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Diagnosis of MELAS Syndrome
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MELAS is diagnosed based on clinical findings and molecular genetic testing.Clinical testing may include measurement of lactate and pyruvate concentrations and CSF protein which are elevated in MELAS syndrome. Brain imaging techniques such as magnetic resonance imaging (MRI) may be used to look for stroke-like lesions and magnetic resonance spectroscopy (MRS) may be used to look for a lactate peak in the brain. Electrocardiogram may be used to diagnose heart rhythm abnormalities and echocardiogram may be used to diagnose cardiomyopathy. Muscle biopsy will usually show ragged red fibers.The mtDNA mutations associated with MELAS can usually be detected in white blood cells, but due to heteroplasmy (see Causes), other tissue samples may be necessary such as skin, hair follicles, urinary sediment and skeletal muscle. Urinary sediment has the best yield for detecting the mutation when compared to blood, skin, and hair follicles.
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Diagnosis of MELAS Syndrome. MELAS is diagnosed based on clinical findings and molecular genetic testing.Clinical testing may include measurement of lactate and pyruvate concentrations and CSF protein which are elevated in MELAS syndrome. Brain imaging techniques such as magnetic resonance imaging (MRI) may be used to look for stroke-like lesions and magnetic resonance spectroscopy (MRS) may be used to look for a lactate peak in the brain. Electrocardiogram may be used to diagnose heart rhythm abnormalities and echocardiogram may be used to diagnose cardiomyopathy. Muscle biopsy will usually show ragged red fibers.The mtDNA mutations associated with MELAS can usually be detected in white blood cells, but due to heteroplasmy (see Causes), other tissue samples may be necessary such as skin, hair follicles, urinary sediment and skeletal muscle. Urinary sediment has the best yield for detecting the mutation when compared to blood, skin, and hair follicles.
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MELAS Syndrome
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nord_785_6
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Therapies of MELAS Syndrome
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TreatmentNo specific treatment is available for MELAS syndrome. Anti-convulsant drugs are used to help prevent and control seizures associated with MELAS syndrome. Valproic acid should not be used as an anticonvulsant. Cochlear implants have been used to treat sensorineural deafness. Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme q10 and L-carnitine have been beneficial in some patients. In patients with mitochondrial myopathies in general, moderate treadmill training may result in improvement of aerobic capacity and drop in resting lactate levels. The use of intravenous L-arginine has been reported to improve the symptoms of disease during the acute stroke-like episodes. The use of oral arginine has been reported to decrease the recurrence of stroke-like episodes when used during the asymptomatic period.Genetic counseling is recommended for affected individuals and their families.
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Therapies of MELAS Syndrome. TreatmentNo specific treatment is available for MELAS syndrome. Anti-convulsant drugs are used to help prevent and control seizures associated with MELAS syndrome. Valproic acid should not be used as an anticonvulsant. Cochlear implants have been used to treat sensorineural deafness. Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme q10 and L-carnitine have been beneficial in some patients. In patients with mitochondrial myopathies in general, moderate treadmill training may result in improvement of aerobic capacity and drop in resting lactate levels. The use of intravenous L-arginine has been reported to improve the symptoms of disease during the acute stroke-like episodes. The use of oral arginine has been reported to decrease the recurrence of stroke-like episodes when used during the asymptomatic period.Genetic counseling is recommended for affected individuals and their families.
| 785 |
MELAS Syndrome
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nord_786_0
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Overview of Meleda Disease
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Meleda disease is an extremely rare inherited skin disorder characterized by the slowly progressive development of dry, thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red (erythema) and become abnormally thick and scaly (symmetrical cornification). Affected children may also exhibit various abnormalities of the nails; excessive sweating (hyperhidrosis) associated with an unpleasant odor; and/or, in some cases, development of small, firm raised lesions (lichenoid plaques). The range and severity of symptoms may vary from case to case. Meleda disease is inherited as an autosomal recessive trait.
