a waste product of protein metabolism. The symptoms of all urea cycle disorders vary in severity and result from the excessive accumulation of ammonia in the blood and body tissues (hyperammonemia). Common symptoms include lack of appetite, vomiting, drowsiness, seizures and/or coma. The liver may be abnormally enlarged (hepatomegaly). In some patients, life-threatening complications may result. In addition to arginase-1 deficiency, the other urea cycle disorders are: carbamyl phosphate synthetase (CPS) deficiency; argininosuccinate synthetase deficiency (citrullinemia); argininosuccinate lyase (ASL) deficiency; ornithine transcarbamylase (OTC) deficiency; and N-acetylglutamate synthetase (NAGS) deficiency. (For more information about these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Cerebral palsy is a neurological movement disorder characterized by a lack of muscle control and impaired ability to coordinate movement (ataxia). This disorder is usually a result of injury to the brain during early development in the uterus or at birth. Cerebral palsy is not a progressive disease. An infant with cerebral palsy may experience developmental delays during the first or second year of life. As an affected child grows, additional symptoms may develop, including drooling, speech impairment, difficulty maintaining bladder and/or bowel control, convulsive seizures, hand tremors and/or difficulty coordinating voluntary movement. Spastic cerebral palsy is characterized by involuntary contractions of the muscles in the arms and legs and an awkward “scissor” gait. These muscle movements may be accompanied by facial grimacing and/or abnormal tongue movements.Reye syndrome is a rare childhood disease characterized by liver failure, abnormal brain function (encephalopathy), abnormally low levels of glucose (hypoglycemia) and high levels of ammonia in the blood. This disorder usually follows a viral infection. It may be triggered using aspirin in children recovering from chicken pox or influenza. (For more information on this disorder, choose “Reye” as your search term in the Rare Disease Database.) | Related disorders of Arginase-1 Deficiency. Symptoms of the following disorders may be similar to those of arginase-1 deficiency. Comparisons may be useful for a differential diagnosis:The urea cycle disorders are a group of rare disorders affecting the urea cycle, a series of biochemical processes in which nitrogen is converted into urea and removed from the body through the urine. Nitrogen is a waste product of protein metabolism. The symptoms of all urea cycle disorders vary in severity and result from the excessive accumulation of ammonia in the blood and body tissues (hyperammonemia). Common symptoms include lack of appetite, vomiting, drowsiness, seizures and/or coma. The liver may be abnormally enlarged (hepatomegaly). In some patients, life-threatening complications may result. In addition to arginase-1 deficiency, the other urea cycle disorders are: carbamyl phosphate synthetase (CPS) deficiency; argininosuccinate synthetase deficiency (citrullinemia); argininosuccinate lyase (ASL) deficiency; ornithine transcarbamylase (OTC) deficiency; and N-acetylglutamate synthetase (NAGS) deficiency. (For more information about these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Cerebral palsy is a neurological movement disorder characterized by a lack of muscle control and impaired ability to coordinate movement (ataxia). This disorder is usually a result of injury to the brain during early development in the uterus or at birth. Cerebral palsy is not a progressive disease. An infant with cerebral palsy may experience developmental delays during the first or second year of life. As an affected child grows, additional symptoms may develop, including drooling, speech impairment, difficulty maintaining bladder and/or bowel control, convulsive seizures, hand tremors and/or difficulty coordinating voluntary movement. Spastic cerebral palsy is characterized by involuntary contractions of the muscles in the arms and legs and an awkward “scissor” gait. These muscle movements may be accompanied by facial grimacing and/or abnormal tongue movements.Reye syndrome is a rare childhood disease characterized by liver failure, abnormal brain function (encephalopathy), abnormally low levels of glucose (hypoglycemia) and high levels of ammonia in the blood. This disorder usually follows a viral infection. It may be triggered using aspirin in children recovering from chicken pox or influenza. (For more information on this disorder, choose “Reye” as your search term in the Rare Disease Database.) | 98 | Arginase-1 Deficiency |
nord_98_5 | Diagnosis of Arginase-1 Deficiency | Most affected infants are now identified at birth through newborn screening. Arginase enzyme activity is usually not detectable in red blood cells from affected individuals. Molecular genetic testing is available to confirm the diagnosis. If two pathogenic variants the ARG1 gene are not found, red blood cell enzyme testing is used to confirm the diagnosis. | Diagnosis of Arginase-1 Deficiency. Most affected infants are now identified at birth through newborn screening. Arginase enzyme activity is usually not detectable in red blood cells from affected individuals. Molecular genetic testing is available to confirm the diagnosis. If two pathogenic variants the ARG1 gene are not found, red blood cell enzyme testing is used to confirm the diagnosis. | 98 | Arginase-1 Deficiency |
nord_98_6 | Therapies of Arginase-1 Deficiency | Treatment
Treatment should be coordinated by a metabolic specialist and is based on reducing plasma ammonia and arginine concentration, preventing excess ammonia from being formed, and reducing the amount of nitrogen in the diet.Reduction of plasma ammonia concentration is accomplished by dialysis and several different methods are available. This should be used only when the high levels are producing severe symptoms.The nitrogen scavenger drugs sodium phenylacetate and sodium benzoate provide an alternative pathway for removing excess nitrogen. Intravenous and oral forms of these medications are available (Ammonul). Phenylbutyrate (Buphenyl) has a less offensive odor than the other medications but is available as oral therapy only. Ravicti is a form of phenylbutyrate that is less irritating to the gastrointestinal track and easier to take.Dietary restrictions in individuals with arginase-1 deficiency are aimed at limiting the amount of arginine and protein intake. Children with arginase-1 deficiency are placed on a low-protein, arginine-restricted diet supplemented by essential amino acids.
