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nord_357_1 | Symptoms of Dejerine-Sottas Syndrome | DSS often begins suddenly by age two. Tingling, prickling or burning sensations are usually the first symptoms. Muscle weakness is usually first noticed in the back of the leg. This then spreads to the front leg muscles. Children may have delayed motor milestones, including walking at preschool age or later. Some individuals may need to use a wheelchair by their teenage years. The hand and forearm muscles may become weak as the condition worsens. Individuals with DSS may have respiratory insufficiency, meaning they do not take in enough oxygen or breathe out enough carbon dioxide. Mild vision difficulties may also occur. Other symptoms include pain, loss of heat sensitivity, absence of reflexes, muscle loss (atrophy) of leg muscles, scoliosis (curving of the spine), and ataxia (loss of coordination and balance). Symptoms can vary among individuals diagnosed with DSS. | Symptoms of Dejerine-Sottas Syndrome. DSS often begins suddenly by age two. Tingling, prickling or burning sensations are usually the first symptoms. Muscle weakness is usually first noticed in the back of the leg. This then spreads to the front leg muscles. Children may have delayed motor milestones, including walking at preschool age or later. Some individuals may need to use a wheelchair by their teenage years. The hand and forearm muscles may become weak as the condition worsens. Individuals with DSS may have respiratory insufficiency, meaning they do not take in enough oxygen or breathe out enough carbon dioxide. Mild vision difficulties may also occur. Other symptoms include pain, loss of heat sensitivity, absence of reflexes, muscle loss (atrophy) of leg muscles, scoliosis (curving of the spine), and ataxia (loss of coordination and balance). Symptoms can vary among individuals diagnosed with DSS. | 357 | Dejerine-Sottas Syndrome |
nord_357_2 | Causes of Dejerine-Sottas Syndrome | DSS is caused by changes (mutations) in several different genes. Genes associated with DSS include MPZ, EGR2, PMP22, and PRX. Mutations in these genes can result in the continued loss of myelin (the protective sheath surrounding nerves) leading to muscle weakness and mobility problems. Not all genes associated with DSS have been identified. For about 45% of individuals diagnosed with DSS, the genetic cause of the condition has been determined. This may indicate that other genes not yet identified could also be associated with DSS. DSS can be inherited in a dominant or recessive manner. Individuals with a dominant form of the condition may have earlier symptom onset compared to individuals with the recessive form.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 (changed) 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.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 Dejerine-Sottas Syndrome. DSS is caused by changes (mutations) in several different genes. Genes associated with DSS include MPZ, EGR2, PMP22, and PRX. Mutations in these genes can result in the continued loss of myelin (the protective sheath surrounding nerves) leading to muscle weakness and mobility problems. Not all genes associated with DSS have been identified. For about 45% of individuals diagnosed with DSS, the genetic cause of the condition has been determined. This may indicate that other genes not yet identified could also be associated with DSS. DSS can be inherited in a dominant or recessive manner. Individuals with a dominant form of the condition may have earlier symptom onset compared to individuals with the recessive form.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 (changed) 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.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. | 357 | Dejerine-Sottas Syndrome |
nord_357_3 | Affects of Dejerine-Sottas Syndrome | Dejerine-Sottas syndrome often begins by age two. This disorder is thought to affect males and females equally. It can affect people from all races and ethnicities. | Affects of Dejerine-Sottas Syndrome. Dejerine-Sottas syndrome often begins by age two. This disorder is thought to affect males and females equally. It can affect people from all races and ethnicities. | 357 | Dejerine-Sottas Syndrome |
nord_357_4 | Related disorders of Dejerine-Sottas Syndrome | Charcot-Marie-Tooth (CMT) disease is a group of disorders in which the motor and/or sensory peripheral nerves are affected, resulting in muscle weakness and atrophy as well as sensory loss. Nerves in the feet, legs, and sometimes the hands are affected. (For more information, choose “CMT” as your search term in the Rare Disease Database.)Hereditary sensory radicular neuropathy is a dominant hereditary disorder characterized initially by pain and loss of temperature sensation in the foot and lower leg. Later, attacks of sharp pain throughout the body may occur with muscle weakness and ulcers on toes. | Related disorders of Dejerine-Sottas Syndrome. Charcot-Marie-Tooth (CMT) disease is a group of disorders in which the motor and/or sensory peripheral nerves are affected, resulting in muscle weakness and atrophy as well as sensory loss. Nerves in the feet, legs, and sometimes the hands are affected. (For more information, choose “CMT” as your search term in the Rare Disease Database.)Hereditary sensory radicular neuropathy is a dominant hereditary disorder characterized initially by pain and loss of temperature sensation in the foot and lower leg. Later, attacks of sharp pain throughout the body may occur with muscle weakness and ulcers on toes. | 357 | Dejerine-Sottas Syndrome |
nord_357_5 | Diagnosis of Dejerine-Sottas Syndrome | Diagnosis of DSS can be made through genetic testing or based on symptoms and disease severity. Criteria for a clinical diagnosis include: | Diagnosis of Dejerine-Sottas Syndrome. Diagnosis of DSS can be made through genetic testing or based on symptoms and disease severity. Criteria for a clinical diagnosis include: | 357 | Dejerine-Sottas Syndrome |
nord_357_6 | Therapies of Dejerine-Sottas Syndrome | Treatment
There is no cure for DSS. Treatment is supportive and aimed at reducing symptoms. Individuals may see a team of neurologists, physiatrists, orthopedic surgeons (specialists trained in surgery of the musculoskeletal system), and physical and occupational therapists. Ankle or foot surgery or special shoes with good ankle support can help correct or stabilize joints involved with walking. Muscle pain can be treated with acetaminophen or nonsteroidal anti-inflammatory medications. Nerve pain can be treated with tricyclic antidepressants or other medications such as carbamazepine or gabapentin. It is important to work with a doctor to identify the type of pain, so the best medication can be prescribed. Certain medications should not be taken if an individual is diagnosed with DSS.Some organizations offer assistance to individuals with vision or mobility difficulties and their families. Genetic counseling may be helpful for families and individuals diagnosed with DSS. | Therapies of Dejerine-Sottas Syndrome. Treatment
There is no cure for DSS. Treatment is supportive and aimed at reducing symptoms. Individuals may see a team of neurologists, physiatrists, orthopedic surgeons (specialists trained in surgery of the musculoskeletal system), and physical and occupational therapists. Ankle or foot surgery or special shoes with good ankle support can help correct or stabilize joints involved with walking. Muscle pain can be treated with acetaminophen or nonsteroidal anti-inflammatory medications. Nerve pain can be treated with tricyclic antidepressants or other medications such as carbamazepine or gabapentin. It is important to work with a doctor to identify the type of pain, so the best medication can be prescribed. Certain medications should not be taken if an individual is diagnosed with DSS.Some organizations offer assistance to individuals with vision or mobility difficulties and their families. Genetic counseling may be helpful for families and individuals diagnosed with DSS. | 357 | Dejerine-Sottas Syndrome |
nord_358_0 | Overview of Dengue Fever | SummaryDengue fever is a virus transmitted by the bite of a female Aedes mosquito (Aedes aegypti and Aedes albopictus) carrying dengue virus. The infection is caused by one of four dengue viruses (DENV 1-4).These mosquitos also spread Zika, chikungunya and other viruses. More than half of the world population is at risk of dengue. Dengue outbreaks are occurring in many countries of the world including Latin America, the Caribbean and Southeast Asia. Asia accounts for 75% of the dengue disease burden, followed by Latin America and Africa. Each year, about 58 million people get sick from a dengue infection and 13,500 die from it.Dengue fever is an acute viral infection characterized by fever and flu-like symptoms. Presentation varies ranging from no symptoms to a mild fever to a life-threatening shock and/or hemorrhage syndrome. Approximately 75% of individuals infected do not show any symptoms. Those who do show symptoms most commonly present with a mild to moderate, nonspecific fever 3-10 days after the bite of the infected mosquito. Other common symptoms along with the fever include a skin rash, severe headache, pain behind the eyes, in the muscles and joints. For many affected individuals, the disease is self-limited, ending with full recovery after symptoms resolve in 5-7 days.Up to 5% of all dengue affected individuals develop severe, life-threatening disease. Warning signs of progression to severe dengue include persistent vomiting, severe abdominal pain, rapid breathing, extreme fatigue, bleeding gums and a drop in blood pressure with position change.There are no specific medications for dengue and affected individuals are advised to stay well hydrated and control their fever with acetaminophen and tepid sponge baths. There are no medications to prevent dengue and travelers in endemic areas (high risk areas) are advised to avoid mosquito bites by staying indoors, wearing long clothing that cover their arm and legs, using bed nets and insect repellants.From 1975 to 2009, symptomatic dengue virus infections were classified according to the World Health Organization (WHO) guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). In 2009, the WHO issued a new guideline that classified cases as:IntroductionDengue infection is caused by one of four dengue viruses (DENV 1-4). Being infected from one dengue virus does not protect a person from the others. A primary dengue infection is when an individual is infected with the virus for the first time; a secondary infection is when the same individual is infected a second time with a different dengue virus. If the secondary dengue infection is more than 2 years after the primary infection, there is a higher risk of developing severe symptoms.Individuals with suspected dengue should seek help from a healthcare provider for early recognition of warning signs and prompt initiation of aggressive therapy when necessary.Severe dengue (previously known as dengue hemorrhagic fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today it affects over a hundred countries and has become one of the leading causes of hospitalization among individuals in these regions. | Overview of Dengue Fever. SummaryDengue fever is a virus transmitted by the bite of a female Aedes mosquito (Aedes aegypti and Aedes albopictus) carrying dengue virus. The infection is caused by one of four dengue viruses (DENV 1-4).These mosquitos also spread Zika, chikungunya and other viruses. More than half of the world population is at risk of dengue. Dengue outbreaks are occurring in many countries of the world including Latin America, the Caribbean and Southeast Asia. Asia accounts for 75% of the dengue disease burden, followed by Latin America and Africa. Each year, about 58 million people get sick from a dengue infection and 13,500 die from it.Dengue fever is an acute viral infection characterized by fever and flu-like symptoms. Presentation varies ranging from no symptoms to a mild fever to a life-threatening shock and/or hemorrhage syndrome. Approximately 75% of individuals infected do not show any symptoms. Those who do show symptoms most commonly present with a mild to moderate, nonspecific fever 3-10 days after the bite of the infected mosquito. Other common symptoms along with the fever include a skin rash, severe headache, pain behind the eyes, in the muscles and joints. For many affected individuals, the disease is self-limited, ending with full recovery after symptoms resolve in 5-7 days.Up to 5% of all dengue affected individuals develop severe, life-threatening disease. Warning signs of progression to severe dengue include persistent vomiting, severe abdominal pain, rapid breathing, extreme fatigue, bleeding gums and a drop in blood pressure with position change.There are no specific medications for dengue and affected individuals are advised to stay well hydrated and control their fever with acetaminophen and tepid sponge baths. There are no medications to prevent dengue and travelers in endemic areas (high risk areas) are advised to avoid mosquito bites by staying indoors, wearing long clothing that cover their arm and legs, using bed nets and insect repellants.From 1975 to 2009, symptomatic dengue virus infections were classified according to the World Health Organization (WHO) guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). In 2009, the WHO issued a new guideline that classified cases as:IntroductionDengue infection is caused by one of four dengue viruses (DENV 1-4). Being infected from one dengue virus does not protect a person from the others. A primary dengue infection is when an individual is infected with the virus for the first time; a secondary infection is when the same individual is infected a second time with a different dengue virus. If the secondary dengue infection is more than 2 years after the primary infection, there is a higher risk of developing severe symptoms.Individuals with suspected dengue should seek help from a healthcare provider for early recognition of warning signs and prompt initiation of aggressive therapy when necessary.Severe dengue (previously known as dengue hemorrhagic fever) was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand. Today it affects over a hundred countries and has become one of the leading causes of hospitalization among individuals in these regions. | 358 | Dengue Fever |
nord_358_1 | Symptoms of Dengue Fever | Dengue has a wide clinical spectrum with some individuals showing no symptoms, while others show mild symptoms to severe symptoms. The incubation period is a period between being infected with the virus to appearance of the first symptoms and for dengue it lasts 3-10 days. Approximately 25% experience a self-limited febrile illness, accompanied by mild-to-moderate haematological and biochemical abnormalities. Clinically relevant complications develop in a small proportion of these patients, including a systemic vascular leak syndrome, coagulation abnormalities that can be associated with bleeding, and organ involvement, typically hepatic or neurological. However, although these severe complications are infrequent the spectrum of clinical manifestations is broad. The most important risk factor for severe dengue is a prior dengue infection. The risk of developing severe dengue is greatest after a secondary infection with a different infecting type of dengue virus.The three classifications recommended by WHO are (1) dengue without warning signs, (2) dengue with warning signs and (3) severe dengueFor many affected individuals, the disease is self-limited, ending with full recovery after symptoms resolves in 5-7 days.When these warning signs are seen, the affected individual should be rushed to the emergency room or to the closest health care provider. | Symptoms of Dengue Fever. Dengue has a wide clinical spectrum with some individuals showing no symptoms, while others show mild symptoms to severe symptoms. The incubation period is a period between being infected with the virus to appearance of the first symptoms and for dengue it lasts 3-10 days. Approximately 25% experience a self-limited febrile illness, accompanied by mild-to-moderate haematological and biochemical abnormalities. Clinically relevant complications develop in a small proportion of these patients, including a systemic vascular leak syndrome, coagulation abnormalities that can be associated with bleeding, and organ involvement, typically hepatic or neurological. However, although these severe complications are infrequent the spectrum of clinical manifestations is broad. The most important risk factor for severe dengue is a prior dengue infection. The risk of developing severe dengue is greatest after a secondary infection with a different infecting type of dengue virus.The three classifications recommended by WHO are (1) dengue without warning signs, (2) dengue with warning signs and (3) severe dengueFor many affected individuals, the disease is self-limited, ending with full recovery after symptoms resolves in 5-7 days.When these warning signs are seen, the affected individual should be rushed to the emergency room or to the closest health care provider. | 358 | Dengue Fever |
nord_358_2 | Causes of Dengue Fever | Transmission
Dengue fever is a virus transmitted by the bite of a female Aedes mosquito (Aedes aegypti and Aedes albopictus) carrying dengue virus. The infection is caused by one of four dengue viruses (DENV 1-4). These mosquitos also spread Zika, chikungunya and other viruses.Once an individual is bit by an infected mosquito, the mosquito transmits the virus to that individual. The individual then becomes a carrier of the virus and the virus multiplies inside them. The virus circulates inside the blood of the infected person for 2-7 days during which time they become a source of the virus for uninfected mosquitos and can transmit the infection to another individual via Aedes mosquitos.When an individual recovers from the infection by one dengue virus, they become immune against that particular type of virus but can be infected by any of the other dengue virus types. | Causes of Dengue Fever. Transmission
Dengue fever is a virus transmitted by the bite of a female Aedes mosquito (Aedes aegypti and Aedes albopictus) carrying dengue virus. The infection is caused by one of four dengue viruses (DENV 1-4). These mosquitos also spread Zika, chikungunya and other viruses.Once an individual is bit by an infected mosquito, the mosquito transmits the virus to that individual. The individual then becomes a carrier of the virus and the virus multiplies inside them. The virus circulates inside the blood of the infected person for 2-7 days during which time they become a source of the virus for uninfected mosquitos and can transmit the infection to another individual via Aedes mosquitos.When an individual recovers from the infection by one dengue virus, they become immune against that particular type of virus but can be infected by any of the other dengue virus types. | 358 | Dengue Fever |
nord_358_3 | Affects of Dengue Fever | There is a high risk of contracting dengue throughout the tropics and subtropics and it is the leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia. Sporadic outbreaks with local transmission have also been seen in Florida, Hawaii and Texas along the border with Mexico. The geographic distribution of dengue is similar to that of malaria; however the risk for dengue is higher in urban and residential areas versus malaria which is found in rural areas. | Affects of Dengue Fever. There is a high risk of contracting dengue throughout the tropics and subtropics and it is the leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia. Sporadic outbreaks with local transmission have also been seen in Florida, Hawaii and Texas along the border with Mexico. The geographic distribution of dengue is similar to that of malaria; however the risk for dengue is higher in urban and residential areas versus malaria which is found in rural areas. | 358 | Dengue Fever |
nord_358_4 | Related disorders of Dengue Fever | Chikungunya
Chikungunya virus and dengue cause similar symptoms and are also transmitted by the same mosquito vector. Chikungunya is a viral infection transmitted by the bite of an infected mosquito. The most common symptoms are fever and joint pain, however other symptoms include headache, muscle pain, joint swelling and a rash. Symptoms typically being 3-7 days after being bitten by the infected mosquito. Most affected individuals feel better within a week, however in some people the joint pain may last for months or years. It primarily occurs in tropical areas of the world. (For more information on this disorder, choose “Chikungunya” as your search term in the Rare Disease Database.)Zika Virus
Zika virus and dengue have similar symptoms and are transmitted by the same mosquito vector. Zika is primarily transmitted by the bite of an infected mosquito, but it is also transmitted from a pregnant woman to her fetus, through sexual contact, blood transfusion and organ transplant. Zika infection during pregnancy is a cause of congenital abnormalities in the developing fetus and newborn including microcephaly (smaller head circumference than normal). It can also result in pregnancy complications such as fetal loss, stillbirth and preterm birth. Many infected individuals will not have symptoms or will only have mild symptoms including a fever, rash, headache joint pain, red eyes (conjunctivitis) and muscle pain lasting for several days to a week.Malaria
Malaria is a communicable parasitic disorder spread through the bite of the Anopheles mosquito. Major symptoms may vary depending on which species of parasite causes the infection and the stage of development of the parasite. Chills and fever commonly occur, although not every case follows the same pattern. Although the disorder was once thought to be under control throughout the world, malaria is a widespread infection especially in the tropics where certain types of mosquitos are becoming resistant to pesticides. The annual number of cases reported in the United States has increased in recent years. (For more information on this disorder, choose “Malaria” as your search term in the Rare Disease Database.)Other viruses
Other viruses that can cause a hemorrhagic fever include Ebola virus, Yellow fever virus, Crimean Congo hemorrhagic fever, Marburg virus etc. Viral hemorrhagic fevers are a group of illness that cause severe multisystem syndrome (multiple organ systems are affected) and also cause internal bleeding (hemorrhage). Blood tests may be used to identify the virus. | Related disorders of Dengue Fever. Chikungunya
Chikungunya virus and dengue cause similar symptoms and are also transmitted by the same mosquito vector. Chikungunya is a viral infection transmitted by the bite of an infected mosquito. The most common symptoms are fever and joint pain, however other symptoms include headache, muscle pain, joint swelling and a rash. Symptoms typically being 3-7 days after being bitten by the infected mosquito. Most affected individuals feel better within a week, however in some people the joint pain may last for months or years. It primarily occurs in tropical areas of the world. (For more information on this disorder, choose “Chikungunya” as your search term in the Rare Disease Database.)Zika Virus
Zika virus and dengue have similar symptoms and are transmitted by the same mosquito vector. Zika is primarily transmitted by the bite of an infected mosquito, but it is also transmitted from a pregnant woman to her fetus, through sexual contact, blood transfusion and organ transplant. Zika infection during pregnancy is a cause of congenital abnormalities in the developing fetus and newborn including microcephaly (smaller head circumference than normal). It can also result in pregnancy complications such as fetal loss, stillbirth and preterm birth. Many infected individuals will not have symptoms or will only have mild symptoms including a fever, rash, headache joint pain, red eyes (conjunctivitis) and muscle pain lasting for several days to a week.Malaria
Malaria is a communicable parasitic disorder spread through the bite of the Anopheles mosquito. Major symptoms may vary depending on which species of parasite causes the infection and the stage of development of the parasite. Chills and fever commonly occur, although not every case follows the same pattern. Although the disorder was once thought to be under control throughout the world, malaria is a widespread infection especially in the tropics where certain types of mosquitos are becoming resistant to pesticides. The annual number of cases reported in the United States has increased in recent years. (For more information on this disorder, choose “Malaria” as your search term in the Rare Disease Database.)Other viruses
Other viruses that can cause a hemorrhagic fever include Ebola virus, Yellow fever virus, Crimean Congo hemorrhagic fever, Marburg virus etc. Viral hemorrhagic fevers are a group of illness that cause severe multisystem syndrome (multiple organ systems are affected) and also cause internal bleeding (hemorrhage). Blood tests may be used to identify the virus. | 358 | Dengue Fever |
nord_358_5 | Diagnosis of Dengue Fever | Dengue can be suspected in an individual showing the symptoms listed above and if they reside in or have traveled within the past 2 weeks to an endemic area. Early clinical presentation of dengue is similar to other viral infections such as Zika and Chikungunya; therefore laboratory tests are useful in such cases.During the incubation period after the mosquito bites, the infected individual presents with no symptoms, however during this period the virus replicates, and an antibody response is developed.Clinical Testing and Work-Up
A blood test can be done to detect particles of the genetic material of the virus or it can indirectly detect the increase in antibody to fight off the virus. Depending on the duration of the illness and when the patient presents for the evaluation, the health care professional will decide which test is more appropriate.Performing a molecular and IgM antibody test can detect more cases than performing just one test during the first week after symptom onset.If an individual has symptoms of dengue and resides in or has traveled to an endemic area, they should seek help from a healthcare professional. During the initial evaluation, the healthcare provider will review the individual’s past medical history, recent travel history and vaccination record to determine the likelihood that the illness is due to dengue.If the infected individual presents to the healthcare provider within the first week of symptom onset, performing both a molecular test and an IgM antibody is preferred rather than one test.If the infected individual presents more than seven days after symptom onset, antibody testing is preferred.Dengue virus testing is not recommended for individuals who do not show symptoms after the incubation period. | Diagnosis of Dengue Fever. Dengue can be suspected in an individual showing the symptoms listed above and if they reside in or have traveled within the past 2 weeks to an endemic area. Early clinical presentation of dengue is similar to other viral infections such as Zika and Chikungunya; therefore laboratory tests are useful in such cases.During the incubation period after the mosquito bites, the infected individual presents with no symptoms, however during this period the virus replicates, and an antibody response is developed.Clinical Testing and Work-Up
A blood test can be done to detect particles of the genetic material of the virus or it can indirectly detect the increase in antibody to fight off the virus. Depending on the duration of the illness and when the patient presents for the evaluation, the health care professional will decide which test is more appropriate.Performing a molecular and IgM antibody test can detect more cases than performing just one test during the first week after symptom onset.If an individual has symptoms of dengue and resides in or has traveled to an endemic area, they should seek help from a healthcare professional. During the initial evaluation, the healthcare provider will review the individual’s past medical history, recent travel history and vaccination record to determine the likelihood that the illness is due to dengue.If the infected individual presents to the healthcare provider within the first week of symptom onset, performing both a molecular test and an IgM antibody is preferred rather than one test.If the infected individual presents more than seven days after symptom onset, antibody testing is preferred.Dengue virus testing is not recommended for individuals who do not show symptoms after the incubation period. | 358 | Dengue Fever |
nord_358_6 | Therapies of Dengue Fever | Treatment
There is no treatment for the virus that causes dengue, but the symptoms can be managed and treated. Management is largely supportive and maintaining adequate fluid volume in the blood vessels by keeping the patient hydrated. Infected individuals with mild symptoms in the absence of warning signs may be told by their doctor to stay home. In these cases, the individual should rest and drink plenty of fluids and watch for signs of dehydration (decreased urination, dry mouth or lips, cold hands or feet). Acetaminophen (Tylenol) can also be taken to relieve fever and aches. It is not recommended to take aspirin or NSAIDS (such as ibuprofen – Advil, Motrin) or Naproxen (Aleve) as they can increase the risk of bleeding. These individuals should also be aware of the warning signs of severe dengue infection and present to the hospital if warning signs are present or symptoms get worse.If the infected individual’s symptoms are more severe and presents with warning signs of severe infection, the doctor may decide to admit them to the hospital. Treatments in the hospital may include getting fluids through IV. Some individuals are at higher risk of developing severe dengue such as pregnant women, infants, elderly and individuals with asthma, obesity, diabetes, kidney failure or certain blood diseases.Prevention
The best way to prevent dengue is to stay away from mosquitos that carry it. This can be done byVaccination
CYD-TDV (Dengvaxia) is a vaccine that was approved in Europe in 2018 and by the US Food and Drug Administration (FDA) in 2019 for use in dengue endemic territories and only in children ages 9-16 years of age with evidence of a previous dengue infection. It is approved in other countries for people aged 9-45 years of age. It is not yet approved for travelers visiting dengue endemic areas and is not commercially available in the United States or Europe. The main approach to avoid dengue in travelers is to avoid mosquitos carrying the dengue virus.The World Health Organization (WHO), European Union and the Unites States regulatory agencies recommend the use of this vaccine only for individuals with laboratory evidence of previous dengue infection as a secondary infection can be more severe. Dengue vaccines are not 100% effective, however, and immunized individuals may present with a milder infection. The vaccine does not provide protection to people who have not had a dengue infection and should not be administered to seronegative persons. | Therapies of Dengue Fever. Treatment
There is no treatment for the virus that causes dengue, but the symptoms can be managed and treated. Management is largely supportive and maintaining adequate fluid volume in the blood vessels by keeping the patient hydrated. Infected individuals with mild symptoms in the absence of warning signs may be told by their doctor to stay home. In these cases, the individual should rest and drink plenty of fluids and watch for signs of dehydration (decreased urination, dry mouth or lips, cold hands or feet). Acetaminophen (Tylenol) can also be taken to relieve fever and aches. It is not recommended to take aspirin or NSAIDS (such as ibuprofen – Advil, Motrin) or Naproxen (Aleve) as they can increase the risk of bleeding. These individuals should also be aware of the warning signs of severe dengue infection and present to the hospital if warning signs are present or symptoms get worse.If the infected individual’s symptoms are more severe and presents with warning signs of severe infection, the doctor may decide to admit them to the hospital. Treatments in the hospital may include getting fluids through IV. Some individuals are at higher risk of developing severe dengue such as pregnant women, infants, elderly and individuals with asthma, obesity, diabetes, kidney failure or certain blood diseases.Prevention