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Overview of Meleda Disease. Meleda disease is an extremely rare inherited skin disorder characterized by the slowly progressive development of dry, thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red (erythema) and become abnormally thick and scaly (symmetrical cornification). Affected children may also exhibit various abnormalities of the nails; excessive sweating (hyperhidrosis) associated with an unpleasant odor; and/or, in some cases, development of small, firm raised lesions (lichenoid plaques). The range and severity of symptoms may vary from case to case. Meleda disease is inherited as an autosomal recessive trait.
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Meleda Disease
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nord_786_1
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Symptoms of Meleda Disease
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Meleda disease is an extremely rare inherited skin disorder that is usually obvious shortly after birth. Initially, affected infants may have unusually red skin on the palms of the hands and the soles of the feet (palmoplantar erythema). The affected skin then becomes abnormally thick, yellowish-brown, and scale-like (hyperkeratosis). These skin lesions are usually present on both sides of the body (bilateral) on the same respective areas (symmetrical palmoplantar keratosis). As the child grows older, these patches may spread to involve the entire hand or foot. Eventually, the wrists, forearms, and knees may also become involved. In some cases, with advancing age, the skin on the chest and abdomen may also become dry, scaly, and cracked. Excessively dry skin may cause pain and discomfort. Individuals with Meleda disease may also have unusually red skin around the mouth (perioral erythema). In addition, affected children exhibit various abnormalities of the nails (nail dystrophy). The nails may become excessively hard and thick (pachyonychia); “spoon-shaped” (koilonychia); or “hooked” (onychogryphosis) in appearance. In some cases, affected individuals may also have excessive hair growth on the hands or feet.Some individuals with Meleda disease may exhibit small, firm raised skin lesions (lichenoid plaques) in areas affected by hyperkeratosis. In addition, in most cases, affected individuals may exhibit excessive sweating (hyperhidrosis) that may be associated with an unpleasant odor. Additional features associated with Meleda disease may include abnormal webbing (fusion) of the fingers and/or toes (syndactyly), abnormal shortening of the fingers and toes (brachydactyly), and/or a grooved, cracked tongue (lingua plicata).
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Symptoms of Meleda Disease. Meleda disease is an extremely rare inherited skin disorder that is usually obvious shortly after birth. Initially, affected infants may have unusually red skin on the palms of the hands and the soles of the feet (palmoplantar erythema). The affected skin then becomes abnormally thick, yellowish-brown, and scale-like (hyperkeratosis). These skin lesions are usually present on both sides of the body (bilateral) on the same respective areas (symmetrical palmoplantar keratosis). As the child grows older, these patches may spread to involve the entire hand or foot. Eventually, the wrists, forearms, and knees may also become involved. In some cases, with advancing age, the skin on the chest and abdomen may also become dry, scaly, and cracked. Excessively dry skin may cause pain and discomfort. Individuals with Meleda disease may also have unusually red skin around the mouth (perioral erythema). In addition, affected children exhibit various abnormalities of the nails (nail dystrophy). The nails may become excessively hard and thick (pachyonychia); “spoon-shaped” (koilonychia); or “hooked” (onychogryphosis) in appearance. In some cases, affected individuals may also have excessive hair growth on the hands or feet.Some individuals with Meleda disease may exhibit small, firm raised skin lesions (lichenoid plaques) in areas affected by hyperkeratosis. In addition, in most cases, affected individuals may exhibit excessive sweating (hyperhidrosis) that may be associated with an unpleasant odor. Additional features associated with Meleda disease may include abnormal webbing (fusion) of the fingers and/or toes (syndactyly), abnormal shortening of the fingers and toes (brachydactyly), and/or a grooved, cracked tongue (lingua plicata).