Seizures are treated with phenobarbital or carbamazepine. Valproic acid should be avoided, as it can increase blood ammonia levels.Affected individuals should receive periodic blood tests to determine the levels of ammonia and arginine in the blood and to be sure that liver function is not impaired. Excessive levels of ammonia or arginine should be promptly treated.Genetic counseling is recommended for affected individuals and their families. | Therapies of Arginase-1 Deficiency. Treatment
Treatment should be coordinated by a metabolic specialist and is based on reducing plasma ammonia and arginine concentration, preventing excess ammonia from being formed, and reducing the amount of nitrogen in the diet.Reduction of plasma ammonia concentration is accomplished by dialysis and several different methods are available. This should be used only when the high levels are producing severe symptoms.The nitrogen scavenger drugs sodium phenylacetate and sodium benzoate provide an alternative pathway for removing excess nitrogen. Intravenous and oral forms of these medications are available (Ammonul). Phenylbutyrate (Buphenyl) has a less offensive odor than the other medications but is available as oral therapy only. Ravicti is a form of phenylbutyrate that is less irritating to the gastrointestinal track and easier to take.Dietary restrictions in individuals with arginase-1 deficiency are aimed at limiting the amount of arginine and protein intake. Children with arginase-1 deficiency are placed on a low-protein, arginine-restricted diet supplemented by essential amino acids.
Seizures are treated with phenobarbital or carbamazepine. Valproic acid should be avoided, as it can increase blood ammonia levels.Affected individuals should receive periodic blood tests to determine the levels of ammonia and arginine in the blood and to be sure that liver function is not impaired. Excessive levels of ammonia or arginine should be promptly treated.Genetic counseling is recommended for affected individuals and their families. | 98 | Arginase-1 Deficiency |
nord_99_0 | Overview of Arginine: Glycine Amidinotransferase Deficiency | SummaryArginine: glycine amidinotransferase deficiency (AGAT) is one of the three cerebral creatine deficiency syndromes (CCDS). These conditions are inborn errors of creatine metabolism which interrupt the formation or transport of creatine. Creatine is necessary to use properly adenosine triphosphate (ATP), which provides energy to all cells in the body. | Overview of Arginine: Glycine Amidinotransferase Deficiency. SummaryArginine: glycine amidinotransferase deficiency (AGAT) is one of the three cerebral creatine deficiency syndromes (CCDS). These conditions are inborn errors of creatine metabolism which interrupt the formation or transport of creatine. Creatine is necessary to use properly adenosine triphosphate (ATP), which provides energy to all cells in the body. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
nord_99_1 | Symptoms of Arginine: Glycine Amidinotransferase Deficiency | The severity of AGAT varies from patient to patient. People with AGAT typically present with mild to moderate intellectual disabilities, delayed speech and may have seizure activity. Some individuals may develop autistic like behaviors. Children with AGAT may not gain weight and grow at the expected rate (failure to thrive) and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily. | Symptoms of Arginine: Glycine Amidinotransferase Deficiency. The severity of AGAT varies from patient to patient. People with AGAT typically present with mild to moderate intellectual disabilities, delayed speech and may have seizure activity. Some individuals may develop autistic like behaviors. Children with AGAT may not gain weight and grow at the expected rate (failure to thrive) and have delayed development of motor skills such as sitting and walking. Affected individuals may also have weak muscle tone and tend to tire easily. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
nord_99_2 | Causes of Arginine: Glycine Amidinotransferase Deficiency | AGAT is the first step of creatine production, resulting in the formation of guanidinoacetate, the immediate precursor of creatine. Changes (mutations or pathogenic variants) in the GATM gene impair the body’s production of creatine. Out of the three CCDS, AGAT is the least reported. Affected individuals may demonstrate cerebral creatine deficiency on MR spectroscopy and low GAA in plasma. The inheritance pattern for AGAT is autosomal recessive. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. | Causes of Arginine: Glycine Amidinotransferase Deficiency. AGAT is the first step of creatine production, resulting in the formation of guanidinoacetate, the immediate precursor of creatine. Changes (mutations or pathogenic variants) in the GATM gene impair the body’s production of creatine. Out of the three CCDS, AGAT is the least reported. Affected individuals may demonstrate cerebral creatine deficiency on MR spectroscopy and low GAA in plasma. The inheritance pattern for AGAT is autosomal recessive. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