The best way to prevent dengue is to stay away from mosquitos that carry it. This can be done byVaccination
CYD-TDV (Dengvaxia) is a vaccine that was approved in Europe in 2018 and by the US Food and Drug Administration (FDA) in 2019 for use in dengue endemic territories and only in children ages 9-16 years of age with evidence of a previous dengue infection. It is approved in other countries for people aged 9-45 years of age. It is not yet approved for travelers visiting dengue endemic areas and is not commercially available in the United States or Europe. The main approach to avoid dengue in travelers is to avoid mosquitos carrying the dengue virus.The World Health Organization (WHO), European Union and the Unites States regulatory agencies recommend the use of this vaccine only for individuals with laboratory evidence of previous dengue infection as a secondary infection can be more severe. Dengue vaccines are not 100% effective, however, and immunized individuals may present with a milder infection. The vaccine does not provide protection to people who have not had a dengue infection and should not be administered to seronegative persons. | 358 | Dengue Fever |
nord_359_0 | Overview of Dent Disease | SummaryDent disease is a rare genetic kidney disorder characterized by spillage of small proteins in the urine, increased levels of calcium in the urine, kidney calcifications (nephrocalcinosis), recurrent episodes of kidney stones (nephrolithiasis) and chronic kidney disease. Dent disease affects males almost exclusively. Symptoms usually appear during childhood, but some individuals may be undiagnosed well into adulthood. In some cases, the disorder may progressively worsen causing chronic kidney disease; in other cases affected individuals only experience mild or moderate disease into old age. Kidney disease can progressively worsen until the kidneys stop functioning (renal failure), although this usually does not occur until 30 to 50 years of age or later and will not occur at all in some individuals. Dent disease can be broken down into two subtypes. Dent disease type 1 is characterized by the previously-mentioned kidney symptoms. Dent disease type 2 is characterized by the same kidney symptoms, but individuals may have additional symptoms including mild intellectual disability, eye involvement or diminished muscle tone (hypotonia). Dent disease type 1 is caused by changes (mutations) in the CLCN5 gene. Dent disease type 2 is caused by mutations in the OCRL1 gene. Both of these genes are located on the X chromosome. These mutations may be inherited or occur randomly with no previous family history of the disorder (spontaneously). Dent disease is fully expressed only in males, although some females who carry the gene may develop mild manifestations such as spillage of small proteins in the urine, increased levels of calcium in the urine, or rarely kidney stones.IntroductionDent disease was first reported in the medical literature in 1964 by Drs. Dent and Friedman who described two unrelated boys with rickets. The disorder was eventually fully described by Dr. Oliver Wrong in 1990 who named the disease after his colleague and mentor Dr. Dent. Over the years Dent disease was referred to by other names including X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypercalciuric hypophosphatemic rickets, and idiopathic low-molecular-weight proteinuria with hypercalciuria and nephrocalcinosis. Generally, Dent disease is now broken into type 1 and type 2 based upon the specific genetic mutation present. There are other individuals with Dent disease who lack known mutations of these two genes (non 1/ non 2). | Overview of Dent Disease. SummaryDent disease is a rare genetic kidney disorder characterized by spillage of small proteins in the urine, increased levels of calcium in the urine, kidney calcifications (nephrocalcinosis), recurrent episodes of kidney stones (nephrolithiasis) and chronic kidney disease. Dent disease affects males almost exclusively. Symptoms usually appear during childhood, but some individuals may be undiagnosed well into adulthood. In some cases, the disorder may progressively worsen causing chronic kidney disease; in other cases affected individuals only experience mild or moderate disease into old age. Kidney disease can progressively worsen until the kidneys stop functioning (renal failure), although this usually does not occur until 30 to 50 years of age or later and will not occur at all in some individuals. Dent disease can be broken down into two subtypes. Dent disease type 1 is characterized by the previously-mentioned kidney symptoms. Dent disease type 2 is characterized by the same kidney symptoms, but individuals may have additional symptoms including mild intellectual disability, eye involvement or diminished muscle tone (hypotonia). Dent disease type 1 is caused by changes (mutations) in the CLCN5 gene. Dent disease type 2 is caused by mutations in the OCRL1 gene. Both of these genes are located on the X chromosome. These mutations may be inherited or occur randomly with no previous family history of the disorder (spontaneously). Dent disease is fully expressed only in males, although some females who carry the gene may develop mild manifestations such as spillage of small proteins in the urine, increased levels of calcium in the urine, or rarely kidney stones.IntroductionDent disease was first reported in the medical literature in 1964 by Drs. Dent and Friedman who described two unrelated boys with rickets. The disorder was eventually fully described by Dr. Oliver Wrong in 1990 who named the disease after his colleague and mentor Dr. Dent. Over the years Dent disease was referred to by other names including X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypercalciuric hypophosphatemic rickets, and idiopathic low-molecular-weight proteinuria with hypercalciuria and nephrocalcinosis. Generally, Dent disease is now broken into type 1 and type 2 based upon the specific genetic mutation present. There are other individuals with Dent disease who lack known mutations of these two genes (non 1/ non 2). | 359 | Dent Disease |
nord_359_1 | Symptoms of Dent Disease | The specific symptoms and severity of Dent disease can vary dramatically, even among individuals within the same family. Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about these disorders is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorders prevent physicians from developing a complete picture of associated symptoms and prognosis.Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.Common symptoms associated with Dent disease include elevated levels of proteins and calcium in the urine (proteinuria and hypercalciuria). The type of proteinuria seen in Dent disease is known as low-molecular-weight proteinuria, which is a characteristic finding of the disorder and not always detected in routine medical testing. Hypercalciuria and low molecular weight proteinuria may be the only symptoms that develop in some people.Affected individuals may also develop calcium deposits or calcifications in the kidney tissue (nephrocalcinosis) and/or experience recurrent episodes of kidney stone formation. Kidney stones can cause various symptoms including blood in the urine (hematuria), painful urination (dysuria), the urge to urinate often, abdominal pain (renal colic), blockage of the urinary tract, and repeated urinary tract infections. Eventually, the disorder can progress to cause chronic kidney disease with a progressive decline in kidney function. Symptoms associated with very advanced chronic kidney disease include loss of appetite, unintended weight loss, fatigue, and anemia. In some cases, sometimes as early as 30-50 years old, affected individuals can develop kidney failure and require dialysis or kidney transplantation.Some individuals with Dent disease may also develop bone disease such as softening of the bones (osteomalacia) and hypophosphatemic rickets, a condition caused by impaired transport of phosphate and altered vitamin D metabolism in the kidneys. In children, rickets is characterized by bowing deformity of the legs, as well as, growth plate abnormalities and progressive softening of the bones (called osteomalacia). . In children, growth rates may be slower than normal, frequently resulting in mild short stature. Children may also experience bone pain and difficulty walking. Because of bone abnormalities, both children and adults may have an increased risk of fractures.Some individuals with Dent disease have developed vitamin A deficiency, which can lead to impaired night vision and dry eyes (xerophthalmia). This can be corrected by vitamin A supplementation.DENT DISEASE TYPE 2
Dent disease type 2 is characterized by the same symptoms associated with Dent disease type 1. However, some affected individuals have developed additional symptoms including mild intellectual disability, hypotonia, and clouding of the lenses of the eyes (cataracts). Cataracts in Dent disease type 2 are classified as subclinical because they do not impair vision.Dent disease type 2 is caused by mutations in the same gene that causes Lowe syndrome, a rare multisystem disorder. Lowe syndrome is characterized by the kidney abnormalities that occur in Dent disease, but also additional findings affecting the eyes, brain and other organ systems. Some researchers believe that Dent disease type 2 represents the mild end of a disease spectrum that includes Lowe syndrome at the severe end. (For more information on Lowe syndrome, see the Related Disorders section of this report).FEMALE CARRIERS
Some females who inherited one of the mutations that cause Dent disease may develop mild manifestations of the disorder such as low-molecular-weight proteinuria and/or hypercalciuria. Kidney stones may be more common in female carriers, reported in 6 out of 14 Dent 1 mothers in one recent series. However, only one affected female has been reported in the literature to date whose disease progressed to kidney failure, however she did not have genetic testing to confirm the disease. | Symptoms of Dent Disease. The specific symptoms and severity of Dent disease can vary dramatically, even among individuals within the same family. Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about these disorders is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorders prevent physicians from developing a complete picture of associated symptoms and prognosis.Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.Common symptoms associated with Dent disease include elevated levels of proteins and calcium in the urine (proteinuria and hypercalciuria). The type of proteinuria seen in Dent disease is known as low-molecular-weight proteinuria, which is a characteristic finding of the disorder and not always detected in routine medical testing. Hypercalciuria and low molecular weight proteinuria may be the only symptoms that develop in some people.Affected individuals may also develop calcium deposits or calcifications in the kidney tissue (nephrocalcinosis) and/or experience recurrent episodes of kidney stone formation. Kidney stones can cause various symptoms including blood in the urine (hematuria), painful urination (dysuria), the urge to urinate often, abdominal pain (renal colic), blockage of the urinary tract, and repeated urinary tract infections. Eventually, the disorder can progress to cause chronic kidney disease with a progressive decline in kidney function. Symptoms associated with very advanced chronic kidney disease include loss of appetite, unintended weight loss, fatigue, and anemia. In some cases, sometimes as early as 30-50 years old, affected individuals can develop kidney failure and require dialysis or kidney transplantation.Some individuals with Dent disease may also develop bone disease such as softening of the bones (osteomalacia) and hypophosphatemic rickets, a condition caused by impaired transport of phosphate and altered vitamin D metabolism in the kidneys. In children, rickets is characterized by bowing deformity of the legs, as well as, growth plate abnormalities and progressive softening of the bones (called osteomalacia). . In children, growth rates may be slower than normal, frequently resulting in mild short stature. Children may also experience bone pain and difficulty walking. Because of bone abnormalities, both children and adults may have an increased risk of fractures.Some individuals with Dent disease have developed vitamin A deficiency, which can lead to impaired night vision and dry eyes (xerophthalmia). This can be corrected by vitamin A supplementation.DENT DISEASE TYPE 2
Dent disease type 2 is characterized by the same symptoms associated with Dent disease type 1. However, some affected individuals have developed additional symptoms including mild intellectual disability, hypotonia, and clouding of the lenses of the eyes (cataracts). Cataracts in Dent disease type 2 are classified as subclinical because they do not impair vision.Dent disease type 2 is caused by mutations in the same gene that causes Lowe syndrome, a rare multisystem disorder. Lowe syndrome is characterized by the kidney abnormalities that occur in Dent disease, but also additional findings affecting the eyes, brain and other organ systems. Some researchers believe that Dent disease type 2 represents the mild end of a disease spectrum that includes Lowe syndrome at the severe end. (For more information on Lowe syndrome, see the Related Disorders section of this report).FEMALE CARRIERS
Some females who inherited one of the mutations that cause Dent disease may develop mild manifestations of the disorder such as low-molecular-weight proteinuria and/or hypercalciuria. Kidney stones may be more common in female carriers, reported in 6 out of 14 Dent 1 mothers in one recent series. However, only one affected female has been reported in the literature to date whose disease progressed to kidney failure, however she did not have genetic testing to confirm the disease. | 359 | Dent Disease |
nord_359_2 | Causes of Dent Disease | Dent disease type 1 is caused by a mutation in the CLCN5 gene; Dent disease type 2 is caused by mutations in the OCRL1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.In most cases, male children inherit the disorder from a carrier mother who has no symptoms or extremely mild symptoms of the disorder. When a mother is a known carrier of the CLCN5 or the OCRL1 mutation, there is a 50% chance of passing that mutation on to her children. Males who inherited a mutation will have the disorder; females who inherited the mutation will be carriers. In extremely rare cases, the mutation that causes the disorder occurs randomly for no apparent reason (de novo mutation). Affected males will not pass the disorder onto sons (who inherit the Y chromosome from fathers), but will pass the mutation on to all their daughters (who will become carriers).Random X-chromosome inactivation is a normal process in females. Females have two X chromosomes, whereas males have one X chromosome and one Y chromosome. In females, certain disease traits on the X chromosome such as a mutated gene may be “masked” by the normal gene on the other X chromosome (random X-chromosome inactivation). Basically, in each cell of the body one X chromosome is active and one is turned off or “silenced.” This occurs randomly and generally happens as a 50-50 split. However, in some cases, females may have favorable X-inactivation, in which the affected X chromosome is silenced in most of the cells. In such cases, they may not develop any symptoms or only have mild symptoms of the disorder. In other cases, females may have unfavorable X-inactivation, in which the unaffected X chromosome is silenced in most of the cells. In such cases, affected females may develop various symptoms associated with Dent disease, but this has only occurred in extremely rare cases.The CLCN5 and OCRL1 genes create (encode) specific enzymes that are necessary for the proper function of the kidneys. Mutations in these genes result in reduced activity of these enzymes. The enzyme product produced by the CLCN5 gene is believed to be expressed heavily in the kidneys, including within the proximal tubules, the tiny tubes that serve as the primary site of protein reabsorption in the nephron, in the cortical collecting tubules and the loop of Henle. Nephrons are hair-sized structures that are the basic units of the kidneys and remove waste from the blood. The proximal tubules are essential for the proper reabsorption of several important filtered substances such as proteins. Dysfunction of the proximal tubules is believed to play an important role in the development of Dent disease. The exact functions of the enzyme product produced by the OCRL1 gene are not fully understood; however it is known that it is also involved in reabsorption of proteins and recycling of receptors in proximal tubules. More research is necessary to determine the specific functions of these enzymes and how their deficiency contributes to the development of Dent disease.Some individuals with Dent disease do not have mutations in either the CLCN5 or OCRL1 genes, suggesting that additional subtypes of Dent disease caused by mutations in as yet unidentified genes most likely exist. | Causes of Dent Disease. Dent disease type 1 is caused by a mutation in the CLCN5 gene; Dent disease type 2 is caused by mutations in the OCRL1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.In most cases, male children inherit the disorder from a carrier mother who has no symptoms or extremely mild symptoms of the disorder. When a mother is a known carrier of the CLCN5 or the OCRL1 mutation, there is a 50% chance of passing that mutation on to her children. Males who inherited a mutation will have the disorder; females who inherited the mutation will be carriers. In extremely rare cases, the mutation that causes the disorder occurs randomly for no apparent reason (de novo mutation). Affected males will not pass the disorder onto sons (who inherit the Y chromosome from fathers), but will pass the mutation on to all their daughters (who will become carriers).Random X-chromosome inactivation is a normal process in females. Females have two X chromosomes, whereas males have one X chromosome and one Y chromosome. In females, certain disease traits on the X chromosome such as a mutated gene may be “masked” by the normal gene on the other X chromosome (random X-chromosome inactivation). Basically, in each cell of the body one X chromosome is active and one is turned off or “silenced.” This occurs randomly and generally happens as a 50-50 split. However, in some cases, females may have favorable X-inactivation, in which the affected X chromosome is silenced in most of the cells. In such cases, they may not develop any symptoms or only have mild symptoms of the disorder. In other cases, females may have unfavorable X-inactivation, in which the unaffected X chromosome is silenced in most of the cells. In such cases, affected females may develop various symptoms associated with Dent disease, but this has only occurred in extremely rare cases.The CLCN5 and OCRL1 genes create (encode) specific enzymes that are necessary for the proper function of the kidneys. Mutations in these genes result in reduced activity of these enzymes. The enzyme product produced by the CLCN5 gene is believed to be expressed heavily in the kidneys, including within the proximal tubules, the tiny tubes that serve as the primary site of protein reabsorption in the nephron, in the cortical collecting tubules and the loop of Henle. Nephrons are hair-sized structures that are the basic units of the kidneys and remove waste from the blood. The proximal tubules are essential for the proper reabsorption of several important filtered substances such as proteins. Dysfunction of the proximal tubules is believed to play an important role in the development of Dent disease. The exact functions of the enzyme product produced by the OCRL1 gene are not fully understood; however it is known that it is also involved in reabsorption of proteins and recycling of receptors in proximal tubules. More research is necessary to determine the specific functions of these enzymes and how their deficiency contributes to the development of Dent disease.Some individuals with Dent disease do not have mutations in either the CLCN5 or OCRL1 genes, suggesting that additional subtypes of Dent disease caused by mutations in as yet unidentified genes most likely exist. | 359 | Dent Disease |
nord_359_3 | Affects of Dent Disease | The exact incidence and prevalence of Dent disease is unknown. Dent disease type 1 has been reported in approximately 250 families. Dent disease type 2 has been reported in approximately 25 individuals. Because some affected individuals go undiagnosed or misdiagnosed, determining these disorders’ true frequency in the general population is difficult. Dent disease is fully expressed in males only. Dent disease may be recognized during childhood, while other cases can remain undiagnosed well into adulthood. | Affects of Dent Disease. The exact incidence and prevalence of Dent disease is unknown. Dent disease type 1 has been reported in approximately 250 families. Dent disease type 2 has been reported in approximately 25 individuals. Because some affected individuals go undiagnosed or misdiagnosed, determining these disorders’ true frequency in the general population is difficult. Dent disease is fully expressed in males only. Dent disease may be recognized during childhood, while other cases can remain undiagnosed well into adulthood. | 359 | Dent Disease |
nord_359_4 | Related disorders of Dent Disease | Symptoms of the following disorders can be similar to those of Dent disease. Comparisons may be useful for a differential diagnosis.There are several rare genetic disorders characterized by the formation of stones in the kidney or urinary tract sometimes in childhood similar to those seen in Dent disease. Such disorders include the primary hyperoxalurias, familial hypercalciuria-hypomagnesaemia-nephrocalcinosis (Michelis-Castrillo syndrome), adenine phosphoribosyltransferase (APRT) deficiency, and cystinuria. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)A variety of disorders are characterized by renal Fanconi syndrome. Examples include genetic disorders such as cystinosis, hereditary fructose intolerance, galactosemia, tyronsinemia, Wilson disease, and various glycogen storage diseases. Renal Fanconi syndrome can also be acquired during life due to the use of certain drugs (e.g. valproate, deferasirox, cisplastin, ifosfamide) and secondary to certain kidneys diseases, cancers such as multiple myeloma, Sjogren syndrome, or hyperparathyroidism. In children, exposure to heavy metals can also cause renal Fanconi syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Lowe syndrome, also known as oculocerebrorenal syndrome of Lowe, is a rare genetic disorder characterized by vision problems including clouding of the lenses of the eyes (cataracts) that are present at birth, kidney problems that usually develop in the first year of life, and brain abnormalities that are associated with intellectual disabilities. The specific symptoms and severity of the disorder can vary greatly from one person to another. Lowe syndrome is inherited as an X-linked trait. Lowe syndrome is caused by mutations in the same gene (OCRL1) that causes Dent disease type 2. The disorder is fully expressed in males only. (For more information on this disorder, choose “Lowe” as your search term in the Rare Disease Database.) | Related disorders of Dent Disease. Symptoms of the following disorders can be similar to those of Dent disease. Comparisons may be useful for a differential diagnosis.There are several rare genetic disorders characterized by the formation of stones in the kidney or urinary tract sometimes in childhood similar to those seen in Dent disease. Such disorders include the primary hyperoxalurias, familial hypercalciuria-hypomagnesaemia-nephrocalcinosis (Michelis-Castrillo syndrome), adenine phosphoribosyltransferase (APRT) deficiency, and cystinuria. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)A variety of disorders are characterized by renal Fanconi syndrome. Examples include genetic disorders such as cystinosis, hereditary fructose intolerance, galactosemia, tyronsinemia, Wilson disease, and various glycogen storage diseases. Renal Fanconi syndrome can also be acquired during life due to the use of certain drugs (e.g. valproate, deferasirox, cisplastin, ifosfamide) and secondary to certain kidneys diseases, cancers such as multiple myeloma, Sjogren syndrome, or hyperparathyroidism. In children, exposure to heavy metals can also cause renal Fanconi syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Lowe syndrome, also known as oculocerebrorenal syndrome of Lowe, is a rare genetic disorder characterized by vision problems including clouding of the lenses of the eyes (cataracts) that are present at birth, kidney problems that usually develop in the first year of life, and brain abnormalities that are associated with intellectual disabilities. The specific symptoms and severity of the disorder can vary greatly from one person to another. Lowe syndrome is inherited as an X-linked trait. Lowe syndrome is caused by mutations in the same gene (OCRL1) that causes Dent disease type 2. The disorder is fully expressed in males only. (For more information on this disorder, choose “Lowe” as your search term in the Rare Disease Database.) | 359 | Dent Disease |
nord_359_5 | Diagnosis of Dent Disease | A diagnosis of Dent disease is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis may be suspected in individuals with high levels of low-molecular-weight proteins in the urine, excess levels of calcium in the urine and one of the following: nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease, or evidence of X-linked recessive inheritance.Clinical Testing and Workup
Chemical analysis of urine samples may reveal elevated levels of low-molecular-weight proteins and calcium. A biopsy of affected kidney tissue may also reveal changes indicative of Dent disease, although findings may not be specific and are sometimes reported out as focal segmental glomerulosclerosis (FSGS) or focal global glomerulosclerosis. A biopsy involves the surgical removal and microscopic examination of a piece of affected tissue. A kidney biopsy is not necessary for the diagnosis of Dent disease since laboratory findings and genetic testing can be sufficient to make the diagnosis. However kidney biopsies are often performed in patients who have unexplained kidney disease and significant proteinuria, so that many patients with Dent disease are biopsied before the final diagnosis is made.A diagnosis of Dent disease can be confirmed through molecular genetic testing. Molecular genetic testing can detect mutations in the two specific genes known to cause Dent disease, but is not always necessary to make a clinical diagnosis of Dent disease if typical findings are present (for example low molecular weight proteinuria and hypercalciuria in male patient). However, genetic testing is generally recommended today since it is becoming increasingly recognized that other genetic causes of nephrocalcinosis and chronic kidney disease share clinical features with Dent disease. | Diagnosis of Dent Disease. A diagnosis of Dent disease is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis may be suspected in individuals with high levels of low-molecular-weight proteins in the urine, excess levels of calcium in the urine and one of the following: nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease, or evidence of X-linked recessive inheritance.Clinical Testing and Workup
Chemical analysis of urine samples may reveal elevated levels of low-molecular-weight proteins and calcium. A biopsy of affected kidney tissue may also reveal changes indicative of Dent disease, although findings may not be specific and are sometimes reported out as focal segmental glomerulosclerosis (FSGS) or focal global glomerulosclerosis. A biopsy involves the surgical removal and microscopic examination of a piece of affected tissue. A kidney biopsy is not necessary for the diagnosis of Dent disease since laboratory findings and genetic testing can be sufficient to make the diagnosis. However kidney biopsies are often performed in patients who have unexplained kidney disease and significant proteinuria, so that many patients with Dent disease are biopsied before the final diagnosis is made.A diagnosis of Dent disease can be confirmed through molecular genetic testing. Molecular genetic testing can detect mutations in the two specific genes known to cause Dent disease, but is not always necessary to make a clinical diagnosis of Dent disease if typical findings are present (for example low molecular weight proteinuria and hypercalciuria in male patient). However, genetic testing is generally recommended today since it is becoming increasingly recognized that other genetic causes of nephrocalcinosis and chronic kidney disease share clinical features with Dent disease. | 359 | Dent Disease |
nord_359_6 | Therapies of Dent Disease | TreatmentThe treatment of Dent disease is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, general internists, specialists who assess and treat problems of the kidneys (nephrologists), specialists who assess and treat problems of the urinary tract (urologists), dieticians, and other healthcare professionals may need to systematically and comprehensively plan an affect individual’s treatment. Genetic counseling may be of benefit for affected individuals and their families.There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of these diseases, 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 Dent disease.Medications known as thiazide diuretics may be used to treat individuals with Dent disease to prevent the recurrence of kidney stones and to lower levels of calcium in the urine. However, these medications can potentially cause significant adverse side effects.Additional medications known as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have been used in children with other causes of chronic kidney disease associated with elevated levels of proteins in their urine to prevent or delay a further decline in kidney function. The effectiveness of these medications in children with Dent disease is unclear.If vitamin D is used to treat rickets in a patient with Dent disease, it must be done cautiously because excess amounts of vitamin D can increase calcium levels in the urine. Growth failure in children may be treated with growth hormone supplementation. A high citrate diet or citrate supplements in pill or liquid form have also been used to treat some individuals with Dent disease, based on the observation that a high citrate diet slows progression of kidney disease in a mouse model of Dent disease, although the efficacy of citrate is unproven in humans.If kidney function continues to decline, or in cases where an individual is first diagnosed with Dent disease after the development of kidney failure, additional more aggressive treatment may be required including hemodialysis, peritoneal dialysis, and a kidney transplant. | Therapies of Dent Disease. TreatmentThe treatment of Dent disease is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, general internists, specialists who assess and treat problems of the kidneys (nephrologists), specialists who assess and treat problems of the urinary tract (urologists), dieticians, and other healthcare professionals may need to systematically and comprehensively plan an affect individual’s treatment. Genetic counseling may be of benefit for affected individuals and their families.There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of these diseases, 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 Dent disease.Medications known as thiazide diuretics may be used to treat individuals with Dent disease to prevent the recurrence of kidney stones and to lower levels of calcium in the urine. However, these medications can potentially cause significant adverse side effects.Additional medications known as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have been used in children with other causes of chronic kidney disease associated with elevated levels of proteins in their urine to prevent or delay a further decline in kidney function. The effectiveness of these medications in children with Dent disease is unclear.If vitamin D is used to treat rickets in a patient with Dent disease, it must be done cautiously because excess amounts of vitamin D can increase calcium levels in the urine. Growth failure in children may be treated with growth hormone supplementation. A high citrate diet or citrate supplements in pill or liquid form have also been used to treat some individuals with Dent disease, based on the observation that a high citrate diet slows progression of kidney disease in a mouse model of Dent disease, although the efficacy of citrate is unproven in humans.If kidney function continues to decline, or in cases where an individual is first diagnosed with Dent disease after the development of kidney failure, additional more aggressive treatment may be required including hemodialysis, peritoneal dialysis, and a kidney transplant. | 359 | Dent Disease |