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Meleda Disease
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nord_786_2
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Causes of Meleda Disease
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Meleda disease is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. 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%. Some individuals with Meleda disease have had parents who were related by blood (consanguineous). All individuals carry a few 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. Investigators have determined that some cases of Meleda disease may be caused by disruption or changes (mutations) of the ARS gene located on the long arm (q) of chromosome 8 (8q24.3). The ARS gene encodes a protein known as SLURP-1, which researchers believe is involved in cell signaling and adhesion. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. 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 8q24.3” refers to band 24.3 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
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Causes of Meleda Disease. Meleda disease is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. 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%. Some individuals with Meleda disease have had parents who were related by blood (consanguineous). All individuals carry a few 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. Investigators have determined that some cases of Meleda disease may be caused by disruption or changes (mutations) of the ARS gene located on the long arm (q) of chromosome 8 (8q24.3). The ARS gene encodes a protein known as SLURP-1, which researchers believe is involved in cell signaling and adhesion. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes, which include one X and one Y chromosome in males and two X chromosomes in females. 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 8q24.3” refers to band 24.3 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
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Meleda Disease
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nord_786_3
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Affects of Meleda Disease
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Meleda disease is an extremely rare disorder that affects males and females in equal numbers. More than 100 cases have been reported in the medical literature. The prevalence of Meleda disease in the general population is estimated at one case per 100,000 people. Skin abnormalities associated with this disorder may be present at birth (congenital). Other symptoms usually become apparent by the second or third year of life.According to the medical literature, Meleda disease was first identified in 1898 among people on the Island of Meleda in Dalmatia, Yugoslavia. Most of the original cases reported of this disorder were from that region. However, in the past 25 years many cases have been reported in various countries.
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Affects of Meleda Disease. Meleda disease is an extremely rare disorder that affects males and females in equal numbers. More than 100 cases have been reported in the medical literature. The prevalence of Meleda disease in the general population is estimated at one case per 100,000 people. Skin abnormalities associated with this disorder may be present at birth (congenital). Other symptoms usually become apparent by the second or third year of life.According to the medical literature, Meleda disease was first identified in 1898 among people on the Island of Meleda in Dalmatia, Yugoslavia. Most of the original cases reported of this disorder were from that region. However, in the past 25 years many cases have been reported in various countries.
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Meleda Disease
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nord_786_4
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Related disorders of Meleda Disease
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Symptoms of the following disorders can be similar to those of Meleda disease. Comparisons may be useful for a differential diagnosis: Papillon-Lefevre syndrome is an extremely rare inherited disorder characterized by the development of dry scaly patches of skin on the palms of the hands and the soles of the feet (palmar-plantar hyperkeratosis) as well as severe inflammation and degeneration of the structures that surround and support the teeth (periodontium), resulting in premature tooth loss (periodontoclasia). Affected individuals may also have frequent pus-producing (pyogenic) skin infections and abnormalities of the nails (nail dystrophy). They may also perspire heavily and frequently (hyperhidrosis). Papillon-Lefevre syndrome is believed to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Papillon Lefevre” as your search term in the Rare Disease Database.) Cochin Jewish disorder is a rare inherited disorder characterized by the development of red, scaly thickened patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis), frequent pus-producing (pyogenic) skin infections, overgrowth (hypertrophy) of the fingernails and toenails (onychogryphosis), and degeneration of the structures that surround and support the teeth (periodontosis). Periodontosis usually results in the premature loss of teeth. Affected individuals may also have flat feet (pes planus) and abnormally long, slender fingers and toes (arachnodactyly). Most individuals with this disorder experience numbness and tingling and lack normal blood flow to the fingers and/or toes when exposed to cold temperatures. They also often exhibit loss of bone tissue at the ends of the fingers and/or toes (acroosteolysis). Cochin Jewish disorder is thought to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Cochin Jewish” as your search term in the Rare Disease Database.) Mal de Naxos is an extremely rare inherited disorder characterized by the slow progressive development of dry scaly skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red and become abnormally thick (congenital symmetrical cornification). Affected individuals may also have hair that is curly, rough, and dense. In addition, affected children may exhibit heart (cardiac) defects, such as an abnormally large heart (cardiomegaly). Mal de Naxos is thought to be inherited as an autosomal recessive genetic trait.Jadassohn-Lewandowsky type pachyonychia congenita is a rare inherited disorder characterized by reddening, dryness, and a scaly appearance of the skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis) and/or overgrowth and malformation of the fingernails and toenails (onychogryphosis). In addition, affected infants may have teeth that are present at birth (neonatal dentition). Additional features may include loss of scalp hair, excessive sweating (hyperhidrosis) of the hands and feet, hoarseness, and/or, in some cases, respiratory distress. Mental retardation may be present in some cases. Jadassohn-Lewandowsky type pachyonychia congenita is thought to be inherited as an autosomal dominant genetic trait. Keratosis palmaris et plantaris of unna-thost (Greither's disease) is a very rare inherited skin disorder characterized by unusual whitish or yellowish thick patches of skin (keratosis) on the palms of the hands and/or the soles of the feet. Skin lesions stop at the lateral surfaces of the palms of the hands and/or the soles of the feet. In most cases, affected individuals also exhibit excessive sweating (hyperhidrosis) and unusually-shaped, thick nails. Most cases of this disorder are inherited as an autosomal dominant genetic trait; however, a severe autosomal recessive form has not been ruled out.