nord_99_3 | Affects of Arginine: Glycine Amidinotransferase Deficiency | Fewer than 20 patients with AGAT have reported worldwide. | Affects of Arginine: Glycine Amidinotransferase Deficiency. Fewer than 20 patients with AGAT have reported worldwide. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
nord_99_4 | Related disorders of Arginine: Glycine Amidinotransferase Deficiency | CCDS patients are frequently misdiagnosed with cerebral palsy as infants and toddlers. Children are often misdiagnosed with autism or global developmental delays. | Related disorders of Arginine: Glycine Amidinotransferase Deficiency. CCDS patients are frequently misdiagnosed with cerebral palsy as infants and toddlers. Children are often misdiagnosed with autism or global developmental delays. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
nord_99_5 | Diagnosis of Arginine: Glycine Amidinotransferase Deficiency | Testing in plasma is recommended by measuring the concentration of creatine (Cr), and guanidinoacetate (GAA). A positive screen for AGAT is based on plasma GAA that is low with creatine being low to normal. Urine GAA is usually low but is difficult to distinguish from normal levels. Follow up genomic testing for pathogenic variants in the GATM gene may be ordered along with brain MRI with spectroscopy to confirm an AGAT diagnosis. MRI with spectroscopy is useful for measuring creatine levels in the brain.Generally not required for diagnosis, but cultured skin fibroblasts may be helpful when gene sequencing test results are unclear. | Diagnosis of Arginine: Glycine Amidinotransferase Deficiency. Testing in plasma is recommended by measuring the concentration of creatine (Cr), and guanidinoacetate (GAA). A positive screen for AGAT is based on plasma GAA that is low with creatine being low to normal. Urine GAA is usually low but is difficult to distinguish from normal levels. Follow up genomic testing for pathogenic variants in the GATM gene may be ordered along with brain MRI with spectroscopy to confirm an AGAT diagnosis. MRI with spectroscopy is useful for measuring creatine levels in the brain.Generally not required for diagnosis, but cultured skin fibroblasts may be helpful when gene sequencing test results are unclear. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
nord_99_6 | Therapies of Arginine: Glycine Amidinotransferase Deficiency | Treatment
Individual diagnosed with AGAT may require the coordinated efforts of a team of specialists. A pediatrician or an adult primary care physician, neurologist, geneticist, dietician and a doctor who is familiar with metabolic disorders may need to work together to ensure a comprehensive approach to treatment. Occupational, speech, and physical therapists may be necessary to treat developmental disabilities and behavior therapy to address behavior problems.Treatments vary with each AGAT patient. Oral creatine monohydrate is given to replenish creatine levels in the brain and other tissues in individuals with AGAT. For AGAT patients being treated with creatine monohydrate, a routine measurement of renal function should be considered to detect possible creatine-associated kidney disease (nephropathy).Prevention of Primary Symptoms
Early treatment at the first sign of symptoms in patients with AGAT is effective in improving a patient’s quality of life. The treatment in newborn siblings of individuals with AGAT deficiency can prevent disease manifestation. | Therapies of Arginine: Glycine Amidinotransferase Deficiency. Treatment
Individual diagnosed with AGAT may require the coordinated efforts of a team of specialists. A pediatrician or an adult primary care physician, neurologist, geneticist, dietician and a doctor who is familiar with metabolic disorders may need to work together to ensure a comprehensive approach to treatment. Occupational, speech, and physical therapists may be necessary to treat developmental disabilities and behavior therapy to address behavior problems.Treatments vary with each AGAT patient. Oral creatine monohydrate is given to replenish creatine levels in the brain and other tissues in individuals with AGAT. For AGAT patients being treated with creatine monohydrate, a routine measurement of renal function should be considered to detect possible creatine-associated kidney disease (nephropathy).Prevention of Primary Symptoms
Early treatment at the first sign of symptoms in patients with AGAT is effective in improving a patient’s quality of life. The treatment in newborn siblings of individuals with AGAT deficiency can prevent disease manifestation. | 99 | Arginine: Glycine Amidinotransferase Deficiency |
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