nord_360_0 | Overview of Dentin Dysplasia Type I | Dentin dysplasia type I is an inherited disorder characterized by atypical development of the “dentin” of a person's teeth. Dentin makes up most of the tooth and is the bone-like material under the enamel. It serves to contain the pulp of the tooth. The pulp is a soft tissue that is well supplied with blood vessels and nerves. This disorder is also known as radicular dentin dysplasia because the underdeveloped, abnormal pulp tissue is predominately in the roots of the teeth. The teeth lack pulp chambers or have half-moon shaped pulp chambers in short or abnormally shaped roots. The condition may affect juvenile as well as adult teeth and, since the roots are abnormally short, usually leads to the premature loss of teeth. The color of the teeth is usually normal. | Overview of Dentin Dysplasia Type I. Dentin dysplasia type I is an inherited disorder characterized by atypical development of the “dentin” of a person's teeth. Dentin makes up most of the tooth and is the bone-like material under the enamel. It serves to contain the pulp of the tooth. The pulp is a soft tissue that is well supplied with blood vessels and nerves. This disorder is also known as radicular dentin dysplasia because the underdeveloped, abnormal pulp tissue is predominately in the roots of the teeth. The teeth lack pulp chambers or have half-moon shaped pulp chambers in short or abnormally shaped roots. The condition may affect juvenile as well as adult teeth and, since the roots are abnormally short, usually leads to the premature loss of teeth. The color of the teeth is usually normal. | 360 | Dentin Dysplasia Type I |
nord_360_1 | Symptoms of Dentin Dysplasia Type I | Some people with dentin dysplasia type I have teeth with a bluish-brown shine. In most instances, however, the teeth have normally colored enamel. It is clear from X-ray photos that the tooth pulp chambers in the roots are unusually small, half-moon shaped or lacking altogether. The roots are very short and may appear to be dark (radiolucent) on X-rays.Both the baby teeth and the permanent teeth are affected. The teeth are often poorly aligned and can be chipped easily. Without treatment, persons with dentin dysplasia type I may lose their teeth by age 30-40. | Symptoms of Dentin Dysplasia Type I. Some people with dentin dysplasia type I have teeth with a bluish-brown shine. In most instances, however, the teeth have normally colored enamel. It is clear from X-ray photos that the tooth pulp chambers in the roots are unusually small, half-moon shaped or lacking altogether. The roots are very short and may appear to be dark (radiolucent) on X-rays.Both the baby teeth and the permanent teeth are affected. The teeth are often poorly aligned and can be chipped easily. Without treatment, persons with dentin dysplasia type I may lose their teeth by age 30-40. | 360 | Dentin Dysplasia Type I |
nord_360_2 | Causes of Dentin Dysplasia Type I | Dentin dysplasia is inherited as an autosomal dominant trait. The defective gene has not been identified or traced to a particular site on a particular chromosome. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and 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.Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. | Causes of Dentin Dysplasia Type I. Dentin dysplasia is inherited as an autosomal dominant trait. The defective gene has not been identified or traced to a particular site on a particular chromosome. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and 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.Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. | 360 | Dentin Dysplasia Type I |
nord_360_3 | Affects of Dentin Dysplasia Type I | Dentin dysplasia type I appears to affect about 1 in 100,000 persons. Males and females are apparently equally at risk. | Affects of Dentin Dysplasia Type I. Dentin dysplasia type I appears to affect about 1 in 100,000 persons. Males and females are apparently equally at risk. | 360 | Dentin Dysplasia Type I |
nord_360_4 | Related disorders of Dentin Dysplasia Type I | Symptoms of the following disorders can be similar to dentin dysplasia type I. Comparisons may be useful for a differential diagnosis:Dentin dysplasia, type II, also known as coronal dentin dysplasia since it affects the crown of the tooth rather than the root, is another autosomal dominant hereditary disorder. It is characterized by brownish-blue shiny baby teeth with reduced root canals and normal appearing permanent teeth. (For more information on this disorder, choose “Coronal Dentin Dysplasia” as your search term in the Rare Disease Database.)Dentinogenesis imperfecta is yet another hereditary disorder of dentin formation and tooth development transmitted as an autosomal dominant trait. It is characterized by bluish-brown or brown, opalescent baby and permanent teeth. The tooth enamel breaks and wears off easily. In affected adults, only roots may remain. X-rays usually show the absence of dental pulp chambers and root canals. (For more information on thia disorder, choose “Dentinogenesis imperfecta” as your search term in the Rare Disease Database.)Hypophosphatemic vitamin D-resistant rickets is inherited as an X-linked dominant trait. In addition to affecting the kidney and its function in sustaining the balance of phosphate ions between blood, cells and urine, this disorder results in short stature and bowed legs. The development of the teeth may be severely delayed and the pulp chambers are large. In addition, the dentin is streaked with fissures that crack easily leading to infection and abscesses. | Related disorders of Dentin Dysplasia Type I. Symptoms of the following disorders can be similar to dentin dysplasia type I. Comparisons may be useful for a differential diagnosis:Dentin dysplasia, type II, also known as coronal dentin dysplasia since it affects the crown of the tooth rather than the root, is another autosomal dominant hereditary disorder. It is characterized by brownish-blue shiny baby teeth with reduced root canals and normal appearing permanent teeth. (For more information on this disorder, choose “Coronal Dentin Dysplasia” as your search term in the Rare Disease Database.)Dentinogenesis imperfecta is yet another hereditary disorder of dentin formation and tooth development transmitted as an autosomal dominant trait. It is characterized by bluish-brown or brown, opalescent baby and permanent teeth. The tooth enamel breaks and wears off easily. In affected adults, only roots may remain. X-rays usually show the absence of dental pulp chambers and root canals. (For more information on thia disorder, choose “Dentinogenesis imperfecta” as your search term in the Rare Disease Database.)Hypophosphatemic vitamin D-resistant rickets is inherited as an X-linked dominant trait. In addition to affecting the kidney and its function in sustaining the balance of phosphate ions between blood, cells and urine, this disorder results in short stature and bowed legs. The development of the teeth may be severely delayed and the pulp chambers are large. In addition, the dentin is streaked with fissures that crack easily leading to infection and abscesses. | 360 | Dentin Dysplasia Type I |
nord_360_5 | Diagnosis of Dentin Dysplasia Type I | Diagnosis is usually based on x-rays taken when some abnormality is suspected. | Diagnosis of Dentin Dysplasia Type I. Diagnosis is usually based on x-rays taken when some abnormality is suspected. | 360 | Dentin Dysplasia Type I |
nord_360_6 | Therapies of Dentin Dysplasia Type I | TreatmentThe affected teeth are usually treated by a dentist specializing in the care o. the roots and pulp of the teeth (endodontists). Filling the tips of the root canals may extend the period of time that the affected teeth remain fixed to the jaw. Sometimes, the affected teeth must be extracted and replaced with dentures.Genetic counseling is recommended for families of children with dentin dysplasia type I. | Therapies of Dentin Dysplasia Type I. TreatmentThe affected teeth are usually treated by a dentist specializing in the care o. the roots and pulp of the teeth (endodontists). Filling the tips of the root canals may extend the period of time that the affected teeth remain fixed to the jaw. Sometimes, the affected teeth must be extracted and replaced with dentures.Genetic counseling is recommended for families of children with dentin dysplasia type I. | 360 | Dentin Dysplasia Type I |
nord_361_0 | Overview of Dentin Dysplasia Type II | Dentin dysplasia type II, also known as coronal dentin dysplasia, is a rare genetic disorder that affects the teeth. It is characterized by abnormal development (dysplasia) of dentin. Dentin is the hard tissue found beneath the enamel that surrounds and protects the pulp and forms the major part of teeth. Affected children may exhibit brownish-blue discoloration of baby teeth (primary or deciduous teeth) and obliteration of the pulp chambers. Permanent teeth are usually unaffected or only mildly affected. Dentin dysplasia type II only affects the teeth. The disorder is caused by changes (mutations) of the DSPP gene.Dentin dysplasia type II belongs to a group of disorders known as the hereditary dentin disorders. In 1973, a physician and his colleagues defined five disorders characterized by inherited dentin defects (Shields classification). Many physicians have noted that the Shields classification is out of date. As new research reveals genetic mutations and better defines these disorders, a new classification system will be warranted. Unfortunately, the current understanding of these disorders is insufficient to allow the creation of this updated classification. | Overview of Dentin Dysplasia Type II. Dentin dysplasia type II, also known as coronal dentin dysplasia, is a rare genetic disorder that affects the teeth. It is characterized by abnormal development (dysplasia) of dentin. Dentin is the hard tissue found beneath the enamel that surrounds and protects the pulp and forms the major part of teeth. Affected children may exhibit brownish-blue discoloration of baby teeth (primary or deciduous teeth) and obliteration of the pulp chambers. Permanent teeth are usually unaffected or only mildly affected. Dentin dysplasia type II only affects the teeth. The disorder is caused by changes (mutations) of the DSPP gene.Dentin dysplasia type II belongs to a group of disorders known as the hereditary dentin disorders. In 1973, a physician and his colleagues defined five disorders characterized by inherited dentin defects (Shields classification). Many physicians have noted that the Shields classification is out of date. As new research reveals genetic mutations and better defines these disorders, a new classification system will be warranted. Unfortunately, the current understanding of these disorders is insufficient to allow the creation of this updated classification. | 361 | Dentin Dysplasia Type II |
nord_361_1 | Symptoms of Dentin Dysplasia Type II | Dentin dysplasia type II is a dental abnormality characterized by abnormal development (dysplasia) of dentin. Within the interior of a tooth is pulp – a specialized tissue that contains nerves, blood vessels, and lymphatic vessels. Pulp is surrounded by a hard dental tissue known as dentin, which forms the primary material of the tooth. The exposed region of the tooth above the gum (also known as the crown or “coronal region”) is covered by enamel, which is harder than dentin, while the root is covered by a bone-like rigid connective tissue known as cementum. Dentin protects the pulp chamber and provides support for enamel and cementum.In individuals with dentin dysplasia type II, the baby teeth may be discolored appearing to be yellow, brown, grey-amber, or a brownish-blue color. The teeth are sometimes described as having a translucent “opalescence”. (Opalescence refers to a milky, opal-like display of colors in reflected light.) In most cases, the permanent (secondary) teeth have a normal color.When the dentin layer beneath the enamel crown is too weak to support it, the enamel will tend to wear away (abrade) and fall out prematurely.In addition to being normal in color, permanent teeth are also normal in shape and size. However, they also have characteristic abnormalities of the pulp chambers. More specifically, on dental x-rays, pulp chambers appear unusually “flame shaped” and often have abnormal extensions toward the roots (i.e., “thistle-tube” shaped pulp chambers). In addition, the pulp chambers often contain numerous pulp stones, which are abnormal deposits of calcium salts (calcifications). With age, the pulp chambers of the permanent teeth may become partially obliterated. Evidence suggests that root formation in the permanent teeth is usually normal.In rare cases, some individuals with dentin dysplasia type II may develop mild tooth discoloration or abnormally rounded (bulbous) crowns. If these abnormalities are pronounced in the permanent teeth, then the diagnosis changes to dentinogenesis imperfecta type II (DGI-II). | Symptoms of Dentin Dysplasia Type II. Dentin dysplasia type II is a dental abnormality characterized by abnormal development (dysplasia) of dentin. Within the interior of a tooth is pulp – a specialized tissue that contains nerves, blood vessels, and lymphatic vessels. Pulp is surrounded by a hard dental tissue known as dentin, which forms the primary material of the tooth. The exposed region of the tooth above the gum (also known as the crown or “coronal region”) is covered by enamel, which is harder than dentin, while the root is covered by a bone-like rigid connective tissue known as cementum. Dentin protects the pulp chamber and provides support for enamel and cementum.In individuals with dentin dysplasia type II, the baby teeth may be discolored appearing to be yellow, brown, grey-amber, or a brownish-blue color. The teeth are sometimes described as having a translucent “opalescence”. (Opalescence refers to a milky, opal-like display of colors in reflected light.) In most cases, the permanent (secondary) teeth have a normal color.When the dentin layer beneath the enamel crown is too weak to support it, the enamel will tend to wear away (abrade) and fall out prematurely.In addition to being normal in color, permanent teeth are also normal in shape and size. However, they also have characteristic abnormalities of the pulp chambers. More specifically, on dental x-rays, pulp chambers appear unusually “flame shaped” and often have abnormal extensions toward the roots (i.e., “thistle-tube” shaped pulp chambers). In addition, the pulp chambers often contain numerous pulp stones, which are abnormal deposits of calcium salts (calcifications). With age, the pulp chambers of the permanent teeth may become partially obliterated. Evidence suggests that root formation in the permanent teeth is usually normal.In rare cases, some individuals with dentin dysplasia type II may develop mild tooth discoloration or abnormally rounded (bulbous) crowns. If these abnormalities are pronounced in the permanent teeth, then the diagnosis changes to dentinogenesis imperfecta type II (DGI-II). | 361 | Dentin Dysplasia Type II |
nord_361_2 | Causes of Dentin Dysplasia Type II | Dentin dysplasia type II is caused by mutations of the dentin sialophosphoprotein (DSPP) gene. This mutation is inherited in an autosomal dominant pattern. 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 (changed) 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.Researchers have determined two classes of DSPP mutations that cause inherited dentin defects. The first class involves mutations that alter the beginning part of the protein (N-terminus) in a way that reduces its ability to be secreted properly and is toxic to the cell that produces it. This first class of DSPP mutations causes DGI-II & DGI-III, which are closely related to DD-II, only more severe. The second class of mutations (-1 frameshifts) cause the second (C-terminal) half of the DSPP protein to change from being very acidic in character to very hydrophobic and is also toxic to the cell that produces it. This second class of DSPP mutations can cause DD-II, as well as DGI-II & III. It is not understood why this second class of DSPP mutations sometimes result in the more minor dentin phenotype (DD-II), and sometimes the more severe phenotypes of DGI-II and DGI-III. Deletion of single copy of DSPP when the retained copy is normal does not cause a dental phenotype, although a person with such a loss is predicted to be a carrier of the recessive form of DGI-III. | Causes of Dentin Dysplasia Type II. Dentin dysplasia type II is caused by mutations of the dentin sialophosphoprotein (DSPP) gene. This mutation is inherited in an autosomal dominant pattern. 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 (changed) 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.Researchers have determined two classes of DSPP mutations that cause inherited dentin defects. The first class involves mutations that alter the beginning part of the protein (N-terminus) in a way that reduces its ability to be secreted properly and is toxic to the cell that produces it. This first class of DSPP mutations causes DGI-II & DGI-III, which are closely related to DD-II, only more severe. The second class of mutations (-1 frameshifts) cause the second (C-terminal) half of the DSPP protein to change from being very acidic in character to very hydrophobic and is also toxic to the cell that produces it. This second class of DSPP mutations can cause DD-II, as well as DGI-II & III. It is not understood why this second class of DSPP mutations sometimes result in the more minor dentin phenotype (DD-II), and sometimes the more severe phenotypes of DGI-II and DGI-III. Deletion of single copy of DSPP when the retained copy is normal does not cause a dental phenotype, although a person with such a loss is predicted to be a carrier of the recessive form of DGI-III. | 361 | Dentin Dysplasia Type II |
nord_361_3 | Affects of Dentin Dysplasia Type II | Dentin dysplasia type II affects males and females in equal numbers. The exact incidence and prevalence of dentin dysplasia type II is unknown. It occurs more frequently than dentin dysplasia type I, which is estimated to affect 1 in 100,000 people in the general population.Abnormalities of dentin dysplasia have been known by many other names in the medical literature including rootless teeth, anomalous dysplasia of dentin, opalescent dentin, pulpless teeth, and thistle-tube teeth. | Affects of Dentin Dysplasia Type II. Dentin dysplasia type II affects males and females in equal numbers. The exact incidence and prevalence of dentin dysplasia type II is unknown. It occurs more frequently than dentin dysplasia type I, which is estimated to affect 1 in 100,000 people in the general population.Abnormalities of dentin dysplasia have been known by many other names in the medical literature including rootless teeth, anomalous dysplasia of dentin, opalescent dentin, pulpless teeth, and thistle-tube teeth. | 361 | Dentin Dysplasia Type II |
nord_361_4 | Related disorders of Dentin Dysplasia Type II | Symptoms of the following disorders can be similar to those of dentin dysplasia type II. Comparisons may be useful for a differential diagnosis.Inherited dentin defects are a group of rare inherited disorders that primarily affect dentin. In addition to dentin dysplasia type II, these disorders included dentin dysplasia type I and dentinogenesis imperfecta (DGI) types I, II and III. These disorders share similar symptoms including tooth discoloration, abnormalities of the pulp chambers, abnormally rounded (bulbous) crowns, and wearing away and premature loss of teeth. These disorders affect both the baby teeth and permanent teeth. Dentin dysplasia type II and dentinogenesis imperfecta types II and III are due to mutations in the DSPP gene (allelic disorders). These disorders of dentin defects are inherited as autosomal dominant traits. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | Related disorders of Dentin Dysplasia Type II. Symptoms of the following disorders can be similar to those of dentin dysplasia type II. Comparisons may be useful for a differential diagnosis.Inherited dentin defects are a group of rare inherited disorders that primarily affect dentin. In addition to dentin dysplasia type II, these disorders included dentin dysplasia type I and dentinogenesis imperfecta (DGI) types I, II and III. These disorders share similar symptoms including tooth discoloration, abnormalities of the pulp chambers, abnormally rounded (bulbous) crowns, and wearing away and premature loss of teeth. These disorders affect both the baby teeth and permanent teeth. Dentin dysplasia type II and dentinogenesis imperfecta types II and III are due to mutations in the DSPP gene (allelic disorders). These disorders of dentin defects are inherited as autosomal dominant traits. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | 361 | Dentin Dysplasia Type II |
nord_361_5 | Diagnosis of Dentin Dysplasia Type II | A diagnosis of coronal dentin dysplasia is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. X-rays may reveal abnormal coronal pulp formation, obliteration of the pulp chambers, pulp stones or thistle-shaped deformity of the pulp chamber. | Diagnosis of Dentin Dysplasia Type II. A diagnosis of coronal dentin dysplasia is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. X-rays may reveal abnormal coronal pulp formation, obliteration of the pulp chambers, pulp stones or thistle-shaped deformity of the pulp chamber. | 361 | Dentin Dysplasia Type II |
nord_361_6 | Therapies of Dentin Dysplasia Type II | TreatmentThe treatment of coronal dentin dysplasia is directed toward the specific symptoms that are apparent in each individual. Because permanent teeth are often unaffected, no specific or unusually dental therapy is necessary. Recommended treatment may include regular monitoring by dental specialists and ongoing preventive dental care.Genetic counseling may be of benefit for affected individuals and their families. | Therapies of Dentin Dysplasia Type II. TreatmentThe treatment of coronal dentin dysplasia is directed toward the specific symptoms that are apparent in each individual. Because permanent teeth are often unaffected, no specific or unusually dental therapy is necessary. Recommended treatment may include regular monitoring by dental specialists and ongoing preventive dental care.Genetic counseling may be of benefit for affected individuals and their families. | 361 | Dentin Dysplasia Type II |
nord_362_0 | Overview of Dentinogenesis Imperfecta Type III | Dentinogenesis imperfecta type III (DGI-III) is one of five distinct, hereditary disorders of dentin development affecting the teeth. Dentin is the hard, bone-like material that makes up most of a tooth and lies under the enamel serving to protect the soft, pulp tissue. These heritable dentin disorders may affect only the teeth or may be associated with the condition known as osteogenesis imperfecta. Whether this association is present is a major criterion in the classification of dentinogenesis imperfecta into three types.The teeth of people who have inherited one of the DGIs are usually pale-colored and lustrous (opalescent). They are awkwardly formed and situated in the gums; they wear away readily and break easily.Patients with DGI type I also are affected by osteogenesis imperfecta, and the whites of their eyes (sclera) are blue in color. Patients with DGI type II are NOT affected by osteogenesis imperfecta, but show the other clinical signs. Patients with DGI type III appear to be limited, in large measure, to a population in the region around Brandywine in southern Maryland. | Overview of Dentinogenesis Imperfecta Type III. Dentinogenesis imperfecta type III (DGI-III) is one of five distinct, hereditary disorders of dentin development affecting the teeth. Dentin is the hard, bone-like material that makes up most of a tooth and lies under the enamel serving to protect the soft, pulp tissue. These heritable dentin disorders may affect only the teeth or may be associated with the condition known as osteogenesis imperfecta. Whether this association is present is a major criterion in the classification of dentinogenesis imperfecta into three types.The teeth of people who have inherited one of the DGIs are usually pale-colored and lustrous (opalescent). They are awkwardly formed and situated in the gums; they wear away readily and break easily.Patients with DGI type I also are affected by osteogenesis imperfecta, and the whites of their eyes (sclera) are blue in color. Patients with DGI type II are NOT affected by osteogenesis imperfecta, but show the other clinical signs. Patients with DGI type III appear to be limited, in large measure, to a population in the region around Brandywine in southern Maryland. | 362 | Dentinogenesis Imperfecta Type III |
nord_362_1 | Symptoms of Dentinogenesis Imperfecta Type III | Dentinogenesis imperfecta type III is characterized by rapid erosion of the crowns in baby and permanent teeth. Dental pulp inside several teeth may be exposed. This pulp may be opalescent, smooth, and amber colored. Pulp chambers and root canals may appear very large on X-ray photos of baby teeth. Permanent teeth may have a reduction or even complete loss of the pulp chambers and root canals. Carriers of the gene for this disorder may have teeth that appear normal. However, upon examination their teeth have only an extremely thin ivory layer and an enlarged pulp chamber (shell teeth). Pitting of the tooth enamel may occur in the permanent teeth of patients. | Symptoms of Dentinogenesis Imperfecta Type III. Dentinogenesis imperfecta type III is characterized by rapid erosion of the crowns in baby and permanent teeth. Dental pulp inside several teeth may be exposed. This pulp may be opalescent, smooth, and amber colored. Pulp chambers and root canals may appear very large on X-ray photos of baby teeth. Permanent teeth may have a reduction or even complete loss of the pulp chambers and root canals. Carriers of the gene for this disorder may have teeth that appear normal. However, upon examination their teeth have only an extremely thin ivory layer and an enlarged pulp chamber (shell teeth). Pitting of the tooth enamel may occur in the permanent teeth of patients. | 362 | Dentinogenesis Imperfecta Type III |
nord_362_2 | Causes of Dentinogenesis Imperfecta Type III | Dentinogenesis imperfecta type III is inherited as an autosomal dominant trait. The abnormal (mutated) gene has been tracked to a site on the long arm of chromosome 4 at band 21.3 (4q21.3). Interestingly, this gene is thought to code for two major dentin proteins — dentin sialoprotein and dentin phosphoprotein. Hence, the gene has been called DSPP for dentin sialophosphoprotein.Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. 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.Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son. X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive. | Causes of Dentinogenesis Imperfecta Type III. Dentinogenesis imperfecta type III is inherited as an autosomal dominant trait. The abnormal (mutated) gene has been tracked to a site on the long arm of chromosome 4 at band 21.3 (4q21.3). Interestingly, this gene is thought to code for two major dentin proteins — dentin sialoprotein and dentin phosphoprotein. Hence, the gene has been called DSPP for dentin sialophosphoprotein.Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. 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.Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son. X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive. | 362 | Dentinogenesis Imperfecta Type III |
nord_362_3 | Affects of Dentinogenesis Imperfecta Type III | Patients with dentinogenesis imperfecta type III are affected in a ratio of approximately 55 males to 45 females. Symptoms begin as soon as baby teeth erupt. It tends to run in families. The disorder was first found to occur in people who lived in Brandywine, MD, but it can also affect persons of Ashkenazi Jewish heritage.There do not appear to be reliable numbers for the prevalence or incidence of each of the types of dentinogenesis imperfecta. However as a whole, the disorder affects 1 in 6000 to 8,000 people. | Affects of Dentinogenesis Imperfecta Type III. Patients with dentinogenesis imperfecta type III are affected in a ratio of approximately 55 males to 45 females. Symptoms begin as soon as baby teeth erupt. It tends to run in families. The disorder was first found to occur in people who lived in Brandywine, MD, but it can also affect persons of Ashkenazi Jewish heritage.There do not appear to be reliable numbers for the prevalence or incidence of each of the types of dentinogenesis imperfecta. However as a whole, the disorder affects 1 in 6000 to 8,000 people. | 362 | Dentinogenesis Imperfecta Type III |