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Related disorders of Meleda Disease. Symptoms of the following disorders can be similar to those of Meleda disease. Comparisons may be useful for a differential diagnosis: Papillon-Lefevre syndrome is an extremely rare inherited disorder characterized by the development of dry scaly patches of skin on the palms of the hands and the soles of the feet (palmar-plantar hyperkeratosis) as well as severe inflammation and degeneration of the structures that surround and support the teeth (periodontium), resulting in premature tooth loss (periodontoclasia). Affected individuals may also have frequent pus-producing (pyogenic) skin infections and abnormalities of the nails (nail dystrophy). They may also perspire heavily and frequently (hyperhidrosis). Papillon-Lefevre syndrome is believed to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Papillon Lefevre” as your search term in the Rare Disease Database.) Cochin Jewish disorder is a rare inherited disorder characterized by the development of red, scaly thickened patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis), frequent pus-producing (pyogenic) skin infections, overgrowth (hypertrophy) of the fingernails and toenails (onychogryphosis), and degeneration of the structures that surround and support the teeth (periodontosis). Periodontosis usually results in the premature loss of teeth. Affected individuals may also have flat feet (pes planus) and abnormally long, slender fingers and toes (arachnodactyly). Most individuals with this disorder experience numbness and tingling and lack normal blood flow to the fingers and/or toes when exposed to cold temperatures. They also often exhibit loss of bone tissue at the ends of the fingers and/or toes (acroosteolysis). Cochin Jewish disorder is thought to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Cochin Jewish” as your search term in the Rare Disease Database.) Mal de Naxos is an extremely rare inherited disorder characterized by the slow progressive development of dry scaly skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red and become abnormally thick (congenital symmetrical cornification). Affected individuals may also have hair that is curly, rough, and dense. In addition, affected children may exhibit heart (cardiac) defects, such as an abnormally large heart (cardiomegaly). Mal de Naxos is thought to be inherited as an autosomal recessive genetic trait.Jadassohn-Lewandowsky type pachyonychia congenita is a rare inherited disorder characterized by reddening, dryness, and a scaly appearance of the skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis) and/or overgrowth and malformation of the fingernails and toenails (onychogryphosis). In addition, affected infants may have teeth that are present at birth (neonatal dentition). Additional features may include loss of scalp hair, excessive sweating (hyperhidrosis) of the hands and feet, hoarseness, and/or, in some cases, respiratory distress. Mental retardation may be present in some cases. Jadassohn-Lewandowsky type pachyonychia congenita is thought to be inherited as an autosomal dominant genetic trait. Keratosis palmaris et plantaris of unna-thost (Greither's disease) is a very rare inherited skin disorder characterized by unusual whitish or yellowish thick patches of skin (keratosis) on the palms of the hands and/or the soles of the feet. Skin lesions stop at the lateral surfaces of the palms of the hands and/or the soles of the feet. In most cases, affected individuals also exhibit excessive sweating (hyperhidrosis) and unusually-shaped, thick nails. Most cases of this disorder are inherited as an autosomal dominant genetic trait; however, a severe autosomal recessive form has not been ruled out.
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Meleda Disease
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nord_786_5
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Diagnosis of Meleda Disease
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The diagnosis of Meleda disease may be confirmed by a thorough clinical evaluation that includes a detailed patient history and identification of characteristic physical findings. In most cases, skin abnormalities may be apparent at birth (congenital) or during infancy including characteristic skin abnormalities on the palms of the hands and the soles of the feet.