nord_362_4 | Related disorders of Dentinogenesis Imperfecta Type III | Symptoms of the following disorders can be similar to those of dentinogenesis imperfecta, type III. Comparisons may be useful for a differential diagnosis:Radicular dentin dysplasia is a genetic disorder characterized by abnormal formation of tooth ivory (dentin). The teeth lack pulp chambers, or have half-moon shaped pulp chambers in short or abnormally shaped roots. The color of the teeth is usually normal. (For more information, choose “Dentin Dysplasia” as your search term in the Rare Disease Database.)Coronal dentin dysplasia is a genetic disorder characterized by brownish-blue opalescent baby teeth and permanent teeth that appear normal. The baby teeth in children affected by this disorder contain obliterated pulp chambers and reduced root canals. Permanent teeth also have abnormalities. (For more information, choose “Dentin Dysplasia” as your search term in the Rare Disease Database.)Osteogenesis imperfecta, or brittle bone disease, is a group of hereditary connective tissue disorders characterized by unusual bone fragility and tendency to fracture. Dentinogenesis imperfecta is one of the features of osteogenesis imperfecta. (For more information, choose “Osteogenesis Imperfecta” as your search term in the Rare Disease Database.)Dentinogenesis imperfecta type I (DGI-I) is also known as opalescent dentin, opalescent teeth with osteogenesis imperfecta, dentinogenesis imperfecta, Shields type I, usually is accompanied by an increase in the incidence of broken long bones of the legs and/or arms because of the increased brittleness of these bones. The whites of the eye (sclera) are blue. The opalescent teeth may be blue-gray or a yellowish-brown color. The dentin is soft and erodes easily. On X-ray examination, the chamber that usually holds the dental pulp appears to be closed off or filled in.Dentinogenesis imperfecta type II (DGI-II), also known as Capdepont teeth and/or hereditary opalescent dentin) is an inherited disorder characterized by blue-gray or amber brown, opalescent teeth, without brittleness of the bones. Dental X-rays indicate the teeth have bulbous crowns, roots are narrower than normal, and pulp chambers and root canals are smaller than normal or completely absent. The tooth enamel splits readily from the ivory when the upper teeth close forcefully against the lower teeth, as in chewing or biting. This is the most common form of DGI encountered. | Related disorders of Dentinogenesis Imperfecta Type III. Symptoms of the following disorders can be similar to those of dentinogenesis imperfecta, type III. Comparisons may be useful for a differential diagnosis:Radicular dentin dysplasia is a genetic disorder characterized by abnormal formation of tooth ivory (dentin). The teeth lack pulp chambers, or have half-moon shaped pulp chambers in short or abnormally shaped roots. The color of the teeth is usually normal. (For more information, choose “Dentin Dysplasia” as your search term in the Rare Disease Database.)Coronal dentin dysplasia is a genetic disorder characterized by brownish-blue opalescent baby teeth and permanent teeth that appear normal. The baby teeth in children affected by this disorder contain obliterated pulp chambers and reduced root canals. Permanent teeth also have abnormalities. (For more information, choose “Dentin Dysplasia” as your search term in the Rare Disease Database.)Osteogenesis imperfecta, or brittle bone disease, is a group of hereditary connective tissue disorders characterized by unusual bone fragility and tendency to fracture. Dentinogenesis imperfecta is one of the features of osteogenesis imperfecta. (For more information, choose “Osteogenesis Imperfecta” as your search term in the Rare Disease Database.)Dentinogenesis imperfecta type I (DGI-I) is also known as opalescent dentin, opalescent teeth with osteogenesis imperfecta, dentinogenesis imperfecta, Shields type I, usually is accompanied by an increase in the incidence of broken long bones of the legs and/or arms because of the increased brittleness of these bones. The whites of the eye (sclera) are blue. The opalescent teeth may be blue-gray or a yellowish-brown color. The dentin is soft and erodes easily. On X-ray examination, the chamber that usually holds the dental pulp appears to be closed off or filled in.Dentinogenesis imperfecta type II (DGI-II), also known as Capdepont teeth and/or hereditary opalescent dentin) is an inherited disorder characterized by blue-gray or amber brown, opalescent teeth, without brittleness of the bones. Dental X-rays indicate the teeth have bulbous crowns, roots are narrower than normal, and pulp chambers and root canals are smaller than normal or completely absent. The tooth enamel splits readily from the ivory when the upper teeth close forcefully against the lower teeth, as in chewing or biting. This is the most common form of DGI encountered. | 362 | Dentinogenesis Imperfecta Type III |
nord_362_5 | Diagnosis of Dentinogenesis Imperfecta Type III | X-rays of the teeth are key to the diagnosis after a thorough family history and clinical examination. | Diagnosis of Dentinogenesis Imperfecta Type III. X-rays of the teeth are key to the diagnosis after a thorough family history and clinical examination. | 362 | Dentinogenesis Imperfecta Type III |
nord_362_6 | Therapies of Dentinogenesis Imperfecta Type III | TreatmentTreatment of children with dentinogenesis imperfecta type III consists of placement of a full set of dental crowns over the teeth. In adults, all teeth may be extracted carefully by elevation and replaced with a full set of dentures. It is recommended that treatment is started early to improve the facial appearance of young patients.Genetic counseling is recommended for families of children with dentinogenesis imperfecta. | Therapies of Dentinogenesis Imperfecta Type III. TreatmentTreatment of children with dentinogenesis imperfecta type III consists of placement of a full set of dental crowns over the teeth. In adults, all teeth may be extracted carefully by elevation and replaced with a full set of dentures. It is recommended that treatment is started early to improve the facial appearance of young patients.Genetic counseling is recommended for families of children with dentinogenesis imperfecta. | 362 | Dentinogenesis Imperfecta Type III |
nord_363_0 | Overview of Denys-Drash Syndrome | Denys-Drash syndrome (DDS) is characterized by abnormal kidney function (congenital nephropathy), a cancerous tumor of the kidney called Wilms tumor, and disorders of sexual development in affected males. Most affected females have normal genitalia. DDS is a genetic disorder caused by mutations in the Wilms tumor suppressor gene, WT1. | Overview of Denys-Drash Syndrome. Denys-Drash syndrome (DDS) is characterized by abnormal kidney function (congenital nephropathy), a cancerous tumor of the kidney called Wilms tumor, and disorders of sexual development in affected males. Most affected females have normal genitalia. DDS is a genetic disorder caused by mutations in the Wilms tumor suppressor gene, WT1. | 363 | Denys-Drash Syndrome |
nord_363_1 | Symptoms of Denys-Drash Syndrome | The initial symptoms of DDS may be similar to nephrotic syndrome and include edema, abdominal distention and recurrent infections, sometimes present at birth but more often developing between 1 and 2 years of age. Many affected children develop high blood pressure (hypertension). The kidney abnormality that results in abnormal kidney function is termed diffuse mesangial sclerosis and usually results in a progression to renal failure during the first three years of life.Wilms tumor occurs in approximately 90% of affected individuals and is sometimes the first clinical sign of the disease. Signs of Wilms tumor can include abdominal swelling, blood in the urine, decreased urination, low-grade fever, loss of appetite, paleness, weight loss and lethargy.Disorders of sexual development also occur in males with DDS and are rare in females with this condition. These are conditions in which a boy has normal male chromosomes (46, XY), but the external genitals are incompletely formed, ambiguous, or clearly female. Testes may be normal, malformed, absent, or internal (undescended). Affected individuals of both genders are at risk for cancers of the testes or ovaries. | Symptoms of Denys-Drash Syndrome. The initial symptoms of DDS may be similar to nephrotic syndrome and include edema, abdominal distention and recurrent infections, sometimes present at birth but more often developing between 1 and 2 years of age. Many affected children develop high blood pressure (hypertension). The kidney abnormality that results in abnormal kidney function is termed diffuse mesangial sclerosis and usually results in a progression to renal failure during the first three years of life.Wilms tumor occurs in approximately 90% of affected individuals and is sometimes the first clinical sign of the disease. Signs of Wilms tumor can include abdominal swelling, blood in the urine, decreased urination, low-grade fever, loss of appetite, paleness, weight loss and lethargy.Disorders of sexual development also occur in males with DDS and are rare in females with this condition. These are conditions in which a boy has normal male chromosomes (46, XY), but the external genitals are incompletely formed, ambiguous, or clearly female. Testes may be normal, malformed, absent, or internal (undescended). Affected individuals of both genders are at risk for cancers of the testes or ovaries. | 363 | Denys-Drash Syndrome |
nord_363_2 | Causes of Denys-Drash Syndrome | DDS is a genetic disorder caused by mutations in the Wilms tumor suppressor gene, WT1. The vast majority of the mutations occur in one of two areas of the gene located on chromosome 11, called exon 8 or exon 9. While mutations in a single copy of the WT1 gene are sufficient to produce nephropathy and disorders of sexual development, Wilms tumor results from mutations in both copies of the WT1 gene. The abnormal product of a single copy of mutant WT1 gene interferes with the function of the unaffected copy of the WT1 gene and changes its normal regulatory function. This is sufficient to produce nephropathy and disorders of sexual development. In contrast, Wilms tumor is a result of two independent events (two-hit hypothesis) that sequentially lead to loss of function of both copies of the WT1 gene. The first mutation in a single copy of the WT1 gene (first hit) leads to persistence of an undifferentiated tissue in the developing kidney, called mesenchyme. Subsequently, another mutation (second hit) in the second copy causes uncontrolled cell growth in the kidney and Wilms tumor formation.Most cases of DDS are not inherited from a parent and occur as the result of a new gene mutation. | Causes of Denys-Drash Syndrome. DDS is a genetic disorder caused by mutations in the Wilms tumor suppressor gene, WT1. The vast majority of the mutations occur in one of two areas of the gene located on chromosome 11, called exon 8 or exon 9. While mutations in a single copy of the WT1 gene are sufficient to produce nephropathy and disorders of sexual development, Wilms tumor results from mutations in both copies of the WT1 gene. The abnormal product of a single copy of mutant WT1 gene interferes with the function of the unaffected copy of the WT1 gene and changes its normal regulatory function. This is sufficient to produce nephropathy and disorders of sexual development. In contrast, Wilms tumor is a result of two independent events (two-hit hypothesis) that sequentially lead to loss of function of both copies of the WT1 gene. The first mutation in a single copy of the WT1 gene (first hit) leads to persistence of an undifferentiated tissue in the developing kidney, called mesenchyme. Subsequently, another mutation (second hit) in the second copy causes uncontrolled cell growth in the kidney and Wilms tumor formation.Most cases of DDS are not inherited from a parent and occur as the result of a new gene mutation. | 363 | Denys-Drash Syndrome |
nord_363_3 | Affects of Denys-Drash Syndrome | The prevalence of DDS is not known. Over 200 cases have been reported in the medical literature. | Affects of Denys-Drash Syndrome. The prevalence of DDS is not known. Over 200 cases have been reported in the medical literature. | 363 | Denys-Drash Syndrome |
nord_363_4 | Related disorders of Denys-Drash Syndrome | Signs of the following disorders can be similar to those of Denys-Drash syndrome. Comparisons may be useful for a differential diagnosis.Wilms tumor is the most common form of abdominal malignancy in children and accounts for 6 to 8 percent of all childhood cancers. Typically, this disease first appears by 3-4 years of age, but has also been diagnosed in adulthood. Wilms tumor can often be treated successfully, depending on the stage of the tumor at detection and the age and general health of the child. (For more information on this disorder, choose “Wilms tumor” as your search term in the Rare Disease Database.)WAGR syndrome is a rare genetic syndrome in which there is a predisposition to several conditions, including certain malignancies, distinctive eye abnormalities, and/or intellectual disability. “WAGR” is an acronym for the characteristic abnormalities associated with the syndrome. The acronym stands for (W)ilms’ Tumor; (A)niridia, partial or complete absence of the colored region of the eye(s) (iris or irides); (G) Genitourinary abnormalities, such as undescended testicles or hypospadias in males, or internal genital or urinary anomalies in females; and Mental (R)etardation. A combination of two or more of these conditions is usually present in most individuals with WAGR syndrome. Affected individuals have a deletion of the WT1 gene. (For more information on this disorder, choose “WAGR” as your search term in the Rare Disease Database.)Frasier syndrome is characterized by congenital nephropathy, female genitalia in individuals with normal male chromosomes (46, XY) and underdeveloped gonads (streak gonads) that may become cancerous. Nephropathy leads to end-stage renal disease late in childhood. Frasier syndrome is caused by mutations in the WT1 gene. | Related disorders of Denys-Drash Syndrome. Signs of the following disorders can be similar to those of Denys-Drash syndrome. Comparisons may be useful for a differential diagnosis.Wilms tumor is the most common form of abdominal malignancy in children and accounts for 6 to 8 percent of all childhood cancers. Typically, this disease first appears by 3-4 years of age, but has also been diagnosed in adulthood. Wilms tumor can often be treated successfully, depending on the stage of the tumor at detection and the age and general health of the child. (For more information on this disorder, choose “Wilms tumor” as your search term in the Rare Disease Database.)WAGR syndrome is a rare genetic syndrome in which there is a predisposition to several conditions, including certain malignancies, distinctive eye abnormalities, and/or intellectual disability. “WAGR” is an acronym for the characteristic abnormalities associated with the syndrome. The acronym stands for (W)ilms’ Tumor; (A)niridia, partial or complete absence of the colored region of the eye(s) (iris or irides); (G) Genitourinary abnormalities, such as undescended testicles or hypospadias in males, or internal genital or urinary anomalies in females; and Mental (R)etardation. A combination of two or more of these conditions is usually present in most individuals with WAGR syndrome. Affected individuals have a deletion of the WT1 gene. (For more information on this disorder, choose “WAGR” as your search term in the Rare Disease Database.)Frasier syndrome is characterized by congenital nephropathy, female genitalia in individuals with normal male chromosomes (46, XY) and underdeveloped gonads (streak gonads) that may become cancerous. Nephropathy leads to end-stage renal disease late in childhood. Frasier syndrome is caused by mutations in the WT1 gene. | 363 | Denys-Drash Syndrome |
nord_363_5 | Diagnosis of Denys-Drash Syndrome | DDS is diagnosed by physical signs and symptoms, laboratory tests, imaging studies, and kidney biopsy to document diffuse mesangial sclerosis. Molecular genetic testing for the WT1 gene is available to confirm the diagnosis. | Diagnosis of Denys-Drash Syndrome. DDS is diagnosed by physical signs and symptoms, laboratory tests, imaging studies, and kidney biopsy to document diffuse mesangial sclerosis. Molecular genetic testing for the WT1 gene is available to confirm the diagnosis. | 363 | Denys-Drash Syndrome |
nord_363_6 | Therapies of Denys-Drash Syndrome | Treatment
The treatment of DDS is supportive and requires consultation with a pediatric nephrologist, pediatric oncologist, pediatric surgeon, pediatric endocrinologist and geneticist.Medical care involves management of fluids and electrolytes, treatment for hypertension and chemotherapy for Wilms tumor, if present. Prophylactic removal of kidneys (nephrectomy) is recommended when the diagnosis of DDS is made prior to development of Wilms tumor. Renal replacement therapy, including dialysis and/or kidney transplantation, is recommended following end-stage renal failure or nephrectomy. Surgical removal of internal reproductive organs (gonadectomy) is recommended because of the high risk for gonadal malignancy.Genetic counseling is recommended. Other treatment is symptomatic and supportive. | Therapies of Denys-Drash Syndrome. Treatment
The treatment of DDS is supportive and requires consultation with a pediatric nephrologist, pediatric oncologist, pediatric surgeon, pediatric endocrinologist and geneticist.Medical care involves management of fluids and electrolytes, treatment for hypertension and chemotherapy for Wilms tumor, if present. Prophylactic removal of kidneys (nephrectomy) is recommended when the diagnosis of DDS is made prior to development of Wilms tumor. Renal replacement therapy, including dialysis and/or kidney transplantation, is recommended following end-stage renal failure or nephrectomy. Surgical removal of internal reproductive organs (gonadectomy) is recommended because of the high risk for gonadal malignancy.Genetic counseling is recommended. Other treatment is symptomatic and supportive. | 363 | Denys-Drash Syndrome |
nord_364_0 | Overview of Deoxyhypusine Synthase Disorder | SummaryDeoxyhypusine synthase (DHPS) disorder is a rare disorder characterized by neurodevelopmental delay and seizures beginning in childhood. This autosomal recessive genetic condition is caused by changes (mutations or variants) in the DHPS gene. | Overview of Deoxyhypusine Synthase Disorder. SummaryDeoxyhypusine synthase (DHPS) disorder is a rare disorder characterized by neurodevelopmental delay and seizures beginning in childhood. This autosomal recessive genetic condition is caused by changes (mutations or variants) in the DHPS gene. | 364 | Deoxyhypusine Synthase Disorder |
nord_364_1 | Symptoms of Deoxyhypusine Synthase Disorder | Mutations in the DHPS gene are thought to be responsible for the following: | Symptoms of Deoxyhypusine Synthase Disorder. Mutations in the DHPS gene are thought to be responsible for the following: | 364 | Deoxyhypusine Synthase Disorder |
nord_364_2 | Causes of Deoxyhypusine Synthase Disorder | DHPS disorder is inherited in an autosomal recessive pattern. 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.DHPS disorder is caused by changes (mutations or variants) in the DHPS gene. The DHPS gene is responsible for production of the deoxyhypusine synthase enzyme that is involved in the synthesis of an unusual amino acid called hypusine. This aminio acid is found in only a single protein, eukaryotypic translation initiation factor-5A (EIF5A). EIF5A promotes translation, elongation, or production of many proteins in the body.Several individuals with two different mutations in DHPS gene have been identified.Two siblings have both been diagnosed with c.888 +1 G>A mutation and p.N131S. Another child has been diagnosed with c.912_917delTTACAT, p.Y305_I306del and p.N131S. The fact that all three children share the p.N131S mutation with a loss of function mutation suggests that it is extremely likely that this is the correct diagnosis.Studies have shown that the c.888 +1 G>A mutation results in abnormal splicing of the DHPS gene and leads to loss of function of that copy of the DHPS gene.The p.Tyr305_Ile306del mutation present in the third child also leads to loss of function of the DHPS gene.The p.N131S mutation leads to greatly decreased DHPS enzyme activity but not complete loss of function. | Causes of Deoxyhypusine Synthase Disorder. DHPS disorder is inherited in an autosomal recessive pattern. 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.DHPS disorder is caused by changes (mutations or variants) in the DHPS gene. The DHPS gene is responsible for production of the deoxyhypusine synthase enzyme that is involved in the synthesis of an unusual amino acid called hypusine. This aminio acid is found in only a single protein, eukaryotypic translation initiation factor-5A (EIF5A). EIF5A promotes translation, elongation, or production of many proteins in the body.Several individuals with two different mutations in DHPS gene have been identified.Two siblings have both been diagnosed with c.888 +1 G>A mutation and p.N131S. Another child has been diagnosed with c.912_917delTTACAT, p.Y305_I306del and p.N131S. The fact that all three children share the p.N131S mutation with a loss of function mutation suggests that it is extremely likely that this is the correct diagnosis.Studies have shown that the c.888 +1 G>A mutation results in abnormal splicing of the DHPS gene and leads to loss of function of that copy of the DHPS gene.The p.Tyr305_Ile306del mutation present in the third child also leads to loss of function of the DHPS gene.The p.N131S mutation leads to greatly decreased DHPS enzyme activity but not complete loss of function. | 364 | Deoxyhypusine Synthase Disorder |
nord_364_3 | Affects of Deoxyhypusine Synthase Disorder | As of November 2022, DHPS disorder has been diagnosed in less than ten individuals. | Affects of Deoxyhypusine Synthase Disorder. As of November 2022, DHPS disorder has been diagnosed in less than ten individuals. | 364 | Deoxyhypusine Synthase Disorder |
nord_364_4 | Related disorders of Deoxyhypusine Synthase Disorder | There are many disorders that can cause signs and symptoms similar to those seen in people with DHPS disorder. These include a wide variety of other genetic neurodevelopmental disorders. The signs and symptoms of DHPS disorder alone are not varied enough to distinguish the disorder from many of these other, similar disorders. | Related disorders of Deoxyhypusine Synthase Disorder. There are many disorders that can cause signs and symptoms similar to those seen in people with DHPS disorder. These include a wide variety of other genetic neurodevelopmental disorders. The signs and symptoms of DHPS disorder alone are not varied enough to distinguish the disorder from many of these other, similar disorders. | 364 | Deoxyhypusine Synthase Disorder |
nord_364_5 | Diagnosis of Deoxyhypusine Synthase Disorder | A diagnosis of DHPS disorder is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Children with mild or moderate intellectual disability and speech development problems, but no other anomalies may be suspected of having DHPS disorder. A diagnosis is confirmed through molecular genetic testing for mutations in the DHPS gene.Clinical Testing and Workup
Molecular genetic testing can detect disease-causing variations in the DHPS gene but is available only as a diagnostic service at specialized laboratories. Doctors will take a blood sample of individuals suspected of having a DHPS disorder and the sample will undergo whole exome sequencing (WES). WES is a molecular genetic testing method that examines the genes in humans that contain instructions for creating proteins (protein-encoding genes). This is called the exome. WES can detect variations in the DHPS gene that are known to cause disease, or variations in other genes known to cause symptoms similar to this disorder.Affected individuals may undergo additional tests before molecular genetic testing to rule other conditions, or after molecular genetic testing to assess the extent of the disease.Neurologic examination is important for individuals with the symptoms of DHPS disorder. Neurologic examination helps identify the specific features affecting a person. Laboratory tests, neurophysiologic testing, and neuroimaging; routine laboratory studies (such as blood counts, serum electrolytes, and tests of kidney, liver, and endocrine functions); and analysis of cerebrospinal fluid (obtained by “spinal tap”) may be conducted to help exclude alternate and co-existing diagnoses. | Diagnosis of Deoxyhypusine Synthase Disorder. A diagnosis of DHPS disorder is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Children with mild or moderate intellectual disability and speech development problems, but no other anomalies may be suspected of having DHPS disorder. A diagnosis is confirmed through molecular genetic testing for mutations in the DHPS gene.Clinical Testing and Workup
Molecular genetic testing can detect disease-causing variations in the DHPS gene but is available only as a diagnostic service at specialized laboratories. Doctors will take a blood sample of individuals suspected of having a DHPS disorder and the sample will undergo whole exome sequencing (WES). WES is a molecular genetic testing method that examines the genes in humans that contain instructions for creating proteins (protein-encoding genes). This is called the exome. WES can detect variations in the DHPS gene that are known to cause disease, or variations in other genes known to cause symptoms similar to this disorder.Affected individuals may undergo additional tests before molecular genetic testing to rule other conditions, or after molecular genetic testing to assess the extent of the disease.Neurologic examination is important for individuals with the symptoms of DHPS disorder. Neurologic examination helps identify the specific features affecting a person. Laboratory tests, neurophysiologic testing, and neuroimaging; routine laboratory studies (such as blood counts, serum electrolytes, and tests of kidney, liver, and endocrine functions); and analysis of cerebrospinal fluid (obtained by “spinal tap”) may be conducted to help exclude alternate and co-existing diagnoses. | 364 | Deoxyhypusine Synthase Disorder |
nord_364_6 | Therapies of Deoxyhypusine Synthase Disorder | The treatment of DHPS disorder 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 specialize in diagnosing and treating disorders of the brain and central nervous system in children (pediatric neurologists) and adults (neurologists), speech therapists, physical therapists, occupational therapists, and other healthcare professionals may need to systematically and comprehensively plan treatment.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.Following an initial diagnosis, a developmental assessment may be performed and appropriate occupational, physical, and speech therapies be instituted. Speech therapy is required and can include one-on-one sessions with a speech therapist, combined sessions where children learn language and social skills as a group, and the use of augmentative and alternative communication (AAC). AAC includes the use of communication devices, both high tech and low-tech ones, that can help children express thoughts, wants, needs and ideas.Periodic reassessments and adjustment of services should be provided with all children. Additional medical, social, and/or vocational services including specialized learning programs may be necessary.Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well. | Therapies of Deoxyhypusine Synthase Disorder. The treatment of DHPS disorder 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 specialize in diagnosing and treating disorders of the brain and central nervous system in children (pediatric neurologists) and adults (neurologists), speech therapists, physical therapists, occupational therapists, and other healthcare professionals may need to systematically and comprehensively plan treatment.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.Following an initial diagnosis, a developmental assessment may be performed and appropriate occupational, physical, and speech therapies be instituted. Speech therapy is required and can include one-on-one sessions with a speech therapist, combined sessions where children learn language and social skills as a group, and the use of augmentative and alternative communication (AAC). AAC includes the use of communication devices, both high tech and low-tech ones, that can help children express thoughts, wants, needs and ideas.Periodic reassessments and adjustment of services should be provided with all children. Additional medical, social, and/or vocational services including specialized learning programs may be necessary.Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well. | 364 | Deoxyhypusine Synthase Disorder |
nord_365_0 | Overview of Depersonalization Disorder | Depersonalization disorder is a psychiatric disorder affecting emotions and behavior. It is characterized by an alteration in how an affected individual perceives or experiences his or her unique sense of self. The usual sense of one's own reality is temporarily lost or changed. A feeling of detachment from, or being an outside observer of, one's mental processes or body occurs such as the sensation of being in a dream. | Overview of Depersonalization Disorder. Depersonalization disorder is a psychiatric disorder affecting emotions and behavior. It is characterized by an alteration in how an affected individual perceives or experiences his or her unique sense of self. The usual sense of one's own reality is temporarily lost or changed. A feeling of detachment from, or being an outside observer of, one's mental processes or body occurs such as the sensation of being in a dream. | 365 | Depersonalization Disorder |
nord_365_1 | Symptoms of Depersonalization Disorder | Depersonalization disorder is characterized by persistent or recurring episodes of the loss of the sense of self (depersonalization). The symptoms of depersonalization disorder are sufficient enough to cause marked distress or impairment in social, occupational, or other important areas of life. The usual sense of one's self or reality is temporarily changed or lost. A feeling of detachment from, or being an outside observer of, one's mental processes or body occurs. The affected individual may feel as if he/she is in a dream. Affected individuals may experience various types of lack of sensory stimulation (sensory anesthesia) and a sensation of not being in complete control of one's actions, including speech. This condition may not occur during the course of another mental disorder or be the effects of a substance or general medical condition.Depersonalization disorder usually starts during adolescence or early adulthood. The disorder is usually chronic with periods of remission. More severe manifestations may be aggravated by mild anxiety or depression. The disorder usually disappears gradually. | Symptoms of Depersonalization Disorder. Depersonalization disorder is characterized by persistent or recurring episodes of the loss of the sense of self (depersonalization). The symptoms of depersonalization disorder are sufficient enough to cause marked distress or impairment in social, occupational, or other important areas of life. The usual sense of one's self or reality is temporarily changed or lost. A feeling of detachment from, or being an outside observer of, one's mental processes or body occurs. The affected individual may feel as if he/she is in a dream. Affected individuals may experience various types of lack of sensory stimulation (sensory anesthesia) and a sensation of not being in complete control of one's actions, including speech. This condition may not occur during the course of another mental disorder or be the effects of a substance or general medical condition.Depersonalization disorder usually starts during adolescence or early adulthood. The disorder is usually chronic with periods of remission. More severe manifestations may be aggravated by mild anxiety or depression. The disorder usually disappears gradually. | 365 | Depersonalization Disorder |
nord_365_2 | Causes of Depersonalization Disorder | The exact cause of depersonalization disorder is not known. A traumatic event such as military combat, a car accident, or being a victim of a violent crime may trigger an episode of depersonalization disorder. Substance use may cause depersonalization episodes, but not the disorder. | Causes of Depersonalization Disorder. The exact cause of depersonalization disorder is not known. A traumatic event such as military combat, a car accident, or being a victim of a violent crime may trigger an episode of depersonalization disorder. Substance use may cause depersonalization episodes, but not the disorder. | 365 | Depersonalization Disorder |
nord_365_3 | Affects of Depersonalization Disorder | Depersonalization disorder is believed to affect women twice as much as men. The disorder most commonly affects individuals between the ages of 15 and 30. It is rarely seen in those over the age of 40. | Affects of Depersonalization Disorder. Depersonalization disorder is believed to affect women twice as much as men. The disorder most commonly affects individuals between the ages of 15 and 30. It is rarely seen in those over the age of 40. | 365 | Depersonalization Disorder |
nord_365_4 | Related disorders of Depersonalization Disorder | The following disorders may be associated with Depersonalization Disorder as secondary characteristics. They are not necessary for a differential diagnosis:Panic-Anxiety Syndrome (Panic Disorder) is characterized by recurrent attacks of intense fear or discomfort beginning without warning. These attacks typically begin with the sudden onset of intense apprehension, fear, terror, or discomfort without apparent cause. At least four of the following symptoms may occur: shortness of breath (dyspnea) or smothering sensations; dizziness, unsteady feelings, or faintness; choking; palpitations or accelerated heart rate; trembling or shaking; sweating; nausea or abdominal distress; loss of one's sense of self (depersonalization) or feelings of unreality; numbness or tingling sensations (paresthesias); flushes (hot flashes) or chills; chest pain or discomfort; etc. (For more information, choose “Panic-Anxiety Syndrome” as your search term in the Rare Disease Database.)Agoraphobia is the fear of being in places or situations from which escape might be difficult or embarrassing, or in which help might not be available in the event of a panic attack. As a result of this intense fear, people with Agoraphobia do not leave their home. Common situations that may trigger an agoraphobic attack include being outside the home alone, being in a crowd or standing in line, being on a bridge, or traveling in a bus, train, or car. | Related disorders of Depersonalization Disorder. The following disorders may be associated with Depersonalization Disorder as secondary characteristics. They are not necessary for a differential diagnosis:Panic-Anxiety Syndrome (Panic Disorder) is characterized by recurrent attacks of intense fear or discomfort beginning without warning. These attacks typically begin with the sudden onset of intense apprehension, fear, terror, or discomfort without apparent cause. At least four of the following symptoms may occur: shortness of breath (dyspnea) or smothering sensations; dizziness, unsteady feelings, or faintness; choking; palpitations or accelerated heart rate; trembling or shaking; sweating; nausea or abdominal distress; loss of one's sense of self (depersonalization) or feelings of unreality; numbness or tingling sensations (paresthesias); flushes (hot flashes) or chills; chest pain or discomfort; etc. (For more information, choose “Panic-Anxiety Syndrome” as your search term in the Rare Disease Database.)Agoraphobia is the fear of being in places or situations from which escape might be difficult or embarrassing, or in which help might not be available in the event of a panic attack. As a result of this intense fear, people with Agoraphobia do not leave their home. Common situations that may trigger an agoraphobic attack include being outside the home alone, being in a crowd or standing in line, being on a bridge, or traveling in a bus, train, or car. | 365 | Depersonalization Disorder |
nord_365_5 | Diagnosis of Depersonalization Disorder | The diagnosis of depersonalization disorder can be suspected after a complete physical examination and laboratory tests have ruled out any substance or geneal medical condition. A complete psychiatric evaluation should also be conducted. | Diagnosis of Depersonalization Disorder. The diagnosis of depersonalization disorder can be suspected after a complete physical examination and laboratory tests have ruled out any substance or geneal medical condition. A complete psychiatric evaluation should also be conducted. | 365 | Depersonalization Disorder |
nord_365_6 | Therapies of Depersonalization Disorder | TreatmentTreatment of depersonalization disorder involves psychotherapy. The antidepressant drug desipramine may be beneficial. The drugs dextroamphetamines and amobarbital (Amytal) combined with chlorpromazine (Thorazine) may be beneficial if anxiety is experienced. Other treatment is symptomatic and supportive. | Therapies of Depersonalization Disorder. TreatmentTreatment of depersonalization disorder involves psychotherapy. The antidepressant drug desipramine may be beneficial. The drugs dextroamphetamines and amobarbital (Amytal) combined with chlorpromazine (Thorazine) may be beneficial if anxiety is experienced. Other treatment is symptomatic and supportive. | 365 | Depersonalization Disorder |
nord_366_0 | Overview of Dercum’s Disease | Dercum's disease is a rare disorder characterized by multiple, painful growths of fatty tissue (lipomas). Fat tissue is known as loose connective tissue, hence Dercum’s disease is a loose connective tissue disease. The lipomas mainly occur on the trunk, the upper arms and upper legs and are found just below the skin (subcutaneously) but also can be found deeper in the body coupled to muscle, tendons, ligaments or bone by connective tissue. Pain associated with Dercum's disease can often be severe. Pain may be caused by lipomas pressing on nearby nerves or inflamed connective tissue, also called fascia, which is commonly associated with the lipomas. Dercum's disease mainly occurs in adults and more women are affected than men. Some affected individuals may also experience weight gain, depression, lethargy, and/or confusion. The exact cause of Dercum's disease is unknown. | Overview of Dercum’s Disease. Dercum's disease is a rare disorder characterized by multiple, painful growths of fatty tissue (lipomas). Fat tissue is known as loose connective tissue, hence Dercum’s disease is a loose connective tissue disease. The lipomas mainly occur on the trunk, the upper arms and upper legs and are found just below the skin (subcutaneously) but also can be found deeper in the body coupled to muscle, tendons, ligaments or bone by connective tissue. Pain associated with Dercum's disease can often be severe. Pain may be caused by lipomas pressing on nearby nerves or inflamed connective tissue, also called fascia, which is commonly associated with the lipomas. Dercum's disease mainly occurs in adults and more women are affected than men. Some affected individuals may also experience weight gain, depression, lethargy, and/or confusion. The exact cause of Dercum's disease is unknown. | 366 | Dercum’s Disease |
nord_366_1 | Symptoms of Dercum’s Disease | The characteristic finding of Dercum’s disease is the formation of multiple, painful growths consisting of fatty tissue (lipomas) that are found just below the surface of the skin but also deep. Lipomas in people with Dercum’s disease may be found in any part of the body, although they are rare in the head, neck, hands and feet. The trunk, upper arms and upper legs are most often affected. The lipomas can be the size of a pea or as large as a grape, plum or fist. Dercum’s disease may occur in one or more people in a family with familial multiple lipomatosis (FML Type), may occur due to angiolipomas which are known to be painful (angiolipoma type) or may occur as small diffuse (widespread) pea-sized or larger lipomas anywhere in subcutaneous fat tissue especially over the ribs and including around joints due to the presence of inflammation in the body from any cause (healing disorder type). Pain may vary from mild discomfort when a growth is pressed or touched to severe pain that is disproportionate to the physical findings; pain must be present for at least three months. Some affected individuals feel that “all fat hurts.” Pain can last for hours and may come and go or last continuously. In severe cases, pain may worsen with movement. Many people with Dercum’s disease describe exacerbations or “flares” of pain that may be accompanied by worsening of symptoms such as fatigue and “brain fog”. The exact reason for pain associated with Dercum’s disease is unknown but may occur because the lipomas press on nearby nerves or because the fascia is inflamed. The lipomas associated with Dercum’s disease have more connective tissue than non Dercum’s disease fat. Connective tissue (fascia) in fat has more pain sensors than muscle, for example, and when tight or inflamed, can cause pain as in fibromyalgia. Fibromyalgia is not uncommon in people with Dercum’s disease.Some individuals with Dercum’s may experience swelling of various areas of the body, especially the hands, but often one arm or leg may be swollen and therefore more painful. Swelling occurs for no apparent reason, though on imaging, the lymphatic system can be slow to pump in the painful limb compared to the less painful limb, or frank lymphedema may be present. The pain may disappear without treatment but any manual therapy such as massage or manual lymphatic drainage can help. Significant weight gain is a common occurrence for most individuals affected by Dercum’s disease and needs to be treated to avoid progression to pre-diabetes or diabetes.Additional symptoms may occur in individuals with Dercum’s disease including fatigue, generalized weakness, a tendency to bruise easily, headaches, irritability, and stiffness after resting, especially in the morning, gastrointestinal symptoms, palpitations and shortness of breath. An association with bouts of depression, memory or concentration problems, anxiety, and a susceptibility to infection has been noted in some cases.Additional reports in the medical literature have linked Dercum’s disease to a variety of conditions including arthritis, high blood pressure (hypertension), congestive heart failure, sleep disorders, dry eyes, and myxedema, a condition due to an underactive thyroid that is characterized by dry skin, swelling around the lips and nose, mental deterioration and infection. | Symptoms of Dercum’s Disease. The characteristic finding of Dercum’s disease is the formation of multiple, painful growths consisting of fatty tissue (lipomas) that are found just below the surface of the skin but also deep. Lipomas in people with Dercum’s disease may be found in any part of the body, although they are rare in the head, neck, hands and feet. The trunk, upper arms and upper legs are most often affected. The lipomas can be the size of a pea or as large as a grape, plum or fist. Dercum’s disease may occur in one or more people in a family with familial multiple lipomatosis (FML Type), may occur due to angiolipomas which are known to be painful (angiolipoma type) or may occur as small diffuse (widespread) pea-sized or larger lipomas anywhere in subcutaneous fat tissue especially over the ribs and including around joints due to the presence of inflammation in the body from any cause (healing disorder type). Pain may vary from mild discomfort when a growth is pressed or touched to severe pain that is disproportionate to the physical findings; pain must be present for at least three months. Some affected individuals feel that “all fat hurts.” Pain can last for hours and may come and go or last continuously. In severe cases, pain may worsen with movement. Many people with Dercum’s disease describe exacerbations or “flares” of pain that may be accompanied by worsening of symptoms such as fatigue and “brain fog”. The exact reason for pain associated with Dercum’s disease is unknown but may occur because the lipomas press on nearby nerves or because the fascia is inflamed. The lipomas associated with Dercum’s disease have more connective tissue than non Dercum’s disease fat. Connective tissue (fascia) in fat has more pain sensors than muscle, for example, and when tight or inflamed, can cause pain as in fibromyalgia. Fibromyalgia is not uncommon in people with Dercum’s disease.Some individuals with Dercum’s may experience swelling of various areas of the body, especially the hands, but often one arm or leg may be swollen and therefore more painful. Swelling occurs for no apparent reason, though on imaging, the lymphatic system can be slow to pump in the painful limb compared to the less painful limb, or frank lymphedema may be present. The pain may disappear without treatment but any manual therapy such as massage or manual lymphatic drainage can help. Significant weight gain is a common occurrence for most individuals affected by Dercum’s disease and needs to be treated to avoid progression to pre-diabetes or diabetes.Additional symptoms may occur in individuals with Dercum’s disease including fatigue, generalized weakness, a tendency to bruise easily, headaches, irritability, and stiffness after resting, especially in the morning, gastrointestinal symptoms, palpitations and shortness of breath. An association with bouts of depression, memory or concentration problems, anxiety, and a susceptibility to infection has been noted in some cases.Additional reports in the medical literature have linked Dercum’s disease to a variety of conditions including arthritis, high blood pressure (hypertension), congestive heart failure, sleep disorders, dry eyes, and myxedema, a condition due to an underactive thyroid that is characterized by dry skin, swelling around the lips and nose, mental deterioration and infection. | 366 | Dercum’s Disease |
nord_366_2 | Causes of Dercum’s Disease | The exact cause of Dercum’s disease is unknown. In most cases, Dercum’s disease appears to occur spontaneously for no apparent reason (sporadic), though causes of inflammation should be sought. One case reported the development of Dercum’s disease in a man after trauma (motor vehicle accident).Some reports in the medical literature have suggested that Dercum’s disease may be an autoimmune disorder- a disorder in which the body’s immune system mistakenly attacks healthy tissue. Disturbances in endocrine function and improper breakdown (metabolism) of fat have also been proposed as potentially playing a role the development of the disorder. One case reported in the medical literature was linked to the use of high-doses of corticosteroids and some cases have been linked to infection including Lyme disease or Valley fever (coccidioidomycosis).Some cases of Dercum’s disease have run in families and several reports in the medical literature cite the possibility that the disorder may be inherited as an autosomal dominant trait in these cases (FML type or angiolipomatosis type). Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. The altered 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 altered gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females. | Causes of Dercum’s Disease. The exact cause of Dercum’s disease is unknown. In most cases, Dercum’s disease appears to occur spontaneously for no apparent reason (sporadic), though causes of inflammation should be sought. One case reported the development of Dercum’s disease in a man after trauma (motor vehicle accident).Some reports in the medical literature have suggested that Dercum’s disease may be an autoimmune disorder- a disorder in which the body’s immune system mistakenly attacks healthy tissue. Disturbances in endocrine function and improper breakdown (metabolism) of fat have also been proposed as potentially playing a role the development of the disorder. One case reported in the medical literature was linked to the use of high-doses of corticosteroids and some cases have been linked to infection including Lyme disease or Valley fever (coccidioidomycosis).Some cases of Dercum’s disease have run in families and several reports in the medical literature cite the possibility that the disorder may be inherited as an autosomal dominant trait in these cases (FML type or angiolipomatosis type). Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. The altered 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 altered gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females. | 366 | Dercum’s Disease |
nord_366_3 | Affects of Dercum’s Disease | Dercum’s disease affects females more often than males with medical publications citing the disease as 5-30 times more common in women. Dercum’s disease can affect individuals of any age with an average age of 34 years in one medical publication. Although an extremely rare occurrence, it has been reported in children. The prevalence of Dercum’s disease is unknown. The disorder is underdiagnosed, making it difficult to determine its true frequency in the general population. Dercum’s disease was first described in the medical literature in 1882 by an American neurologist named Francis Xavier Dercum. | Affects of Dercum’s Disease. Dercum’s disease affects females more often than males with medical publications citing the disease as 5-30 times more common in women. Dercum’s disease can affect individuals of any age with an average age of 34 years in one medical publication. Although an extremely rare occurrence, it has been reported in children. The prevalence of Dercum’s disease is unknown. The disorder is underdiagnosed, making it difficult to determine its true frequency in the general population. Dercum’s disease was first described in the medical literature in 1882 by an American neurologist named Francis Xavier Dercum. | 366 | Dercum’s Disease |
nord_366_4 | Related disorders of Dercum’s Disease | Symptoms of the following disorders can be similar to those of Dercum’s disease. Comparisons may be useful for a differential diagnosis.Madelung’s disease, also known as multiple symmetric lipomatosis, is a rare disorder affecting uncoupling protein-1 and possibly brown fat tissue. Madelung’s disease results in the abnormal accumulation of fat deposits or lipomas around the neck, shoulders, upper arms and upper back. Adult male alcoholics are most often affected, although women and people who do not drink can also develop Madelung’s disease. (For more information on this disorder, choose “Madelung’s” as your search term in the Rare Disease Database.)Fibromyalgia is a chronic disorder characterized by pain throughout the muscles of the body and abnormally persistent episodes of fatigue. The pain may begin gradually or have a sudden onset. Additional symptoms may include muscle spasms and stiffness. The parts of the body most frequently affected are the back of the neck, shoulders, lower back, elbows, hips, and/or knees. In addition, small specific areas known as “tender points” are typically painful when pressure is applied to them. Some people with fibromyalgia may also experience chest pain, difficulty concentrating, headaches, painful and/or frequent urination, diarrhea, constipation, numbness of the mouth, and/or unrefreshing (non-restorative) sleep.Familial multiple lipomatosis is a rare genetic disorder characterized by the formation of multiple growths of fatty tissue (lipomas) that most often affect the trunk, arms and upper leg. The size and number of lipomas varies from person to person. Some individuals may develop hundreds of small lipomas that do not cause symptoms (asymptomatic), and are often found in similar locations on one side of the body compared to the other side (symmetric). Unlike Dercum’s disease, the lipomas do not cause pain. The neck and shoulders are usually not affected. Onset of this disorder is usually during adolescence. Familial multiple lipomatosis is inherited in an autosomal dominant pattern. One or more members of a family with familial multiple lipomatosis may go on to develop pain in the lipomas along with additional signs and symptoms consistent with Dercum’s disease.Angiolipomatosis is a rare disorder characterized by multiple lipomas with increased numbers of blood vessels that contain fibrin clots, and larger numbers of mast cells. Angiolipomas are known to be painful and hence people with angiolipomas are said to have Dercum’s disease, angiolipomatosis type. Angiolipomas may be inherited in an autosomal dominant manner.Several disorders are characterized by the development of benign (noncancerous) growths consisting of fatty tissue (lipomas) including Proteus syndrome, PTEN hamartoma syndrome, and Gardner syndrome. These disorders often have additional symptoms that can distinguish them from Dercum’s disease. (For more information on this disorder, choose the exact disorder name as your search term in the Rare Disease Database.)Lipedema is a common fat disorder in women where increased subcutaneous fat grows to excess on the limbs. Lipedema fat can also be painful especially when touched. A woman with lipedema may also have Dercum’s disease and obesity. The disproportion of a larger lower body compared to the trunk is uniquely classic for lipedema. The pain experience is very individual therefore pain cannot be used as a decisive criterion for a diagnosis of Dercum’s disease. | Related disorders of Dercum’s Disease. Symptoms of the following disorders can be similar to those of Dercum’s disease. Comparisons may be useful for a differential diagnosis.Madelung’s disease, also known as multiple symmetric lipomatosis, is a rare disorder affecting uncoupling protein-1 and possibly brown fat tissue. Madelung’s disease results in the abnormal accumulation of fat deposits or lipomas around the neck, shoulders, upper arms and upper back. Adult male alcoholics are most often affected, although women and people who do not drink can also develop Madelung’s disease. (For more information on this disorder, choose “Madelung’s” as your search term in the Rare Disease Database.)Fibromyalgia is a chronic disorder characterized by pain throughout the muscles of the body and abnormally persistent episodes of fatigue. The pain may begin gradually or have a sudden onset. Additional symptoms may include muscle spasms and stiffness. The parts of the body most frequently affected are the back of the neck, shoulders, lower back, elbows, hips, and/or knees. In addition, small specific areas known as “tender points” are typically painful when pressure is applied to them. Some people with fibromyalgia may also experience chest pain, difficulty concentrating, headaches, painful and/or frequent urination, diarrhea, constipation, numbness of the mouth, and/or unrefreshing (non-restorative) sleep.Familial multiple lipomatosis is a rare genetic disorder characterized by the formation of multiple growths of fatty tissue (lipomas) that most often affect the trunk, arms and upper leg. The size and number of lipomas varies from person to person. Some individuals may develop hundreds of small lipomas that do not cause symptoms (asymptomatic), and are often found in similar locations on one side of the body compared to the other side (symmetric). Unlike Dercum’s disease, the lipomas do not cause pain. The neck and shoulders are usually not affected. Onset of this disorder is usually during adolescence. Familial multiple lipomatosis is inherited in an autosomal dominant pattern. One or more members of a family with familial multiple lipomatosis may go on to develop pain in the lipomas along with additional signs and symptoms consistent with Dercum’s disease.Angiolipomatosis is a rare disorder characterized by multiple lipomas with increased numbers of blood vessels that contain fibrin clots, and larger numbers of mast cells. Angiolipomas are known to be painful and hence people with angiolipomas are said to have Dercum’s disease, angiolipomatosis type. Angiolipomas may be inherited in an autosomal dominant manner.Several disorders are characterized by the development of benign (noncancerous) growths consisting of fatty tissue (lipomas) including Proteus syndrome, PTEN hamartoma syndrome, and Gardner syndrome. These disorders often have additional symptoms that can distinguish them from Dercum’s disease. (For more information on this disorder, choose the exact disorder name as your search term in the Rare Disease Database.)Lipedema is a common fat disorder in women where increased subcutaneous fat grows to excess on the limbs. Lipedema fat can also be painful especially when touched. A woman with lipedema may also have Dercum’s disease and obesity. The disproportion of a larger lower body compared to the trunk is uniquely classic for lipedema. The pain experience is very individual therefore pain cannot be used as a decisive criterion for a diagnosis of Dercum’s disease. | 366 | Dercum’s Disease |
nord_366_5 | Diagnosis of Dercum’s Disease | A diagnosis of Dercum’s disease is suspected based on a detailed patient history, a thorough clinical evaluation and identification of characteristic multiple lipomas. The distribution of the lipomas is important in distinguishing Dercum’s disease from the other disorders involving lipomas. Surgical removal and microscopic study (biopsy) of affected tissue confirms that these growths are lipomas. | Diagnosis of Dercum’s Disease. A diagnosis of Dercum’s disease is suspected based on a detailed patient history, a thorough clinical evaluation and identification of characteristic multiple lipomas. The distribution of the lipomas is important in distinguishing Dercum’s disease from the other disorders involving lipomas. Surgical removal and microscopic study (biopsy) of affected tissue confirms that these growths are lipomas. | 366 | Dercum’s Disease |
nord_366_6 | Therapies of Dercum’s Disease | TreatmentNo specific treatment exists for Dercum’s disease. Treatment is directed toward the specific symptoms that are apparent in each individual and is primarily focus on easing the characteristic painful episodes.Various painkillers (analgesics) have been tried with limited effectiveness. Injections of corticosteroids have also been used to treat individuals with Dercum’s disease. However, in one reported case in the medical literature, the use of high-doses of corticosteroids was linked as a possible cause of the disease. Intravenous administration of the pain reliever lidocaine and/or ketamine may provide temporary relief from pain in some people.Surgical excision of lipomas may temporarily relieve symptoms although the generation of inflammation (part of the healing process) during and after the surgery may induce more lipomas to develop in that area. Liposuction has been used as a supportive treatment for some individuals with Dercum’s disease and may provide an initial reduction in pain and improvement in quality of life. These effects may lessen over time.Psychotherapy and consultation with pain management specialists may be helpful for enabling affected individuals to cope with long-term intense pain. Other treatment is symptomatic and supportive. | Therapies of Dercum’s Disease. TreatmentNo specific treatment exists for Dercum’s disease. Treatment is directed toward the specific symptoms that are apparent in each individual and is primarily focus on easing the characteristic painful episodes.Various painkillers (analgesics) have been tried with limited effectiveness. Injections of corticosteroids have also been used to treat individuals with Dercum’s disease. However, in one reported case in the medical literature, the use of high-doses of corticosteroids was linked as a possible cause of the disease. Intravenous administration of the pain reliever lidocaine and/or ketamine may provide temporary relief from pain in some people.Surgical excision of lipomas may temporarily relieve symptoms although the generation of inflammation (part of the healing process) during and after the surgery may induce more lipomas to develop in that area. Liposuction has been used as a supportive treatment for some individuals with Dercum’s disease and may provide an initial reduction in pain and improvement in quality of life. These effects may lessen over time.Psychotherapy and consultation with pain management specialists may be helpful for enabling affected individuals to cope with long-term intense pain. Other treatment is symptomatic and supportive. | 366 | Dercum’s Disease |
nord_367_0 | Overview of Dermatitis Herpetiformis | SummaryDermatitis herpetiformis (DH) is a rare, chronic, autoimmune skin condition characterized by the presence of groups of severely itchy blisters and raised red skin lesions. These are most commonly located on the elbows, knees, buttocks, lower back and scalp. The most common age of onset of DH is 30-40 years of age but individuals of all ages can be affected. DH is rare in children.DH is a skin manifestation of celiac disease (CD). DH is treated with a gluten free diet and frequently a medication called dapsone. | Overview of Dermatitis Herpetiformis. SummaryDermatitis herpetiformis (DH) is a rare, chronic, autoimmune skin condition characterized by the presence of groups of severely itchy blisters and raised red skin lesions. These are most commonly located on the elbows, knees, buttocks, lower back and scalp. The most common age of onset of DH is 30-40 years of age but individuals of all ages can be affected. DH is rare in children.DH is a skin manifestation of celiac disease (CD). DH is treated with a gluten free diet and frequently a medication called dapsone. | 367 | Dermatitis Herpetiformis |
nord_367_1 | Symptoms of Dermatitis Herpetiformis | This autoimmune disease may cause skin, oral and/or gastrointestinal manifestations related to gluten-sensitivity.Skin Manifestations
The classic finding of DH is the development of intensely itchy blisters, and red raised skin lesions that occur in groups. Itching and burning may be almost intolerable and the need to scratch may become irresistible. The most common sites for lesion development are the elbows, knees, buttocks, and scalp. The face and groin are less frequently involved.Oral Manifestations
Tooth enamel defects found in CD such as horizontal grooves, pits, or discoloration may occur in patients with DH. Patients with DH can rarely develop oral ulcerations (canker sores).Gastrointestinal Manifestations
DH is a skin manifestation of CD and virtually every patient has gluten sensitivity causing inflammation and damage to the small intestine. DH patients generally have less gastrointestinal symptoms than patients with CD. Symptomatic patients may present with abdominal bloating, cramping, pain, diarrhea, or constipation. | Symptoms of Dermatitis Herpetiformis. This autoimmune disease may cause skin, oral and/or gastrointestinal manifestations related to gluten-sensitivity.Skin Manifestations
The classic finding of DH is the development of intensely itchy blisters, and red raised skin lesions that occur in groups. Itching and burning may be almost intolerable and the need to scratch may become irresistible. The most common sites for lesion development are the elbows, knees, buttocks, and scalp. The face and groin are less frequently involved.Oral Manifestations
Tooth enamel defects found in CD such as horizontal grooves, pits, or discoloration may occur in patients with DH. Patients with DH can rarely develop oral ulcerations (canker sores).Gastrointestinal Manifestations
DH is a skin manifestation of CD and virtually every patient has gluten sensitivity causing inflammation and damage to the small intestine. DH patients generally have less gastrointestinal symptoms than patients with CD. Symptomatic patients may present with abdominal bloating, cramping, pain, diarrhea, or constipation. | 367 | Dermatitis Herpetiformis |
nord_367_2 | Causes of Dermatitis Herpetiformis | The cause of DH appears to be complex, involving both genetic and environmental factors. The importance of gluten in the development of DH is supported by the observation that elimination of dietary gluten can result in remission of the lesions. Genetics
A genetic contribution to DH is supported by familial studies that demonstrate that first-degree relatives of patients with DH have an increased risk for both DH and CD. The genes that have been found to be closely associated with DH are certain HLA types (HLA-DQ2 and to a lesser extent, HLA-DQ8). Environment
The main environmental factor that leads to DH is dietary gluten. | Causes of Dermatitis Herpetiformis. The cause of DH appears to be complex, involving both genetic and environmental factors. The importance of gluten in the development of DH is supported by the observation that elimination of dietary gluten can result in remission of the lesions. Genetics
A genetic contribution to DH is supported by familial studies that demonstrate that first-degree relatives of patients with DH have an increased risk for both DH and CD. The genes that have been found to be closely associated with DH are certain HLA types (HLA-DQ2 and to a lesser extent, HLA-DQ8). Environment
The main environmental factor that leads to DH is dietary gluten. | 367 | Dermatitis Herpetiformis |
nord_367_3 | Affects of Dermatitis Herpetiformis | DH most frequently occurs in individuals of northern European heritage. It is estimated that this disorder affects as many as 75.3 per 100,000 people in northern Europe. The incidence of DH appears to be decreasing, possibly due to better and earlier detection of CD (before they develop DH later in life).The reported mean age of onset is in the third or fourth decade. However, individuals of all ages can be affected. It is uncommon in children. Males have been reported to be slightly more likely to develop DH than females, but the reason for male predominance in DH is unknown. | Affects of Dermatitis Herpetiformis. DH most frequently occurs in individuals of northern European heritage. It is estimated that this disorder affects as many as 75.3 per 100,000 people in northern Europe. The incidence of DH appears to be decreasing, possibly due to better and earlier detection of CD (before they develop DH later in life).The reported mean age of onset is in the third or fourth decade. However, individuals of all ages can be affected. It is uncommon in children. Males have been reported to be slightly more likely to develop DH than females, but the reason for male predominance in DH is unknown. | 367 | Dermatitis Herpetiformis |