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Diagnosis of Meleda Disease. The diagnosis of Meleda disease may be confirmed by a thorough clinical evaluation that includes a detailed patient history and identification of characteristic physical findings. In most cases, skin abnormalities may be apparent at birth (congenital) or during infancy including characteristic skin abnormalities on the palms of the hands and the soles of the feet.
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Meleda Disease
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nord_786_6
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Therapies of Meleda Disease
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TreatmentThe treatment of Meleda 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, physicians who diagnose and treat skin problems (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Limited success has been found in treating associated skin lesions with lotions applied directly to the skin (topical). In some cases, surgery may be used to alleviate skin problems. Excessive sweating (hyperhidrosis) may be treated with aluminum acetate soaks or aluminum chloride hexahydrate applications.Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Therapies of Meleda Disease. TreatmentThe treatment of Meleda 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, physicians who diagnose and treat skin problems (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Limited success has been found in treating associated skin lesions with lotions applied directly to the skin (topical). In some cases, surgery may be used to alleviate skin problems. Excessive sweating (hyperhidrosis) may be treated with aluminum acetate soaks or aluminum chloride hexahydrate applications.Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Meleda Disease
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nord_787_0
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Overview of Melkersson-Rosenthal Syndrome
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SummaryMelkersson-Rosenthal syndrome (MRS) is a rare neurological disorder characterized by recurrent, long-lasting swelling of the face (edema), particularly of one or both lips (granulomatous cheilitis), facial muscle weakness (palsy) and deep grooves on the tongue (fissured tongue). Most affected individuals will have only one or two symptoms, while some may present with all three. MRS can affect individuals of all ages. The onset of symptoms is more frequent in young adulthood, but can occur well into adulthood. It is estimated that MRS occurs in 0.08% of the general population. There is no cure for MRS, but symptoms can be treated with anti-inflammatory agents, antihistamines, corticosteroids and in some cases surgery.
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Overview of Melkersson-Rosenthal Syndrome. SummaryMelkersson-Rosenthal syndrome (MRS) is a rare neurological disorder characterized by recurrent, long-lasting swelling of the face (edema), particularly of one or both lips (granulomatous cheilitis), facial muscle weakness (palsy) and deep grooves on the tongue (fissured tongue). Most affected individuals will have only one or two symptoms, while some may present with all three. MRS can affect individuals of all ages. The onset of symptoms is more frequent in young adulthood, but can occur well into adulthood. It is estimated that MRS occurs in 0.08% of the general population. There is no cure for MRS, but symptoms can be treated with anti-inflammatory agents, antihistamines, corticosteroids and in some cases surgery.
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Melkersson-Rosenthal Syndrome
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nord_787_1
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Symptoms of Melkersson-Rosenthal Syndrome
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Melkersson-Rosenthal syndrome is defined by recurrent swelling (edema) of various facial features such as the upper lip, lower lip, one or both cheeks, eyelids, or rarely, one side of the scalp. It is also characterized by recurrent muscle weakness or paralysis (palsy) in the face and deep grooves or cracks (fissures) in the tongue. Affected individuals usually present with only one or two symptoms. It is estimated that about 8-18% of all patients present with all three symptoms. The first episode of edema may resolve in a few hours or days, but swelling may be more severe and last longer in subsequent episodes and in some people can become permanent. The enlarged lips may appear cracked and discolored and can be painful. The edema resembles angioedema; rapid swelling caused by an accumulation of fluid, but tends to be more persistent and resistant to antihistamine treatment. Edema associated with MRS may also lead to the development of scar tissue (fibrosis) of the affected tissues. Edema is the most common feature, is often considered the characteristic symptom of MRS and may be the first or only symptom present. A fissured tongue is defined as grooves on the tongue measuring about 2mm (0.07 in) deep and 15mm (0.6 in) long. A fissured tongue is seen in 30-80% of those affected by MRS and may be present at birth. It may lead to secondary infections, enlargement (hypertrophy) of the tongue, loss of taste buds, or an itching/burning sensation (dysesthesia). Salivary gland secretion may also be reduced. Although associated with MRS, a fissured tongue is also present in about 0.5-5% of the general population and may be familial or hereditary. Facial muscle weakness and paralysis (facial palsy) occurs in 30-90% of those affected with MRS. It usually occurs after the first few episodes of edema but it can sometimes be the first and only symptom. In 13-50% of affected individuals, facial palsy is associated with facial edema. The facial weakness or paralysis can be on one side (unilateral) or both (bilateral) and resolves initially, but can become permanent. As the disease progresses, the duration of facial palsy may increase. Some individuals may also experience paralysis of other muscles in the head and neck associated with different cranial nerves. Children with recurrent facial palsy should be evaluated for underlying MRS. Recurrent facial palsy is observed in about 10% of all people with MRS. Individuals affected by MRS have also reported additional symptoms that include migraines, headaches, tinnitus or sudden deafness, dizziness, dry mouth, facial pain, difficulty swallowing, dry eyes, blurred vision, diarrhea, and excessive tearing. Non-neurological symptoms of MRS may also include inflammation of the intestines (diverticulitis) and inflammation of the eyes (uveitis).