nord_367_4 | Related disorders of Dermatitis Herpetiformis | The differential diagnosis of DH includes many itchy and blistering disorders such as:Linear IgA disease: A rare chronic skin disease characterized by the development of groups of itchy skin blisters and raised lesions (papules) It is not associated with gluten sensitivity. Blisters and hives develop on the skin, especially on the arms, legs, lower back and/or buttocks. The skin may become very red and itchy. This is an autoimmune skin disease and is sometimes triggered by medications.Pemphigoid: An autoimmune blistering skin disorder characterized by the development of blisters of the skin and the mucous membranes of the mouth, eyes and/or genitals. This condition often starts with hives of the skin followed by tense blisters. It is more common in the elderlyEczema: A group of medical conditions that can cause the skin to become inflamed or irritated. The basic symptoms include dry skin, sore rashes, and intense itch.Scabies: An itchy, highly contagious skin disease caused by an infestation by the mite Sarcoptes scabiei. It is transmitted by direct skin-to-skin contact and is predominantly found with severe and relentless itch. It frequently involves the web spaces of the hands, axilla and groin. | Related disorders of Dermatitis Herpetiformis. The differential diagnosis of DH includes many itchy and blistering disorders such as:Linear IgA disease: A rare chronic skin disease characterized by the development of groups of itchy skin blisters and raised lesions (papules) It is not associated with gluten sensitivity. Blisters and hives develop on the skin, especially on the arms, legs, lower back and/or buttocks. The skin may become very red and itchy. This is an autoimmune skin disease and is sometimes triggered by medications.Pemphigoid: An autoimmune blistering skin disorder characterized by the development of blisters of the skin and the mucous membranes of the mouth, eyes and/or genitals. This condition often starts with hives of the skin followed by tense blisters. It is more common in the elderlyEczema: A group of medical conditions that can cause the skin to become inflamed or irritated. The basic symptoms include dry skin, sore rashes, and intense itch.Scabies: An itchy, highly contagious skin disease caused by an infestation by the mite Sarcoptes scabiei. It is transmitted by direct skin-to-skin contact and is predominantly found with severe and relentless itch. It frequently involves the web spaces of the hands, axilla and groin. | 367 | Dermatitis Herpetiformis |
nord_367_5 | Diagnosis of Dermatitis Herpetiformis | In addition to recognizing the consistent clinical findings (see signs and symptoms), diagnosis of DH can be made by performing a skin biopsy for direct immunofluorescence microscopy (DIF). The characteristic finding that is necessary is the presence of antibody protein (IgA) deposits within the dermis. These antibody protein (IgA) deposits are not normally found in skin tissue. It has been reported that DIF is positive in DH 92% of the time.Clinical Testing and Work-Up The initial approach to diagnosis of DH who present with suggestive clinical findings involves obtaining a skin biopsy of the lesion for routine staining and a perilesional skin biopsy for DIF. Blood tests (serology) are used as an adjunctive test to support the diagnosis and can also be used to monitor adherence to dietary therapy. | Diagnosis of Dermatitis Herpetiformis. In addition to recognizing the consistent clinical findings (see signs and symptoms), diagnosis of DH can be made by performing a skin biopsy for direct immunofluorescence microscopy (DIF). The characteristic finding that is necessary is the presence of antibody protein (IgA) deposits within the dermis. These antibody protein (IgA) deposits are not normally found in skin tissue. It has been reported that DIF is positive in DH 92% of the time.Clinical Testing and Work-Up The initial approach to diagnosis of DH who present with suggestive clinical findings involves obtaining a skin biopsy of the lesion for routine staining and a perilesional skin biopsy for DIF. Blood tests (serology) are used as an adjunctive test to support the diagnosis and can also be used to monitor adherence to dietary therapy. | 367 | Dermatitis Herpetiformis |
nord_367_6 | Therapies of Dermatitis Herpetiformis | Treatment
The antibiotic dapsone is usually very effective in treating this condition. Symptomatic improvement may occur in as little as several hours after the first dose. However, as it may cause side effects, treatment with dapsone requires regular monitoring by a physician and regular laboratory testing.A strict gluten-free diet is effective for both DH and the associated gastrointestinal manifestations. However, the benefits of a gluten-free diet may require several months to become noticeable. Strict adherence to a gluten-free diet may require counseling with a dietician to help identify and eliminate both obvious and hidden sources of dietary gluten, while also finding alternatives to gluten-containing foods. The preferred approach to the treatment of DH is a combination of dapsone and a strict gluten-free diet. Dapsone is initially prescribed to achieve rapid clearance of symptoms. Tapering of the dapsone dose can often be achieved if patients maintain a strict gluten free diet. Many people will require some dose of dapsone to prevent flares which are usually related to inadvertent gluten intake.For patients intolerant to dapsone, other medications may be used. The most common alternative is sulfapyridine. Topical corticosteroids may be used short-term to lessen the intensity of the itching, but do not suffice as long-term treatment. Patients are usually managed by a dermatologist (for management of DH) and a nutritionist (for dietary counseling). | Therapies of Dermatitis Herpetiformis. Treatment
The antibiotic dapsone is usually very effective in treating this condition. Symptomatic improvement may occur in as little as several hours after the first dose. However, as it may cause side effects, treatment with dapsone requires regular monitoring by a physician and regular laboratory testing.A strict gluten-free diet is effective for both DH and the associated gastrointestinal manifestations. However, the benefits of a gluten-free diet may require several months to become noticeable. Strict adherence to a gluten-free diet may require counseling with a dietician to help identify and eliminate both obvious and hidden sources of dietary gluten, while also finding alternatives to gluten-containing foods. The preferred approach to the treatment of DH is a combination of dapsone and a strict gluten-free diet. Dapsone is initially prescribed to achieve rapid clearance of symptoms. Tapering of the dapsone dose can often be achieved if patients maintain a strict gluten free diet. Many people will require some dose of dapsone to prevent flares which are usually related to inadvertent gluten intake.For patients intolerant to dapsone, other medications may be used. The most common alternative is sulfapyridine. Topical corticosteroids may be used short-term to lessen the intensity of the itching, but do not suffice as long-term treatment. Patients are usually managed by a dermatologist (for management of DH) and a nutritionist (for dietary counseling). | 367 | Dermatitis Herpetiformis |
nord_368_0 | Overview of Dermatomyositis | SummaryDermatomyositis is a type of inflammatory myopathy characterized by inflammatory and degenerative changes of the muscles and skin. Associated symptoms and physical findings may vary widely from case to case as patients may present differently. Muscle abnormalities may begin with aches and weakness of the muscles of the trunk, upper arms, hips, and thighs (proximal muscles). Muscles may be stiff, sore, tender and, eventually, show signs of degeneration (atrophy). Affected individuals may experience difficulty in performing certain functions, such as raising their arms and/or climbing stairs or develop speech and swallowing difficulties. Skin abnormalities associated with dermatomyositis often include a distinctive reddish-purple rash (heliotrope rash) on the upper eyelid or across the cheeks and bridge of the nose in a “butterfly” distribution and on the forehead and scalp. Other characteristic rashes include scaling and redness of the knuckles, elbows, knees, and/or other extensor regions (Gottron papules and sign); an abnormal accumulation of fluid (edema) in body tissues surrounding the eyes; and/or other features. The symptoms of childhood (juvenile) dermatomyositis (JDM) are similar to those associated with the adult form of the disorder. However, onset is usually more sudden. In addition, abnormal accumulations of calcium deposits (calcifications) in muscle and skin tissues as well as involvement of the digestive (gastrointestinal [GI]) tract are more common in JDM.IntroductionThe inflammatory myopathies are a group of diseases that involve chronic muscle inflammation and weakness. They are thought to be autoimmune diseases, meaning the body’s natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack perfectly healthy tissue for unknown reasons, leading to inflammation or swelling. | Overview of Dermatomyositis. SummaryDermatomyositis is a type of inflammatory myopathy characterized by inflammatory and degenerative changes of the muscles and skin. Associated symptoms and physical findings may vary widely from case to case as patients may present differently. Muscle abnormalities may begin with aches and weakness of the muscles of the trunk, upper arms, hips, and thighs (proximal muscles). Muscles may be stiff, sore, tender and, eventually, show signs of degeneration (atrophy). Affected individuals may experience difficulty in performing certain functions, such as raising their arms and/or climbing stairs or develop speech and swallowing difficulties. Skin abnormalities associated with dermatomyositis often include a distinctive reddish-purple rash (heliotrope rash) on the upper eyelid or across the cheeks and bridge of the nose in a “butterfly” distribution and on the forehead and scalp. Other characteristic rashes include scaling and redness of the knuckles, elbows, knees, and/or other extensor regions (Gottron papules and sign); an abnormal accumulation of fluid (edema) in body tissues surrounding the eyes; and/or other features. The symptoms of childhood (juvenile) dermatomyositis (JDM) are similar to those associated with the adult form of the disorder. However, onset is usually more sudden. In addition, abnormal accumulations of calcium deposits (calcifications) in muscle and skin tissues as well as involvement of the digestive (gastrointestinal [GI]) tract are more common in JDM.IntroductionThe inflammatory myopathies are a group of diseases that involve chronic muscle inflammation and weakness. They are thought to be autoimmune diseases, meaning the body’s natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack perfectly healthy tissue for unknown reasons, leading to inflammation or swelling. | 368 | Dermatomyositis |
nord_368_1 | Symptoms of Dermatomyositis | In those with dermatomyositis, the onset of symptoms may be gradual (insidious) or sudden (acute). The symptoms often wax and wane for no apparent reason.The major symptom of the disorder is muscle weakness, most often affecting the trunk and muscles closest to the trunk (i.e., proximal muscles), such as the hips, thighs, shoulders, upper arms, and neck. The affected muscles may be stiff, sore, and/or tender and, eventually, may show signs of degeneration and muscle wasting (atrophy). Muscle weakness and degeneration progress and may lead to an awkward manner of walking (gait) and a gradual inability to perform certain tasks, such as lifting the arms, climbing steps, or dressing. Characteristic signs may include an inability to raise the head from the pillow when lying down or to rise unassisted from the floor. In some people with the disorder, involvement of muscles of the neck, tongue, and/or throat may eventually result in difficulties swallowing (dysphagia) and/or articulating speech (dysphonia). In rare cases, weakening of muscles of the chest wall and diaphragm may cause respiratory difficulties, potentially leading to life-threatening complications without prompt, appropriate treatment. In addition, in some with chronic, long-term disease, certain joints may become fixed in a permanently bent (flexed) position (contractures) and lead to problems in walking.Individuals with dermatomyositis also develop characteristic skin changes that, in some cases, may precede muscle weakness. These characteristic skin changes may be the only sign of dermatomyositis at the start in up to 40% of people. Skin abnormalities often include a distinctive reddish-purple or lilac (i.e., heliotrope) rash that may be present on the upper eyelids (heliotrope eyelids); the forehead; the cheeks and bridge of the nose (“butterfly rash”); and/or other regions. In addition, affected skin on the extensor surfaces of certain joints, such as the knuckles, elbows, knees, or other regions, may tend to become scaly, with central areas of tissue loss (atrophy) that lack or have increased pigmentation (Gottron sign). A “dusky” reddish (erythematous) rash may also develop on the upper arms, upper legs, and upper trunk. The rash tends to be itchy and can lead to trouble sleeping for many people. Although the skin rashes frequently fade completely, they may be followed by brownish discolorations (hyperpigmentation) of the skin, atrophy, scarring, and/or loss of color (depigmentation) of patches of skin (vitiligo). Dermatomyositis may also be associated with distinctive changes of the nails that can include: bluish-red, scaling lesions around the base of the nails; reddish “shininess” of the nail folds; abnormal widening (dilation) of capillaries of the nailbeds; or other findings. Additional skin manifestations may include an abnormal accumulation of fluid in body tissues (edema) surrounding the eyes (periorbital area) and in other facial regions; an increased sensitivity to light (photosensitivity); and/or other findings. In some cases of long-term chronic disease, atrophic changes may result in binding of skin to underlying tissue structures. Some affected individuals, particularly children, may also have abnormal accumulations of calcium deposits (calcinosis) in affected muscles and tissues under the skin (subcutaneous tissues), potentially leading to contractures and localized muscle atrophy. Itching and scaling lesions may develop on the scalp leading to significant hair loss.Some individuals with dermatomyositis may also develop symptoms such as low-grade fever, a general feeling of ill health (malaise), shortness of breath (dyspnea), pain in multiple joints (polyarthralgia), weight loss, and/or other abnormalities. In some cases, affected individuals, particularly those who have muscle inflammation (myositis) in association with other connective tissue disorders, experience Raynaud phenomenon. This is a condition in which sudden contraction of blood vessels supplying the fingers and toes (digits) causes a temporary interruption of blood flow and associated numbness, tingling, abnormal discoloration of the digits, and pain. Episodes are most commonly triggered by exposure to cold temperatures. (For more information, choose “Raynaud” as your search term in the Rare Disease Database).Muscle weakness and impairment may progress to affect other areas of the body, including muscles of the GI tract, within the cardiovascular system (i.e., heart, blood vessels, and blood circulation), and/or the lungs. In rare cases the heart muscle may weaken (cardiomyopathy) or irregularity of the heartbeat can occur (arrhythmias). Inflammation of the lung tissue (interstitial pneumonitis or interstitial lung disease) can result in breathing difficulties (dyspnea) and coughing. Some studies have shown plaque accumulation in the arteries (atherosclerosis) in people with dermatomyositis.Furthermore, in some individuals with dermatomyositis, there may be an association with an underlying cancer (malignancy). Reports indicate that the malignancy may precede, occur in association with, or develop subsequent to the onset of dermatomyositis. Malignancy-associated dermatomyositis appears to occur more frequently in individuals over the age 40-50. Although there is no characteristic cancer site or type, experts indicate that underlying malignancies most commonly arise in the GI tract, lungs, breast, ovary, testis, or certain white blood cells (lymphocytes) or lymphoid tissue (i.e., certain lymphomas and leukemias, multiple myeloma). The relationship between dermatomyositis and malignancies is not fully understood.The symptoms and physical findings associated with childhood dermatomyositis are similar to those observed in adult dermatomyositis. Onset is usually more sudden (acute) than in the adult form and often involves skin manifestations followed by muscle weakness. Calcification of muscles and tissues is more frequent and widespread in childhood dermatomyositis as compared to adult forms. The deposits have a high calcium content and tend to be firm, white, or flesh-colored nodules over bony areas which can include the elbows, knees, and extremities. These calcifications often develop within three years of diagnosis but may develop up to 20 years later. Affected children also tend to have widespread inflammation of blood vessels (vasculitis), with more frequent involvement of the GI tract. In those with GI vasculitis, associated findings may include abdominal pain; difficult, infrequent, or incomplete passing of stools (constipation); or the passage of tarry, black stools (melena) or vomiting of blood due to the development of sores or eroded areas in the lining of the GI tract (bleeding peptic ulcers). Children may also develop a tiptoe gait secondary to a stiffening of the ankles. Malignancy is rarely associated with the childhood form of dermatomyositis.In rare cases known as dermatomyositis sine myositis, the skin abnormalities associated with dermatomyositis may occur without the associated muscle abnormalities. | Symptoms of Dermatomyositis. In those with dermatomyositis, the onset of symptoms may be gradual (insidious) or sudden (acute). The symptoms often wax and wane for no apparent reason.The major symptom of the disorder is muscle weakness, most often affecting the trunk and muscles closest to the trunk (i.e., proximal muscles), such as the hips, thighs, shoulders, upper arms, and neck. The affected muscles may be stiff, sore, and/or tender and, eventually, may show signs of degeneration and muscle wasting (atrophy). Muscle weakness and degeneration progress and may lead to an awkward manner of walking (gait) and a gradual inability to perform certain tasks, such as lifting the arms, climbing steps, or dressing. Characteristic signs may include an inability to raise the head from the pillow when lying down or to rise unassisted from the floor. In some people with the disorder, involvement of muscles of the neck, tongue, and/or throat may eventually result in difficulties swallowing (dysphagia) and/or articulating speech (dysphonia). In rare cases, weakening of muscles of the chest wall and diaphragm may cause respiratory difficulties, potentially leading to life-threatening complications without prompt, appropriate treatment. In addition, in some with chronic, long-term disease, certain joints may become fixed in a permanently bent (flexed) position (contractures) and lead to problems in walking.Individuals with dermatomyositis also develop characteristic skin changes that, in some cases, may precede muscle weakness. These characteristic skin changes may be the only sign of dermatomyositis at the start in up to 40% of people. Skin abnormalities often include a distinctive reddish-purple or lilac (i.e., heliotrope) rash that may be present on the upper eyelids (heliotrope eyelids); the forehead; the cheeks and bridge of the nose (“butterfly rash”); and/or other regions. In addition, affected skin on the extensor surfaces of certain joints, such as the knuckles, elbows, knees, or other regions, may tend to become scaly, with central areas of tissue loss (atrophy) that lack or have increased pigmentation (Gottron sign). A “dusky” reddish (erythematous) rash may also develop on the upper arms, upper legs, and upper trunk. The rash tends to be itchy and can lead to trouble sleeping for many people. Although the skin rashes frequently fade completely, they may be followed by brownish discolorations (hyperpigmentation) of the skin, atrophy, scarring, and/or loss of color (depigmentation) of patches of skin (vitiligo). Dermatomyositis may also be associated with distinctive changes of the nails that can include: bluish-red, scaling lesions around the base of the nails; reddish “shininess” of the nail folds; abnormal widening (dilation) of capillaries of the nailbeds; or other findings. Additional skin manifestations may include an abnormal accumulation of fluid in body tissues (edema) surrounding the eyes (periorbital area) and in other facial regions; an increased sensitivity to light (photosensitivity); and/or other findings. In some cases of long-term chronic disease, atrophic changes may result in binding of skin to underlying tissue structures. Some affected individuals, particularly children, may also have abnormal accumulations of calcium deposits (calcinosis) in affected muscles and tissues under the skin (subcutaneous tissues), potentially leading to contractures and localized muscle atrophy. Itching and scaling lesions may develop on the scalp leading to significant hair loss.Some individuals with dermatomyositis may also develop symptoms such as low-grade fever, a general feeling of ill health (malaise), shortness of breath (dyspnea), pain in multiple joints (polyarthralgia), weight loss, and/or other abnormalities. In some cases, affected individuals, particularly those who have muscle inflammation (myositis) in association with other connective tissue disorders, experience Raynaud phenomenon. This is a condition in which sudden contraction of blood vessels supplying the fingers and toes (digits) causes a temporary interruption of blood flow and associated numbness, tingling, abnormal discoloration of the digits, and pain. Episodes are most commonly triggered by exposure to cold temperatures. (For more information, choose “Raynaud” as your search term in the Rare Disease Database).Muscle weakness and impairment may progress to affect other areas of the body, including muscles of the GI tract, within the cardiovascular system (i.e., heart, blood vessels, and blood circulation), and/or the lungs. In rare cases the heart muscle may weaken (cardiomyopathy) or irregularity of the heartbeat can occur (arrhythmias). Inflammation of the lung tissue (interstitial pneumonitis or interstitial lung disease) can result in breathing difficulties (dyspnea) and coughing. Some studies have shown plaque accumulation in the arteries (atherosclerosis) in people with dermatomyositis.Furthermore, in some individuals with dermatomyositis, there may be an association with an underlying cancer (malignancy). Reports indicate that the malignancy may precede, occur in association with, or develop subsequent to the onset of dermatomyositis. Malignancy-associated dermatomyositis appears to occur more frequently in individuals over the age 40-50. Although there is no characteristic cancer site or type, experts indicate that underlying malignancies most commonly arise in the GI tract, lungs, breast, ovary, testis, or certain white blood cells (lymphocytes) or lymphoid tissue (i.e., certain lymphomas and leukemias, multiple myeloma). The relationship between dermatomyositis and malignancies is not fully understood.The symptoms and physical findings associated with childhood dermatomyositis are similar to those observed in adult dermatomyositis. Onset is usually more sudden (acute) than in the adult form and often involves skin manifestations followed by muscle weakness. Calcification of muscles and tissues is more frequent and widespread in childhood dermatomyositis as compared to adult forms. The deposits have a high calcium content and tend to be firm, white, or flesh-colored nodules over bony areas which can include the elbows, knees, and extremities. These calcifications often develop within three years of diagnosis but may develop up to 20 years later. Affected children also tend to have widespread inflammation of blood vessels (vasculitis), with more frequent involvement of the GI tract. In those with GI vasculitis, associated findings may include abdominal pain; difficult, infrequent, or incomplete passing of stools (constipation); or the passage of tarry, black stools (melena) or vomiting of blood due to the development of sores or eroded areas in the lining of the GI tract (bleeding peptic ulcers). Children may also develop a tiptoe gait secondary to a stiffening of the ankles. Malignancy is rarely associated with the childhood form of dermatomyositis.In rare cases known as dermatomyositis sine myositis, the skin abnormalities associated with dermatomyositis may occur without the associated muscle abnormalities. | 368 | Dermatomyositis |
nord_368_2 | Causes of Dermatomyositis | The specific underlying cause(s) of dermatomyositis remain unknown. However, evidence suggests that genetic, immune, and environmental factors play some role. Underlying genetic and immune mechanisms may be suggested by various findings, including an increased frequency of certain genetically determined HLAs or “human leukocyte antigens” in individuals with the disorder. HLAs are proteins that play an important role in the body’s immune system, influence the outcome of transplantation, and appear to affect an individual’s predisposition to certain diseases. Evidence suggests that certain HLAs have an increased frequency in children and adults with dermatomyositis. However, the specific implications of such findings are not fully understood.Dermatomyositis is thought to belong to a group of disorders in which the body’s natural immune defenses inappropriately act against the body’s own tissues (autoimmune disorders). In dermatomyositis, an abnormal immune reaction appears to lead to obstructive inflammatory changes of blood vessels within muscle, connective tissues of the skin, and other tissues; patchy degeneration, wasting (atrophy), and regeneration of muscle fibers; thinning of the outermost skin layer (epidermis); and/or other associated findings.Reports indicate that certain infectious agents (i.e. coxsackie virus, parvovirus, echovirus, HIV, human T-cell lymphotrophic virus Type 1, and Toxoplasma and Borrelia species) have been suggested as potential triggers for dermatomyositis. Some researchers suggest that, in genetically predisposed individuals, the presence of foreign viral proteins (antigens) that are similar to some of the body’s own proteins may trigger the production of antibodies that improperly “cross-react” or act against the body’s own cells (i.e., intramuscular blood vessels), leading to the inflammatory changes and muscle tissue damage seen in dermatomyositis. Environmental factors have also been seen to play a role in cases of juvenile dermatomyositis that develop/exacerbate in the months of April and May. In addition, researchers indicate that the association of dermatomyositis with underlying malignancies in some adults may suggest an abnormal autoimmune response directed against a common antigen in muscle and the cancerous tumor. There have also been some reports in which dermatomyositis has appeared to occur following certain vaccinations or the use of particular medications (i.e., penicillamine, the statins, quinidine, and phenylbutazone). Dermatomyositis may be initiated or exacerbated following silicone breast implants or collagen injections. However, the implications of such findings remain unknown and more data is required to establish the association. | Causes of Dermatomyositis. The specific underlying cause(s) of dermatomyositis remain unknown. However, evidence suggests that genetic, immune, and environmental factors play some role. Underlying genetic and immune mechanisms may be suggested by various findings, including an increased frequency of certain genetically determined HLAs or “human leukocyte antigens” in individuals with the disorder. HLAs are proteins that play an important role in the body’s immune system, influence the outcome of transplantation, and appear to affect an individual’s predisposition to certain diseases. Evidence suggests that certain HLAs have an increased frequency in children and adults with dermatomyositis. However, the specific implications of such findings are not fully understood.Dermatomyositis is thought to belong to a group of disorders in which the body’s natural immune defenses inappropriately act against the body’s own tissues (autoimmune disorders). In dermatomyositis, an abnormal immune reaction appears to lead to obstructive inflammatory changes of blood vessels within muscle, connective tissues of the skin, and other tissues; patchy degeneration, wasting (atrophy), and regeneration of muscle fibers; thinning of the outermost skin layer (epidermis); and/or other associated findings.Reports indicate that certain infectious agents (i.e. coxsackie virus, parvovirus, echovirus, HIV, human T-cell lymphotrophic virus Type 1, and Toxoplasma and Borrelia species) have been suggested as potential triggers for dermatomyositis. Some researchers suggest that, in genetically predisposed individuals, the presence of foreign viral proteins (antigens) that are similar to some of the body’s own proteins may trigger the production of antibodies that improperly “cross-react” or act against the body’s own cells (i.e., intramuscular blood vessels), leading to the inflammatory changes and muscle tissue damage seen in dermatomyositis. Environmental factors have also been seen to play a role in cases of juvenile dermatomyositis that develop/exacerbate in the months of April and May. In addition, researchers indicate that the association of dermatomyositis with underlying malignancies in some adults may suggest an abnormal autoimmune response directed against a common antigen in muscle and the cancerous tumor. There have also been some reports in which dermatomyositis has appeared to occur following certain vaccinations or the use of particular medications (i.e., penicillamine, the statins, quinidine, and phenylbutazone). Dermatomyositis may be initiated or exacerbated following silicone breast implants or collagen injections. However, the implications of such findings remain unknown and more data is required to establish the association. | 368 | Dermatomyositis |
nord_368_3 | Affects of Dermatomyositis | Dermatomyositis may occur at any time from infancy through approximately age 80, but most commonly it occurs between ages 40 to 60. The estimated incidence of dermatomyositis is 9.63 cases per million people. In children, the symptoms usually appear between the ages of five to 15 years. Approximately three in 1,000,000 children are affected by juvenile dermatomyositis. Females are affected by dermatomyositis twice as often as males. | Affects of Dermatomyositis. Dermatomyositis may occur at any time from infancy through approximately age 80, but most commonly it occurs between ages 40 to 60. The estimated incidence of dermatomyositis is 9.63 cases per million people. In children, the symptoms usually appear between the ages of five to 15 years. Approximately three in 1,000,000 children are affected by juvenile dermatomyositis. Females are affected by dermatomyositis twice as often as males. | 368 | Dermatomyositis |
nord_368_4 | Related disorders of Dermatomyositis | Symptoms of the following disorders may be similar to those of dermatomyositis. Comparisons may be useful for a differential diagnosis:Polymyositis is a type of inflammatory myopathy characterized by inflammatory and degenerative changes in the muscles, leading to symmetric weakness and some degree of muscle wasting (atrophy). The areas principally affected include the muscles closest to and within the trunk of the body such as the hip, shoulders, arms, pharynx and neck. Polymyositis occurs most often in women over 20 years of age, but men can also be affected. Muscle weakness usually happens over days, weeks or months. Some affected people have muscle pain, breathing problems, and trouble swallowing. (For more information, choose “polymyositis” as your search term in the Rare Disease Database.)Inclusion body myositis is a rare progressive disorder with some similar features compared to polymyositis. However, disease onset usually occurs at a later age. In addition, there is typically early, significant involvement of muscles that bend (flex) joints of the fingers and forearms and extend muscles of the legs. Muscle biopsy (see below) may reveal infiltration by certain inflammatory cells, characteristic “rimmed” cavities (vacuoles) within certain muscle fibers, necrosis, and regeneration of muscle fibers. Inclusion body myositis may also result from autoimmune dysfunction but the evidence supporting this is less than that seen with polymyositis. (For further information, choose “inclusion body” as your search term in the Rare Disease Database.)Scleroderma is a rare connective tissue disorder characterized by abnormally increased production and accumulation of collagen, the body’s major structural protein, in skin and other organs of the body. There are systemic and localized forms of scleroderma. Systemic sclerosis is characterized by hardening (induration) and thickening of the skin and abnormal degenerative changes and formation of fibrous tissue (fibrosis) in certain organs of the body including the lungs, heart, kidneys, and GI tract. Associated symptoms, which may vary widely from case to case, may include abnormal discoloration of and pain affecting the fingers and toes upon exposure to cold temperatures (Raynaud’s phenomenon); abnormal tightness, thickening, “waxiness,” and loss of elasticity of the skin; shortness of breath; difficulty swallowing; muscle weakness; joint pain; heart abnormalities including irregular heartbeats (palpitations); kidney (renal) abnormalities; and/or other symptoms and findings. In individuals with localized scleroderma, involvement is restricted to the skin, tissue under the skin (subcutaneous tissue), and, in some cases, underlying muscle and bone. Linear scleroderma is a localized form of scleroderma that may involve only certain areas of the body, such as an arm, a leg, or a portion of the face. It is characterized by multiple lesions of the skin, abnormally increased or decreased skin pigmentation (hyper or hypopigmentation), and associated atrophy of the skin, subcutaneous tissue, muscle, and bone. Although the exact cause of scleroderma is unknown, researchers suggest that the disorder also has an autoimmune cause. (For further information, choose “scleroderma” as your search term in the Rare Disease Database.)Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease of connective tissue that may affect multiple organ systems and tissues, such as the skin, joints, membranes lining the walls of certain body cavities, the kidneys, and/or the nervous system. The disorder is thought to result from an abnormal response in which the body’s immune system improperly acts against its own cells and tissues, leading to inflammation and malfunction of various organ systems. The range and severity of associated symptoms and findings may vary from case to case. However, many affected individuals may initially develop generalized symptoms, such as excessive fatigue, fever, a general feeling of ill health (malaise), loss of appetite (anorexia), weight loss, and joint swelling, inflammation, and pain. The disorder may also be associated with skin abnormalities, such as a scaling, reddish rash in a “butterfly” pattern across the cheeks and the nasal bridge; increased sensitivity to light (photosensitivity); reddish swelling around the nails; tender, reddish-purplish skin swellings; or other findings. Additional abnormalities may include muscle inflammation (myositis); spasms of small blood vessels supplying the fingers and toes in response to cold (Raynaud’s phenomenon); inflammation of the filtering units of the kidneys (nephrons); neurologic symptoms, such as headaches, seizures, and/or personality changes; and/or inflammatory changes of the membranes lining the chest cavity and lungs, lining the abdominal wall and organs, and/or surrounding the heart. Disease progression may also affect other tissues, leading to additional symptoms and findings. | Related disorders of Dermatomyositis. Symptoms of the following disorders may be similar to those of dermatomyositis. Comparisons may be useful for a differential diagnosis:Polymyositis is a type of inflammatory myopathy characterized by inflammatory and degenerative changes in the muscles, leading to symmetric weakness and some degree of muscle wasting (atrophy). The areas principally affected include the muscles closest to and within the trunk of the body such as the hip, shoulders, arms, pharynx and neck. Polymyositis occurs most often in women over 20 years of age, but men can also be affected. Muscle weakness usually happens over days, weeks or months. Some affected people have muscle pain, breathing problems, and trouble swallowing. (For more information, choose “polymyositis” as your search term in the Rare Disease Database.)Inclusion body myositis is a rare progressive disorder with some similar features compared to polymyositis. However, disease onset usually occurs at a later age. In addition, there is typically early, significant involvement of muscles that bend (flex) joints of the fingers and forearms and extend muscles of the legs. Muscle biopsy (see below) may reveal infiltration by certain inflammatory cells, characteristic “rimmed” cavities (vacuoles) within certain muscle fibers, necrosis, and regeneration of muscle fibers. Inclusion body myositis may also result from autoimmune dysfunction but the evidence supporting this is less than that seen with polymyositis. (For further information, choose “inclusion body” as your search term in the Rare Disease Database.)Scleroderma is a rare connective tissue disorder characterized by abnormally increased production and accumulation of collagen, the body’s major structural protein, in skin and other organs of the body. There are systemic and localized forms of scleroderma. Systemic sclerosis is characterized by hardening (induration) and thickening of the skin and abnormal degenerative changes and formation of fibrous tissue (fibrosis) in certain organs of the body including the lungs, heart, kidneys, and GI tract. Associated symptoms, which may vary widely from case to case, may include abnormal discoloration of and pain affecting the fingers and toes upon exposure to cold temperatures (Raynaud’s phenomenon); abnormal tightness, thickening, “waxiness,” and loss of elasticity of the skin; shortness of breath; difficulty swallowing; muscle weakness; joint pain; heart abnormalities including irregular heartbeats (palpitations); kidney (renal) abnormalities; and/or other symptoms and findings. In individuals with localized scleroderma, involvement is restricted to the skin, tissue under the skin (subcutaneous tissue), and, in some cases, underlying muscle and bone. Linear scleroderma is a localized form of scleroderma that may involve only certain areas of the body, such as an arm, a leg, or a portion of the face. It is characterized by multiple lesions of the skin, abnormally increased or decreased skin pigmentation (hyper or hypopigmentation), and associated atrophy of the skin, subcutaneous tissue, muscle, and bone. Although the exact cause of scleroderma is unknown, researchers suggest that the disorder also has an autoimmune cause. (For further information, choose “scleroderma” as your search term in the Rare Disease Database.)Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease of connective tissue that may affect multiple organ systems and tissues, such as the skin, joints, membranes lining the walls of certain body cavities, the kidneys, and/or the nervous system. The disorder is thought to result from an abnormal response in which the body’s immune system improperly acts against its own cells and tissues, leading to inflammation and malfunction of various organ systems. The range and severity of associated symptoms and findings may vary from case to case. However, many affected individuals may initially develop generalized symptoms, such as excessive fatigue, fever, a general feeling of ill health (malaise), loss of appetite (anorexia), weight loss, and joint swelling, inflammation, and pain. The disorder may also be associated with skin abnormalities, such as a scaling, reddish rash in a “butterfly” pattern across the cheeks and the nasal bridge; increased sensitivity to light (photosensitivity); reddish swelling around the nails; tender, reddish-purplish skin swellings; or other findings. Additional abnormalities may include muscle inflammation (myositis); spasms of small blood vessels supplying the fingers and toes in response to cold (Raynaud’s phenomenon); inflammation of the filtering units of the kidneys (nephrons); neurologic symptoms, such as headaches, seizures, and/or personality changes; and/or inflammatory changes of the membranes lining the chest cavity and lungs, lining the abdominal wall and organs, and/or surrounding the heart. Disease progression may also affect other tissues, leading to additional symptoms and findings. | 368 | Dermatomyositis |
nord_368_5 | Diagnosis of Dermatomyositis | Dermatomyositis may be diagnosed based upon a detailed patient history, thorough clinical examination, detection of characteristic physical findings, and certain specialized tests. Diagnostic findings include the presence of the characteristic skin rash; progressive weakness of proximal muscles; elevated levels of certain muscle enzymes (i.e., creatine kinase [CK], aldolase, aspartate aminotransferase, lactic dehydrogenase) in the liquid portion of the blood (serum) that may be suggestive of muscle inflammation; and abnormal findings on electromyography (EMG). EMG is a test that records electrical activity in skeletal (voluntary) muscles at rest and during muscle contraction. In some instances, physicians may also recommend magnetic resonance imaging (MRI), during which a magnetic field and radio waves create detailed cross-sectional images of certain tissues. In addition, muscle biopsies may sometimes be recommended to help detect certain changes that may help confirm the diagnosis. Muscle biopsy involves the removal and microscopic examination of small samples of muscle tissue. (Experts indicate that muscles recently tested with EMG should be avoided since EMG procedures may cause inflammatory changes potentially leading to false positive results upon biopsy.) Additional imaging studies may be performed to aid in the diagnosis and can include: computed tomography (CT) scanning, chest radiography, barium swallow, and ultrasound of the muscles affected.Although the results of certain blood tests may provide helpful information suggestive of the diagnosis, such findings may be nonspecific, meaning that they may be associated with a variety of autoimmune connective tissue disorders. For example, some affected individuals may have an elevated erythrocyte sedimentation rate (ESR). ESR measures the rate that red blood cells (erythrocytes) settle to the bottom of a test tube. Because erythrocytes tend to clump together and thus settle more quickly when inflammation is present, an elevated ESR functions as a nonspecific indicator of inflammation. In some affected individuals, testing may also reveal certain antinuclear antibodies (ANAs), which are “self-antibodies” (autoantibodies) that react with antigens in the nuclei of cells. A number of specific autoantibodies or myositis-specific antibodies have been identified that may be seen in some individuals with inflammatory muscle diseases, including dermatomyositis and polymyositis, that may be helpful in classifying the disease in certain cases (i.e., anti-Jo-1 antibodies, often seen in associated lung involvement).In some cases, additional tests may also be recommended to help detect or characterize certain abnormalities that may be associated with the disorder. For example, x-ray imaging may reveal calcifications in certain soft tissues. In addition, stool samples may be taken to detect blood, a finding suggestive of gastrointestinal involvement. Pulmonary function studies may also be conducted to assess for lung involvement.For adults with dermatomyositis, the possibility of an underlying malignancy should be considered during basic clinical assessment. In addition to a basic, thorough physical examination, including breast, gynecologic, and/or rectal examination, screening may include routine blood testing, analysis of urine and stool, chest x-rays, mammograms in women, and/or other tests, as well as appropriate follow-up testing as required.Diagnosis of juvenile dermatomyositis is traditionally based on the presence of the following criteria: characteristic skin rash; generalized muscle weakness; elevated muscle enzymes; myopathic changes on electromyography; and/or abnormal muscle biopsy findings. | Diagnosis of Dermatomyositis. Dermatomyositis may be diagnosed based upon a detailed patient history, thorough clinical examination, detection of characteristic physical findings, and certain specialized tests. Diagnostic findings include the presence of the characteristic skin rash; progressive weakness of proximal muscles; elevated levels of certain muscle enzymes (i.e., creatine kinase [CK], aldolase, aspartate aminotransferase, lactic dehydrogenase) in the liquid portion of the blood (serum) that may be suggestive of muscle inflammation; and abnormal findings on electromyography (EMG). EMG is a test that records electrical activity in skeletal (voluntary) muscles at rest and during muscle contraction. In some instances, physicians may also recommend magnetic resonance imaging (MRI), during which a magnetic field and radio waves create detailed cross-sectional images of certain tissues. In addition, muscle biopsies may sometimes be recommended to help detect certain changes that may help confirm the diagnosis. Muscle biopsy involves the removal and microscopic examination of small samples of muscle tissue. (Experts indicate that muscles recently tested with EMG should be avoided since EMG procedures may cause inflammatory changes potentially leading to false positive results upon biopsy.) Additional imaging studies may be performed to aid in the diagnosis and can include: computed tomography (CT) scanning, chest radiography, barium swallow, and ultrasound of the muscles affected.Although the results of certain blood tests may provide helpful information suggestive of the diagnosis, such findings may be nonspecific, meaning that they may be associated with a variety of autoimmune connective tissue disorders. For example, some affected individuals may have an elevated erythrocyte sedimentation rate (ESR). ESR measures the rate that red blood cells (erythrocytes) settle to the bottom of a test tube. Because erythrocytes tend to clump together and thus settle more quickly when inflammation is present, an elevated ESR functions as a nonspecific indicator of inflammation. In some affected individuals, testing may also reveal certain antinuclear antibodies (ANAs), which are “self-antibodies” (autoantibodies) that react with antigens in the nuclei of cells. A number of specific autoantibodies or myositis-specific antibodies have been identified that may be seen in some individuals with inflammatory muscle diseases, including dermatomyositis and polymyositis, that may be helpful in classifying the disease in certain cases (i.e., anti-Jo-1 antibodies, often seen in associated lung involvement).In some cases, additional tests may also be recommended to help detect or characterize certain abnormalities that may be associated with the disorder. For example, x-ray imaging may reveal calcifications in certain soft tissues. In addition, stool samples may be taken to detect blood, a finding suggestive of gastrointestinal involvement. Pulmonary function studies may also be conducted to assess for lung involvement.For adults with dermatomyositis, the possibility of an underlying malignancy should be considered during basic clinical assessment. In addition to a basic, thorough physical examination, including breast, gynecologic, and/or rectal examination, screening may include routine blood testing, analysis of urine and stool, chest x-rays, mammograms in women, and/or other tests, as well as appropriate follow-up testing as required.Diagnosis of juvenile dermatomyositis is traditionally based on the presence of the following criteria: characteristic skin rash; generalized muscle weakness; elevated muscle enzymes; myopathic changes on electromyography; and/or abnormal muscle biopsy findings. | 368 | Dermatomyositis |
nord_368_6 | Therapies of Dermatomyositis | Treatment
The treatment of dermatomyositis is directed toward the specific symptoms that are apparent in each individual and thus can vary from one patient to another. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians or internists; physicians who specialize in the diagnosis and treatment of connective tissue disorders (rheumatologists); specialists in the functioning of the immune system (immunologists); and/or other health care professionals. In general, treatment for the muscle involvement associated with dermatomyositis requires the use of glucocorticoids. Treatment for the skin findings associated with dermatomyositis includes: sun avoidance, sunscreens, topical glucocorticoids, anti-malarial agents, methotrexate, mycophenolate mofetil, and/or intravenous immunoglobulin (IVIg).Glucocorticoids, particularly prednisone, are widely used in the treatment of dermatomyositis and are often used first-line. Such medications, which are similar to the natural hormones produced by the outer region of the adrenal glands (adrenal cortex), are often used to reduce inflammation and associated swelling and also serve to suppress immune responses (immunosuppressive therapy). Blood levels of muscle enzyme (i.e., CK) activity are repeatedly measured to help monitor the effectiveness of such therapy. Reduction of these enzymes toward or reaching normal levels is noted in most affected adults within approximately six to 12 weeks after treatment is started, with subsequent improvement in muscle strength. When normal enzyme levels have been achieved, the dose of prednisone is usually slowly reduced (tapered). Dose levels are increased if muscle enzyme levels rise. Physicians may attempt to carefully, gradually withdraw such therapy periodically to determine whether the disease remains clinically active. In many cases, however, prolonged maintenance therapy with prednisone may be necessary. Yet reports indicate that some adults may appear to achieve a complete response. In such instances, therapy may be gradually withdrawn with careful ongoing monitoring.Affected children may initially require high dose therapy with prednisone, which often results in a return of muscle enzyme levels toward normal levels within about one to two weeks. As with adults, decreased muscle inflammation and improved muscle strength typically follow. Dose levels may then be slowly reduced to the lowest possible dose sufficient to maintain normal enzyme levels and improve symptoms. Generally, according to experts, children with dermatomyositis may be able to discontinue prednisone after approximately two years, experiencing an apparent cessation of symptoms (i.e., remission).High dose glucocorticoid therapy may produce adverse side effects, particularly after prolonged use, such as a decrease in bone density, causing bones to become brittle and weakened (osteoporosis); increasing, “superimposed” muscle weakness due to effects of the medication (i.e., corticosteroid myopathy); tissue swelling (edema); peptic ulcers; elevated blood pressure; elevated blood sugar levels; weight gain with fat deposits in the abdomen, face, and/or back of the neck or other findings. Physicians may recommend certain measures to help prevent or minimize adverse effects, such as appropriate, alternative day therapy; administration of proper calcium and vitamin D supplementation; or the use of other medications (i.e., H2-receptor blockers or proton pump inhibitors). In some affected individuals, certain adverse effects may necessitate a decrease in dosage or discontinuation of therapy and substitution of another appropriate treatment. However, treatment with glucocorticoids should never be abruptly stopped unless under the direct supervision of a physician.Therapy with other immunosuppressive drugs, such as azathioprine, methotrexate, mycophenoloate mofetil, cyclophosphamide, tacrolimus, or cyclosporine, may be beneficial for some affected individuals who have an insufficient response to steroid therapy alone, dose-limiting adverse effects, or frequent relapses. For example, preliminary investigations have shown that some affected individuals may benefit from combination therapy with azathioprine and steroids, with the addition of immunosuppressant therapy often allowing the use of lower steroid doses and therefore less adverse effects from the steroid treatment. Rituximab is a monoclonal antibody directed against the CD20 protein on the surface of B cells and has shown some benefit in the treatment of dermatomyositis. In addition, reports indicate that some affected individuals have obtained benefit from methotrexate therapy for five years or more and in both muscle and skin disease. However, therapy with such immunosuppressive agents may have serious adverse effects, such as an increased susceptibility to infections and other effects. In some patients who do not improve while on glucocorticoid therapy, with or without additional immunosuppressive treatment, have been shown to benefit in the short-term from receiving monthly high-dose intravenous immunoglobulin (IVIG) for 6 months. Thus, as with steroid therapy, individuals who undergo treatment with immunosuppressive agents require ongoing monitoring to ensure appropriate response, to help minimize or manage possible side effects, and to make any necessary dosage adjustments or treatment substitutions.Antimalarial agents, such as hydroxychloroquine, may be useful in treating the skin manifestations of the disease and allow for a lower dose of glucocorticoids; however, these patients may be at an increased risk of eruption associated with treatment. Calcium-channel blockers, mainly diltiazem, have been used in treating calcinosis in patients that develop calcium deposits.In affected individuals with an associated malignancy, reports suggest that dermatomyositis often improves with removal of the underlying cancer*. Experts indicate that individuals with malignancy-associated dermatomyositis may also sometimes respond to therapy with glucocorticoids such as prednisone. (*Depending upon the specific form, stage, and grade of the malignancy and other factors, recommended cancer treatment may include surgical removal of the malignancy; administration of certain chemotherapy drugs; radiation therapy; and/or other measures. During radiation therapy, radiation via x-rays or other sources of radioactivity is passed through selected regions of the body to destroy cancer cells and shrink tumors.)In some cases, physical therapy may be recommended to help improve muscle strength and avoid the development of contractures. For individuals with calcifications, physicians may sometimes recommend surgical removal of calcium deposits. Treatment for other findings potentially associated with dermatomyositis (i.e., difficulty swallowing and/or breathing; speech problems; and/or abnormalities of the heart, lungs, and/or GI tract) is symptomatic and supportive. Affected individuals should be closely monitored by physicians so that proper preventive measures may be taken to help avoid serious complications potentially associated with this disorder.Diet and physical activity also play an important role in dermatomyositis. For example, patients with severe muscle inflammation should incorporate more protein in their diet to compensate for the loss. Patients with dysphagia may require a special diet to avoid certain foods that may exacerbate their symptoms. Additional non-pharmacological recommendations include: avoidance and/or protection from the sun; elevation of the head of the bed; not eating before bedtime; and general bed rest. | Therapies of Dermatomyositis. Treatment
The treatment of dermatomyositis is directed toward the specific symptoms that are apparent in each individual and thus can vary from one patient to another. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians or internists; physicians who specialize in the diagnosis and treatment of connective tissue disorders (rheumatologists); specialists in the functioning of the immune system (immunologists); and/or other health care professionals. In general, treatment for the muscle involvement associated with dermatomyositis requires the use of glucocorticoids. Treatment for the skin findings associated with dermatomyositis includes: sun avoidance, sunscreens, topical glucocorticoids, anti-malarial agents, methotrexate, mycophenolate mofetil, and/or intravenous immunoglobulin (IVIg).Glucocorticoids, particularly prednisone, are widely used in the treatment of dermatomyositis and are often used first-line. Such medications, which are similar to the natural hormones produced by the outer region of the adrenal glands (adrenal cortex), are often used to reduce inflammation and associated swelling and also serve to suppress immune responses (immunosuppressive therapy). Blood levels of muscle enzyme (i.e., CK) activity are repeatedly measured to help monitor the effectiveness of such therapy. Reduction of these enzymes toward or reaching normal levels is noted in most affected adults within approximately six to 12 weeks after treatment is started, with subsequent improvement in muscle strength. When normal enzyme levels have been achieved, the dose of prednisone is usually slowly reduced (tapered). Dose levels are increased if muscle enzyme levels rise. Physicians may attempt to carefully, gradually withdraw such therapy periodically to determine whether the disease remains clinically active. In many cases, however, prolonged maintenance therapy with prednisone may be necessary. Yet reports indicate that some adults may appear to achieve a complete response. In such instances, therapy may be gradually withdrawn with careful ongoing monitoring.Affected children may initially require high dose therapy with prednisone, which often results in a return of muscle enzyme levels toward normal levels within about one to two weeks. As with adults, decreased muscle inflammation and improved muscle strength typically follow. Dose levels may then be slowly reduced to the lowest possible dose sufficient to maintain normal enzyme levels and improve symptoms. Generally, according to experts, children with dermatomyositis may be able to discontinue prednisone after approximately two years, experiencing an apparent cessation of symptoms (i.e., remission).High dose glucocorticoid therapy may produce adverse side effects, particularly after prolonged use, such as a decrease in bone density, causing bones to become brittle and weakened (osteoporosis); increasing, “superimposed” muscle weakness due to effects of the medication (i.e., corticosteroid myopathy); tissue swelling (edema); peptic ulcers; elevated blood pressure; elevated blood sugar levels; weight gain with fat deposits in the abdomen, face, and/or back of the neck or other findings. Physicians may recommend certain measures to help prevent or minimize adverse effects, such as appropriate, alternative day therapy; administration of proper calcium and vitamin D supplementation; or the use of other medications (i.e., H2-receptor blockers or proton pump inhibitors). In some affected individuals, certain adverse effects may necessitate a decrease in dosage or discontinuation of therapy and substitution of another appropriate treatment. However, treatment with glucocorticoids should never be abruptly stopped unless under the direct supervision of a physician.Therapy with other immunosuppressive drugs, such as azathioprine, methotrexate, mycophenoloate mofetil, cyclophosphamide, tacrolimus, or cyclosporine, may be beneficial for some affected individuals who have an insufficient response to steroid therapy alone, dose-limiting adverse effects, or frequent relapses. For example, preliminary investigations have shown that some affected individuals may benefit from combination therapy with azathioprine and steroids, with the addition of immunosuppressant therapy often allowing the use of lower steroid doses and therefore less adverse effects from the steroid treatment. Rituximab is a monoclonal antibody directed against the CD20 protein on the surface of B cells and has shown some benefit in the treatment of dermatomyositis. In addition, reports indicate that some affected individuals have obtained benefit from methotrexate therapy for five years or more and in both muscle and skin disease. However, therapy with such immunosuppressive agents may have serious adverse effects, such as an increased susceptibility to infections and other effects. In some patients who do not improve while on glucocorticoid therapy, with or without additional immunosuppressive treatment, have been shown to benefit in the short-term from receiving monthly high-dose intravenous immunoglobulin (IVIG) for 6 months. Thus, as with steroid therapy, individuals who undergo treatment with immunosuppressive agents require ongoing monitoring to ensure appropriate response, to help minimize or manage possible side effects, and to make any necessary dosage adjustments or treatment substitutions.Antimalarial agents, such as hydroxychloroquine, may be useful in treating the skin manifestations of the disease and allow for a lower dose of glucocorticoids; however, these patients may be at an increased risk of eruption associated with treatment. Calcium-channel blockers, mainly diltiazem, have been used in treating calcinosis in patients that develop calcium deposits.In affected individuals with an associated malignancy, reports suggest that dermatomyositis often improves with removal of the underlying cancer*. Experts indicate that individuals with malignancy-associated dermatomyositis may also sometimes respond to therapy with glucocorticoids such as prednisone. (*Depending upon the specific form, stage, and grade of the malignancy and other factors, recommended cancer treatment may include surgical removal of the malignancy; administration of certain chemotherapy drugs; radiation therapy; and/or other measures. During radiation therapy, radiation via x-rays or other sources of radioactivity is passed through selected regions of the body to destroy cancer cells and shrink tumors.)In some cases, physical therapy may be recommended to help improve muscle strength and avoid the development of contractures. For individuals with calcifications, physicians may sometimes recommend surgical removal of calcium deposits. Treatment for other findings potentially associated with dermatomyositis (i.e., difficulty swallowing and/or breathing; speech problems; and/or abnormalities of the heart, lungs, and/or GI tract) is symptomatic and supportive. Affected individuals should be closely monitored by physicians so that proper preventive measures may be taken to help avoid serious complications potentially associated with this disorder.Diet and physical activity also play an important role in dermatomyositis. For example, patients with severe muscle inflammation should incorporate more protein in their diet to compensate for the loss. Patients with dysphagia may require a special diet to avoid certain foods that may exacerbate their symptoms. Additional non-pharmacological recommendations include: avoidance and/or protection from the sun; elevation of the head of the bed; not eating before bedtime; and general bed rest. | 368 | Dermatomyositis |