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Symptoms of Melkersson-Rosenthal Syndrome. Melkersson-Rosenthal syndrome is defined by recurrent swelling (edema) of various facial features such as the upper lip, lower lip, one or both cheeks, eyelids, or rarely, one side of the scalp. It is also characterized by recurrent muscle weakness or paralysis (palsy) in the face and deep grooves or cracks (fissures) in the tongue. Affected individuals usually present with only one or two symptoms. It is estimated that about 8-18% of all patients present with all three symptoms. The first episode of edema may resolve in a few hours or days, but swelling may be more severe and last longer in subsequent episodes and in some people can become permanent. The enlarged lips may appear cracked and discolored and can be painful. The edema resembles angioedema; rapid swelling caused by an accumulation of fluid, but tends to be more persistent and resistant to antihistamine treatment. Edema associated with MRS may also lead to the development of scar tissue (fibrosis) of the affected tissues. Edema is the most common feature, is often considered the characteristic symptom of MRS and may be the first or only symptom present. A fissured tongue is defined as grooves on the tongue measuring about 2mm (0.07 in) deep and 15mm (0.6 in) long. A fissured tongue is seen in 30-80% of those affected by MRS and may be present at birth. It may lead to secondary infections, enlargement (hypertrophy) of the tongue, loss of taste buds, or an itching/burning sensation (dysesthesia). Salivary gland secretion may also be reduced. Although associated with MRS, a fissured tongue is also present in about 0.5-5% of the general population and may be familial or hereditary. Facial muscle weakness and paralysis (facial palsy) occurs in 30-90% of those affected with MRS. It usually occurs after the first few episodes of edema but it can sometimes be the first and only symptom. In 13-50% of affected individuals, facial palsy is associated with facial edema. The facial weakness or paralysis can be on one side (unilateral) or both (bilateral) and resolves initially, but can become permanent. As the disease progresses, the duration of facial palsy may increase. Some individuals may also experience paralysis of other muscles in the head and neck associated with different cranial nerves. Children with recurrent facial palsy should be evaluated for underlying MRS. Recurrent facial palsy is observed in about 10% of all people with MRS. Individuals affected by MRS have also reported additional symptoms that include migraines, headaches, tinnitus or sudden deafness, dizziness, dry mouth, facial pain, difficulty swallowing, dry eyes, blurred vision, diarrhea, and excessive tearing. Non-neurological symptoms of MRS may also include inflammation of the intestines (diverticulitis) and inflammation of the eyes (uveitis).
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Melkersson-Rosenthal Syndrome
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nord_787_2
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Causes of Melkersson-Rosenthal Syndrome
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The cause of MRS is still not known. Some cases of MRS have been attributed with various infections by bacterial or viral agents; it is possible that infection with herpesviruses may be a possible cause for MRS. Dietary and other allergens may also be involved in the development of MRS. Some studies have demonstrated the role of hormonal changes triggering the onset of inflammatory episodes. It is also suspected that MRS may be a secondary symptom of another condition such as Crohn’s disease or sarcoidosis. However, no strong associations exist to explain what causes MRS.There is evidence to suggest that MRS may be inherited because familial inheritance was observed in several patients. However, the presentation of symptoms is highly variable, which makes diagnosis and observing inheritance challenging. While genetics is suspected to be involved, changes (mutations) in specific genes have not been shown to cause the condition. Some reports have implicated several genes to be associated with MRS, but the majority of literature demonstrates that this condition is both clinically and genetically variable.