nord_369_0 | Overview of Desmoid Tumor | SummaryDesmoid tumor commonly develops in the fibrous (connective) tissues of the body that connect, support and surround other body parts and organs. Desmoid tumors grow from a fibroblast cell known as myofibroblast, which make up connective tissue and are also important for wound healing. They can develop anywhere in the body. Superficial desmoids tend to be less aggressive than deep desmoids (abdominal, extra abdominal, mesenteric). Desmoid tumors look like dense scar tissue. They adhere to surrounding structures and organs and are often difficult to remove. Surgery has been the traditional therapy for desmoid tumors but up to 20-30% will recur after surgery.IntroductionDesmoid tumor is called aggressive fibromatosis as it has similarities with a malignant (cancerous) tumor called fibrosarcoma. Desmoid tumors do not spread (metastasize) to other parts of the body. | Overview of Desmoid Tumor. SummaryDesmoid tumor commonly develops in the fibrous (connective) tissues of the body that connect, support and surround other body parts and organs. Desmoid tumors grow from a fibroblast cell known as myofibroblast, which make up connective tissue and are also important for wound healing. They can develop anywhere in the body. Superficial desmoids tend to be less aggressive than deep desmoids (abdominal, extra abdominal, mesenteric). Desmoid tumors look like dense scar tissue. They adhere to surrounding structures and organs and are often difficult to remove. Surgery has been the traditional therapy for desmoid tumors but up to 20-30% will recur after surgery.IntroductionDesmoid tumor is called aggressive fibromatosis as it has similarities with a malignant (cancerous) tumor called fibrosarcoma. Desmoid tumors do not spread (metastasize) to other parts of the body. | 369 | Desmoid Tumor |
nord_369_1 | Symptoms of Desmoid Tumor | While each child or adult may experience symptoms differently, the following are the most common symptoms of desmoid tumors. The symptoms vary greatly depending on size and location:• A painless swelling or lump
• Pain or soreness caused by compressed nerves or muscles
• Pain and obstruction of the bowels
• Limping or other difficulty using the legs, feet, arms or hands or other affected part of the body | Symptoms of Desmoid Tumor. While each child or adult may experience symptoms differently, the following are the most common symptoms of desmoid tumors. The symptoms vary greatly depending on size and location:• A painless swelling or lump
• Pain or soreness caused by compressed nerves or muscles
• Pain and obstruction of the bowels
• Limping or other difficulty using the legs, feet, arms or hands or other affected part of the body | 369 | Desmoid Tumor |
nord_369_2 | Causes of Desmoid Tumor | The cause of the desmoid tumor is not known. Desmoid tumors may occur sporadically or may be part of a disease called familial adenomatous polyposis (FAP). FAP is a familial cancer predisposition syndrome. People affected with FAP often develop intra-abdominal desmoid tumors as well as abnormal growths called polyps and cancerous tumors in the part of the intestine called the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic. Reports in the medical literature state that 3.5-32% of people with FAP develop desmoid tumors sometime in their life. These desmoid tumors are the result of changes (pathogenic variants or mutations) in the adenomatous polyposis coli (APC) gene. However, in most people, the desmoid tumor occurs sporadically, which means that it is not caused by a predisposing genetic disease. Variants in the CTNNB1 gene or the APC gene may cause sporadic desmoid tumors. APC gene variants cause desmoid tumors associated with FAP, as well as 10% to 15% of sporadic desmoid tumors. Variants in the CTNNB1 gene have been seen in up to 85% of sporadic desmoid tumors. Both genes, APC and CTNNB1, are involved in an important cell signaling pathway that controls the cell growth and cell division as well as the process by which cells mature to carry out specific functions (differentiation). People who develop sporadic desmoid tumors do not have the other health problems seen in people with FAP who have variants in the APC gene.Other factors that may increase the risk of developing desmoid tumor are irritation or repeated trauma to a certain area of the body (including surgical trauma) and the female hormone called estrogen.Inheritance Most desmoid tumors are sporadic and are not inherited. Sporadic tumors result from genetic mutations that occur during a person's lifetime, called somatic mutations. Somatic mutations in the CTNNB1 or APC gene can cause sporadic desmoid tumors. These mutations are not inherited. FAP is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females. | Causes of Desmoid Tumor. The cause of the desmoid tumor is not known. Desmoid tumors may occur sporadically or may be part of a disease called familial adenomatous polyposis (FAP). FAP is a familial cancer predisposition syndrome. People affected with FAP often develop intra-abdominal desmoid tumors as well as abnormal growths called polyps and cancerous tumors in the part of the intestine called the colon. Desmoid tumors that are not part of an inherited condition are described as sporadic. Reports in the medical literature state that 3.5-32% of people with FAP develop desmoid tumors sometime in their life. These desmoid tumors are the result of changes (pathogenic variants or mutations) in the adenomatous polyposis coli (APC) gene. However, in most people, the desmoid tumor occurs sporadically, which means that it is not caused by a predisposing genetic disease. Variants in the CTNNB1 gene or the APC gene may cause sporadic desmoid tumors. APC gene variants cause desmoid tumors associated with FAP, as well as 10% to 15% of sporadic desmoid tumors. Variants in the CTNNB1 gene have been seen in up to 85% of sporadic desmoid tumors. Both genes, APC and CTNNB1, are involved in an important cell signaling pathway that controls the cell growth and cell division as well as the process by which cells mature to carry out specific functions (differentiation). People who develop sporadic desmoid tumors do not have the other health problems seen in people with FAP who have variants in the APC gene.Other factors that may increase the risk of developing desmoid tumor are irritation or repeated trauma to a certain area of the body (including surgical trauma) and the female hormone called estrogen.Inheritance Most desmoid tumors are sporadic and are not inherited. Sporadic tumors result from genetic mutations that occur during a person's lifetime, called somatic mutations. Somatic mutations in the CTNNB1 or APC gene can cause sporadic desmoid tumors. These mutations are not inherited. FAP is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females. | 369 | Desmoid Tumor |
nord_369_3 | Affects of Desmoid Tumor | Desmoid tumors constitute 0.03% of all tumors. The estimated incidence in the general population is 2-4 per million people per year. Desmoid tumors are observed to be more common in persons aged 10-40 years but can occur in other age groups. Desmoid tumors can commonly occur in women after childbirth. The female: male gender ratio is 2:1. In children, the incidence is the same in males and females. | Affects of Desmoid Tumor. Desmoid tumors constitute 0.03% of all tumors. The estimated incidence in the general population is 2-4 per million people per year. Desmoid tumors are observed to be more common in persons aged 10-40 years but can occur in other age groups. Desmoid tumors can commonly occur in women after childbirth. The female: male gender ratio is 2:1. In children, the incidence is the same in males and females. | 369 | Desmoid Tumor |
nord_369_4 | Related disorders of Desmoid Tumor | Gardner’s syndrome is a genetic disorder characterized by multiple colonic polyps and tumors outside the colon. The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The multiple colon polyps predispose to development of colon cancer. Gardner’s syndrome is caused by variants in the APC gene and is recognized as a type of FAP. If one parent has Gardner’s syndrome, each of their male or female children are at 50% risk of inheriting the APC gene and developing Gardner’s syndrome.Dermatofibrosarcoma is a cutaneous malignancy that arises from the dermis and invades deeper subcutaneous tissue such as fat tissue, fascia, muscle and bone. Its cause is unknown. Chromosomal abnormalities may contribute to the cause of dermatofibrosarcoma, especially a chromosomal translocation between chromosomes 17 and 22 that fuses the collagen gene (COL1A1) with the platelet-deprived growth factor gene. However, no evidence of hereditary or familial predisposition exists. In 10-20% of affected patients, trauma at the site may be involved. Surgical, old burn, and sites of vaccination scarring have all been reported as sites of dermatofibrosarcoma. Dermatofibrosarcoma is a slow growing tumor. Because of slow progression and initial growth as a small asymptomatic papule, the diagnosis is often delayed. The tumor may gradually enlarge into a lumpy nodule or evolve into an atrophic and/or sclerotic plaque.Fibrosarcomas are malignant tumors derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells. They originate in the connective fibrous tissue at the ends of arm or leg bones and then spread to other surrounding tissues such as fat, muscles tendons, nerves, joint tissue or blood vessels. There are two forms of fibrosarcoma. Infantile or congenital fibrosarcoma is the most common soft tissue sarcoma found in children less than one year of age. It presents as a rapidly growing mass at birth or shortly after. This fibrosarcoma is usually slow-growing and tends to be more benign than fibrosarcoma in older children, which behaves more like the type found in adults. The adult form of fibrosarcoma can occur in older children and in adolescents especially between the ages of 10 to 15. | Related disorders of Desmoid Tumor. Gardner’s syndrome is a genetic disorder characterized by multiple colonic polyps and tumors outside the colon. The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The multiple colon polyps predispose to development of colon cancer. Gardner’s syndrome is caused by variants in the APC gene and is recognized as a type of FAP. If one parent has Gardner’s syndrome, each of their male or female children are at 50% risk of inheriting the APC gene and developing Gardner’s syndrome.Dermatofibrosarcoma is a cutaneous malignancy that arises from the dermis and invades deeper subcutaneous tissue such as fat tissue, fascia, muscle and bone. Its cause is unknown. Chromosomal abnormalities may contribute to the cause of dermatofibrosarcoma, especially a chromosomal translocation between chromosomes 17 and 22 that fuses the collagen gene (COL1A1) with the platelet-deprived growth factor gene. However, no evidence of hereditary or familial predisposition exists. In 10-20% of affected patients, trauma at the site may be involved. Surgical, old burn, and sites of vaccination scarring have all been reported as sites of dermatofibrosarcoma. Dermatofibrosarcoma is a slow growing tumor. Because of slow progression and initial growth as a small asymptomatic papule, the diagnosis is often delayed. The tumor may gradually enlarge into a lumpy nodule or evolve into an atrophic and/or sclerotic plaque.Fibrosarcomas are malignant tumors derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells. They originate in the connective fibrous tissue at the ends of arm or leg bones and then spread to other surrounding tissues such as fat, muscles tendons, nerves, joint tissue or blood vessels. There are two forms of fibrosarcoma. Infantile or congenital fibrosarcoma is the most common soft tissue sarcoma found in children less than one year of age. It presents as a rapidly growing mass at birth or shortly after. This fibrosarcoma is usually slow-growing and tends to be more benign than fibrosarcoma in older children, which behaves more like the type found in adults. The adult form of fibrosarcoma can occur in older children and in adolescents especially between the ages of 10 to 15. | 369 | Desmoid Tumor |
nord_369_5 | Diagnosis of Desmoid Tumor | The conclusive diagnosis of desmoid tumor requires a biopsy. Microscopic examination of the biopsy tissue confirms the diagnosis. On microscopic examination, the spindle cells of desmoid tumors appear to be myofibroblasts and are thought to be an abnormal proliferation of myofibroblasts, which normally gradually disappear during the later stages of wound healing. Additionally, immunohistochemical stains can establish the nuclear accumulation of beta-catenin, a protein that is caused by the genetic mutations usually found in desmoid tumors. Nuclear reactivity shows relatively high specificity, detected in up to 90% of desmoids, regardless of site. Finally, antibodies are often examined in desmoid tumors, including smooth muscle actin, desmin and KIT, to aid in distinguishing them from other tumors. | Diagnosis of Desmoid Tumor. The conclusive diagnosis of desmoid tumor requires a biopsy. Microscopic examination of the biopsy tissue confirms the diagnosis. On microscopic examination, the spindle cells of desmoid tumors appear to be myofibroblasts and are thought to be an abnormal proliferation of myofibroblasts, which normally gradually disappear during the later stages of wound healing. Additionally, immunohistochemical stains can establish the nuclear accumulation of beta-catenin, a protein that is caused by the genetic mutations usually found in desmoid tumors. Nuclear reactivity shows relatively high specificity, detected in up to 90% of desmoids, regardless of site. Finally, antibodies are often examined in desmoid tumors, including smooth muscle actin, desmin and KIT, to aid in distinguishing them from other tumors. | 369 | Desmoid Tumor |
nord_369_6 | Therapies of Desmoid Tumor | Treatment
Depending on the extent of the tumor growth and the overall condition of the patient, the following treatment options are utilized. Over the past several years first-line treatment has transitioned from surgery to a period of watchful waiting as initial therapy.Watchful waiting is a manner of treating the tumor with close surveillance utilizing imaging and exams. Desmoid tumors do not metastasize and have been shown to spontaneously regress in up to 20% of patients. Treatment with surgery, chemotherapy and/or radiation can cause significant illness and even death, so patients with asymptomatic or minimally symptomatic disease that has stable appearance on screening modalities are treated with watchful waiting.For those with significant symptoms or concern that growth would lead to impact on nearby structures, treatment with surgery and medical therapies is the next step in treatment. Surgery alone is often the only treatment needed. However, the recurrence rate of desmoid tumor is often as high as 30% and more than one surgery may be needed. The tumor tends to become more aggressive when it recurs after resection.Sorafenib is an oral chemotherapy known as a molecular-targeted therapy. In a clinical trial 33% of patients had shrinkage of their tumor with sorafenib and up to 70% of tumors did not grow. This led to sorafenib being a first line treatment for many, particularly patients for whom surgery is not an option.Pazopanib is another multi-kinase inhibitor that has shown similar results. Intravenous chemotherapy including anthracylcline agents (i.e., doxorubicin), methotrexate/vinblasticne are another class of medications used to treat tumors when they are not surgically removable due to size or location. These have more toxicities than the targeted therapies and are often a second choice.Anti-inflammatory drugs may make the tumor slowly shrink. Non-steroidal anti-inflammatory drugs (NSAIDs) alone and in conjunction with other therapies mentioned here have been used to treat desmoid tumors. Some hormones seem to increase the growth of desmoid tumors, so anti-hormonal medications such as anti-estrogens and prostaglandin inhibitors have also been used. Since the advent of targeted therapies with better response rates the use of NSAIDS and hormone therapy is limited.High-energy rays (radiation) from a specialized machine can be used to damage or kill cancer cells and shrink tumors. For desmoids it is used as treatment for recurrent disease that doesn’t respond to other treatments or as primary therapy to avoid surgical or medical therapy toxicities.After surgery, MRI is used to monitor recurrence in the arms and legs. CAT scans are used to monitor intra-abdominal and chest desmoids. | Therapies of Desmoid Tumor. Treatment
Depending on the extent of the tumor growth and the overall condition of the patient, the following treatment options are utilized. Over the past several years first-line treatment has transitioned from surgery to a period of watchful waiting as initial therapy.Watchful waiting is a manner of treating the tumor with close surveillance utilizing imaging and exams. Desmoid tumors do not metastasize and have been shown to spontaneously regress in up to 20% of patients. Treatment with surgery, chemotherapy and/or radiation can cause significant illness and even death, so patients with asymptomatic or minimally symptomatic disease that has stable appearance on screening modalities are treated with watchful waiting.For those with significant symptoms or concern that growth would lead to impact on nearby structures, treatment with surgery and medical therapies is the next step in treatment. Surgery alone is often the only treatment needed. However, the recurrence rate of desmoid tumor is often as high as 30% and more than one surgery may be needed. The tumor tends to become more aggressive when it recurs after resection.Sorafenib is an oral chemotherapy known as a molecular-targeted therapy. In a clinical trial 33% of patients had shrinkage of their tumor with sorafenib and up to 70% of tumors did not grow. This led to sorafenib being a first line treatment for many, particularly patients for whom surgery is not an option.Pazopanib is another multi-kinase inhibitor that has shown similar results. Intravenous chemotherapy including anthracylcline agents (i.e., doxorubicin), methotrexate/vinblasticne are another class of medications used to treat tumors when they are not surgically removable due to size or location. These have more toxicities than the targeted therapies and are often a second choice.Anti-inflammatory drugs may make the tumor slowly shrink. Non-steroidal anti-inflammatory drugs (NSAIDs) alone and in conjunction with other therapies mentioned here have been used to treat desmoid tumors. Some hormones seem to increase the growth of desmoid tumors, so anti-hormonal medications such as anti-estrogens and prostaglandin inhibitors have also been used. Since the advent of targeted therapies with better response rates the use of NSAIDS and hormone therapy is limited.High-energy rays (radiation) from a specialized machine can be used to damage or kill cancer cells and shrink tumors. For desmoids it is used as treatment for recurrent disease that doesn’t respond to other treatments or as primary therapy to avoid surgical or medical therapy toxicities.After surgery, MRI is used to monitor recurrence in the arms and legs. CAT scans are used to monitor intra-abdominal and chest desmoids. | 369 | Desmoid Tumor |
nord_370_0 | Overview of Dextrocardia with Situs Inversus | Dextrocardia with Situs Inversus is a rare heart condition characterized by abnormal positioning of the heart. In this condition, the tip of the heart (apex) is positioned on the right side of the chest. Additionally, the position of the heart chambers as well as the visceral organs such as the liver and spleen is reversed (situs inversus). However, most affected individuals can live a normal life without associated symptoms or disability. | Overview of Dextrocardia with Situs Inversus. Dextrocardia with Situs Inversus is a rare heart condition characterized by abnormal positioning of the heart. In this condition, the tip of the heart (apex) is positioned on the right side of the chest. Additionally, the position of the heart chambers as well as the visceral organs such as the liver and spleen is reversed (situs inversus). However, most affected individuals can live a normal life without associated symptoms or disability. | 370 | Dextrocardia with Situs Inversus |
nord_370_1 | Symptoms of Dextrocardia with Situs Inversus | Electrocardiography reveals an inversion of the electrical waves from the heart and is the diagnostic measure of choice. | Symptoms of Dextrocardia with Situs Inversus. Electrocardiography reveals an inversion of the electrical waves from the heart and is the diagnostic measure of choice. | 370 | Dextrocardia with Situs Inversus |
nord_370_2 | Causes of Dextrocardia with Situs Inversus | Dextrocardia with Situs Inversus, a rare condition that is present at birth, is transmitted by autosomal recessive genes. The primitive loop in the embryo moves into the reverse direction of its normal position during fetal development, causing displacement of organs. Human traits including the classic genetic disorders are the product of the interaction of two genes for that condition, one received from the father and one from the mother. 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 Dextrocardia with Situs Inversus. Dextrocardia with Situs Inversus, a rare condition that is present at birth, is transmitted by autosomal recessive genes. The primitive loop in the embryo moves into the reverse direction of its normal position during fetal development, causing displacement of organs. Human traits including the classic genetic disorders are the product of the interaction of two genes for that condition, one received from the father and one from the mother. 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. | 370 | Dextrocardia with Situs Inversus |
nord_370_3 | Affects of Dextrocardia with Situs Inversus | Dextrocardia with Situs Inversus is present at birth. The condition affects males and females in equal numbers. | Affects of Dextrocardia with Situs Inversus. Dextrocardia with Situs Inversus is present at birth. The condition affects males and females in equal numbers. | 370 | Dextrocardia with Situs Inversus |
nord_370_4 | Related disorders of Dextrocardia with Situs Inversus | Dextroversion of the heart means that the location of the heart is abnormally positioned in the right half of the chest. The left ventricle remains on the left, but lies in front of the right ventricle. The heart is rotated to the right. The waves representing the heart beat on the electrocardiogram will indicate an abnormality.Dextroposition of the heart is a displacement of the heart to the right. It is usually caused by acquired disease of the lungs, the membrane around the lungs (pleura), or diaphragm. The electrocardiogram is usually normal.Kartagener Syndrome is a combination of Dextrocardia with chronic dilatation of the bronchi, difficulty breathing, recurrent respiratory infection (bronchiectasis) and infection of the sinuses (sinusitis). Clubbed fingers and bluish discoloration of the skin (cyanosis) may also be present. | Related disorders of Dextrocardia with Situs Inversus. Dextroversion of the heart means that the location of the heart is abnormally positioned in the right half of the chest. The left ventricle remains on the left, but lies in front of the right ventricle. The heart is rotated to the right. The waves representing the heart beat on the electrocardiogram will indicate an abnormality.Dextroposition of the heart is a displacement of the heart to the right. It is usually caused by acquired disease of the lungs, the membrane around the lungs (pleura), or diaphragm. The electrocardiogram is usually normal.Kartagener Syndrome is a combination of Dextrocardia with chronic dilatation of the bronchi, difficulty breathing, recurrent respiratory infection (bronchiectasis) and infection of the sinuses (sinusitis). Clubbed fingers and bluish discoloration of the skin (cyanosis) may also be present. | 370 | Dextrocardia with Situs Inversus |
nord_370_5 | Diagnosis of Dextrocardia with Situs Inversus | Diagnosis of Dextrocardia with Situs Inversus. | 370 | Dextrocardia with Situs Inversus |
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nord_370_6 | Therapies of Dextrocardia with Situs Inversus | Treatment of Dextrocardia with Situs Inversus is symptomatic and supportive when needed. In most cases, affected individuals can live a normal life without any symptoms or discomfort. If the condition is associated with other more serious heart malformations, the prognosis and treatment will vary. Genetic counseling may be helpful for affected families. | Therapies of Dextrocardia with Situs Inversus. Treatment of Dextrocardia with Situs Inversus is symptomatic and supportive when needed. In most cases, affected individuals can live a normal life without any symptoms or discomfort. If the condition is associated with other more serious heart malformations, the prognosis and treatment will vary. Genetic counseling may be helpful for affected families. | 370 | Dextrocardia with Situs Inversus |
nord_371_0 | Overview of Diamond Blackfan Anemia | Diamond Blackfan anemia (DBA) is a rare blood disorder that affects the bone marrow. The function of the bone marrow is to make new blood cells, including red blood cells (which carry oxygen to the body’s tissues), white blood cells (which help the body fight infections), and platelets (which help the body stop bleeding). In DBA the bone marrow cannot make enough red blood cells to meet the body’s needs. DBA is characterized by a shortage of red blood cells which usually becomes evident during the first year of life when the patient develops anemia. About half of the affected patients have abnormal physical abnormalities associated with DBA. The symptoms and physical findings associated with DBA vary greatly from person to person. | Overview of Diamond Blackfan Anemia. Diamond Blackfan anemia (DBA) is a rare blood disorder that affects the bone marrow. The function of the bone marrow is to make new blood cells, including red blood cells (which carry oxygen to the body’s tissues), white blood cells (which help the body fight infections), and platelets (which help the body stop bleeding). In DBA the bone marrow cannot make enough red blood cells to meet the body’s needs. DBA is characterized by a shortage of red blood cells which usually becomes evident during the first year of life when the patient develops anemia. About half of the affected patients have abnormal physical abnormalities associated with DBA. The symptoms and physical findings associated with DBA vary greatly from person to person. | 371 | Diamond Blackfan Anemia |
nord_371_1 | Symptoms of Diamond Blackfan Anemia | Diamond Blackfan anemia is characterized by moderate to severe deficiency of red blood cells (anemia). Sometimes white blood cells and platelets may be lower as well. Symptoms of anemia include rapid heartbeat, pale skin, sleepiness, irritability, poor appetite, and weakness. Approximately ninety percent of affected patients are diagnosed within the first year of life. The diagnosis is generally made by 3-4 months of age.Approximately one-half of those affected have physical abnormalities, such as small head size; wide-set eyes; flat nose; small, low-set ears; small bottom jaw; recessed or small chin; cleft palate (an opening in the roof of the mouth with or without a cleft lip – a split in the upper lip); and small, missing or extra thumb(s). The neck may be short due to fused vertebrae and shoulder blades may be prominent. About one-third of affected individuals have slow growth leading to short stature.Other features of DBA may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), kidney abnormalities; defects of the heart; and males may have hypospadias (a condition in which the urinary tract does not end at the tip of the penis). Many of these defects may need surgical correction.A possible complication of DBA is the development of cancer at younger than expected ages. Patients with DBA have developed bone cancer (osteosarcoma), colon cancer, and leukemia (blood cancer called acute myeloid leukemia), among others. The patients are also at risk for a pre-leukemic syndrome called myelodysplastic syndrome which is another disorder caused by the bone marrow not making enough healthy blood cells. | Symptoms of Diamond Blackfan Anemia. Diamond Blackfan anemia is characterized by moderate to severe deficiency of red blood cells (anemia). Sometimes white blood cells and platelets may be lower as well. Symptoms of anemia include rapid heartbeat, pale skin, sleepiness, irritability, poor appetite, and weakness. Approximately ninety percent of affected patients are diagnosed within the first year of life. The diagnosis is generally made by 3-4 months of age.Approximately one-half of those affected have physical abnormalities, such as small head size; wide-set eyes; flat nose; small, low-set ears; small bottom jaw; recessed or small chin; cleft palate (an opening in the roof of the mouth with or without a cleft lip – a split in the upper lip); and small, missing or extra thumb(s). The neck may be short due to fused vertebrae and shoulder blades may be prominent. About one-third of affected individuals have slow growth leading to short stature.Other features of DBA may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), kidney abnormalities; defects of the heart; and males may have hypospadias (a condition in which the urinary tract does not end at the tip of the penis). Many of these defects may need surgical correction.A possible complication of DBA is the development of cancer at younger than expected ages. Patients with DBA have developed bone cancer (osteosarcoma), colon cancer, and leukemia (blood cancer called acute myeloid leukemia), among others. The patients are also at risk for a pre-leukemic syndrome called myelodysplastic syndrome which is another disorder caused by the bone marrow not making enough healthy blood cells. | 371 | Diamond Blackfan Anemia |
nord_371_2 | Causes of Diamond Blackfan Anemia | Diamond Blackfan anemia is caused by changes (mutations) in ribosomal protein genes in about 80-85% of those affected. In the remaining 10-15% of patients, no abnormal genes have yet been identified.A mutation in the RPS19 gene is the cause of DBA in about 25% of patients. Mutations have also been found in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26, and rarely in RPL15, RPL17, RPL19, RPL26, RPL27, RPL31, RPS15A, RPS20, RPS27, RPS28, RPS29, and TSR2. In a few patients, the disease is caused by a mutation in the GATA1 gene.DBA caused by the ribosomal protein gene mutation follows autosomal dominant inheritance. 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 (changed) gene in the affected individual only. In approximately 45% of patients, the mutation is inherited from one affected parent. The remaining patients have no history of the disorder in their family, and develop the disorder because of a new (sporadic) gene mutation. 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. The rare TSR2 and GATA1 gene mutations are inherited in affected males only from a mother who is an unaffected carrier. | Causes of Diamond Blackfan Anemia. Diamond Blackfan anemia is caused by changes (mutations) in ribosomal protein genes in about 80-85% of those affected. In the remaining 10-15% of patients, no abnormal genes have yet been identified.A mutation in the RPS19 gene is the cause of DBA in about 25% of patients. Mutations have also been found in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26, and rarely in RPL15, RPL17, RPL19, RPL26, RPL27, RPL31, RPS15A, RPS20, RPS27, RPS28, RPS29, and TSR2. In a few patients, the disease is caused by a mutation in the GATA1 gene.DBA caused by the ribosomal protein gene mutation follows autosomal dominant inheritance. 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 (changed) gene in the affected individual only. In approximately 45% of patients, the mutation is inherited from one affected parent. The remaining patients have no history of the disorder in their family, and develop the disorder because of a new (sporadic) gene mutation. 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. The rare TSR2 and GATA1 gene mutations are inherited in affected males only from a mother who is an unaffected carrier. | 371 | Diamond Blackfan Anemia |
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