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Causes of Melkersson-Rosenthal Syndrome. The cause of MRS is still not known. Some cases of MRS have been attributed with various infections by bacterial or viral agents; it is possible that infection with herpesviruses may be a possible cause for MRS. Dietary and other allergens may also be involved in the development of MRS. Some studies have demonstrated the role of hormonal changes triggering the onset of inflammatory episodes. It is also suspected that MRS may be a secondary symptom of another condition such as Crohn’s disease or sarcoidosis. However, no strong associations exist to explain what causes MRS.There is evidence to suggest that MRS may be inherited because familial inheritance was observed in several patients. However, the presentation of symptoms is highly variable, which makes diagnosis and observing inheritance challenging. While genetics is suspected to be involved, changes (mutations) in specific genes have not been shown to cause the condition. Some reports have implicated several genes to be associated with MRS, but the majority of literature demonstrates that this condition is both clinically and genetically variable.
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Melkersson-Rosenthal Syndrome
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nord_787_3
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Affects of Melkersson-Rosenthal Syndrome
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MRS affects individuals of all ages. Typically, onset of symptoms begins in young adulthood but can occur well into adulthood. While it is not common, a few patients have been diagnosed during childhood. Most literature suggests that MRS tends to affect more females than males. Due to the rarity of MRS, accurate data regarding the incidence of this condition is difficult to obtain. It is likely an under-diagnosed condition as many people with MRS are misdiagnosed because the clinical symptoms overlap with many other common conditions.
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Affects of Melkersson-Rosenthal Syndrome. MRS affects individuals of all ages. Typically, onset of symptoms begins in young adulthood but can occur well into adulthood. While it is not common, a few patients have been diagnosed during childhood. Most literature suggests that MRS tends to affect more females than males. Due to the rarity of MRS, accurate data regarding the incidence of this condition is difficult to obtain. It is likely an under-diagnosed condition as many people with MRS are misdiagnosed because the clinical symptoms overlap with many other common conditions.
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Melkersson-Rosenthal Syndrome
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nord_787_4
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Related disorders of Melkersson-Rosenthal Syndrome
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Bell’s palsy is a nonprogressive neurological disorder of one of the facial nerves (7th cranial nerve). This disorder is characterized by the sudden onset of facial paralysis that may be preceded by a slight fever, pain behind the ear on the affected side, a stiff neck, and weakness and/or stiffness on one side of the face. Paralysis results from decreased blood supply (ischemia) and/or compression of the 7th cranial nerve. The exact cause of Bell’s palsy is not known. Viral (e.g., herpes zoster virus) and immune disorders are frequently implicated as a cause for this disorder. There may also be an inherited tendency toward developing Bell’s palsy. (For more information on this disorder, choose “Bell” as your search term in the Rare Disease Database). Crohn’s disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. The lower portion of the small intestine (ileum) and the rectum are most commonly affected by this disorder. Symptoms may include watery diarrhea, abdominal pain, fever, and weight loss. Some cases of Crohn’s disease can affect the mouth and lead to swelling of the lips and face, in addition to the gastrointestinal manifestations. The symptoms of Crohn’s disease can be difficult to manage and proper diagnosis is often delayed. The exact cause of Crohn’s disease is unknown. Sarcoidosis is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) consisting of certain granular white blood cells (modified macrophages or epithelioid cells) in certain organs of the body. The granulomas that are formed are thought to alter the normal structure of and, potentially, the normal functions of the affected organs. Granuloma formation most commonly affects the lungs; however, the upper respiratory system, lymph nodes, skin, and/or eyes may be involved. Other organs may also be affected, including the liver, bone marrow, spleen, musculoskeletal system, heart, salivary glands, and/or nervous system (i.e., central or peripheral nervous system).
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Related disorders of Melkersson-Rosenthal Syndrome. Bell’s palsy is a nonprogressive neurological disorder of one of the facial nerves (7th cranial nerve). This disorder is characterized by the sudden onset of facial paralysis that may be preceded by a slight fever, pain behind the ear on the affected side, a stiff neck, and weakness and/or stiffness on one side of the face. Paralysis results from decreased blood supply (ischemia) and/or compression of the 7th cranial nerve. The exact cause of Bell’s palsy is not known. Viral (e.g., herpes zoster virus) and immune disorders are frequently implicated as a cause for this disorder. There may also be an inherited tendency toward developing Bell’s palsy. (For more information on this disorder, choose “Bell” as your search term in the Rare Disease Database). Crohn’s disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. The lower portion of the small intestine (ileum) and the rectum are most commonly affected by this disorder. Symptoms may include watery diarrhea, abdominal pain, fever, and weight loss. Some cases of Crohn’s disease can affect the mouth and lead to swelling of the lips and face, in addition to the gastrointestinal manifestations. The symptoms of Crohn’s disease can be difficult to manage and proper diagnosis is often delayed. The exact cause of Crohn’s disease is unknown. Sarcoidosis is characterized by the abnormal formation of inflammatory masses or nodules (granulomas) consisting of certain granular white blood cells (modified macrophages or epithelioid cells) in certain organs of the body. The granulomas that are formed are thought to alter the normal structure of and, potentially, the normal functions of the affected organs. Granuloma formation most commonly affects the lungs; however, the upper respiratory system, lymph nodes, skin, and/or eyes may be involved. Other organs may also be affected, including the liver, bone marrow, spleen, musculoskeletal system, heart, salivary glands, and/or nervous system (i.e., central or peripheral nervous system).
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Melkersson-Rosenthal Syndrome
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Diagnosis of Melkersson-Rosenthal Syndrome
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MRS is diagnosed clinically, based on physical findings and medical history. The presence of persistent or recurrent facial swelling and either facial palsy or tongue findings may be sufficient for a clinical diagnosis. A biopsy of the lips may be necessary to confirm the diagnosis and rule out possible infectious causes, recurrent angioedema, Crohn’s disease, sarcoidosis or cancers. The presence of only one of the clinical features is enough for diagnosis when a biopsy of affected tissues is consistent with MRS. Because of the overlapping features of MRS with other common conditions, time to diagnosis may take years. Clinical Testing and Work-Up
The symptoms of MRShave significant overlap with common conditions and initial evaluation may involve specialized laboratory studies and procedures to rule out Crohn’s disease and sarcoidosis. When there is a suspected diagnosis of MRS, it is recommended to follow up with dermatology, immunology, gastroenterology, and ophthalmology to rule out other conditions with similar clinical presentations.
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Diagnosis of Melkersson-Rosenthal Syndrome. MRS is diagnosed clinically, based on physical findings and medical history. The presence of persistent or recurrent facial swelling and either facial palsy or tongue findings may be sufficient for a clinical diagnosis. A biopsy of the lips may be necessary to confirm the diagnosis and rule out possible infectious causes, recurrent angioedema, Crohn’s disease, sarcoidosis or cancers. The presence of only one of the clinical features is enough for diagnosis when a biopsy of affected tissues is consistent with MRS. Because of the overlapping features of MRS with other common conditions, time to diagnosis may take years. Clinical Testing and Work-Up
The symptoms of MRShave significant overlap with common conditions and initial evaluation may involve specialized laboratory studies and procedures to rule out Crohn’s disease and sarcoidosis. When there is a suspected diagnosis of MRS, it is recommended to follow up with dermatology, immunology, gastroenterology, and ophthalmology to rule out other conditions with similar clinical presentations.
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Melkersson-Rosenthal Syndrome
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Therapies of Melkersson-Rosenthal Syndrome
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Treatment
There is no standard method of treatment for MRS. Most signs and symptoms of MRS resolve without treatment but episodes may occur more often and last longer if the condition is not treated. Treatment for MRS may include corticosteroid injections, nonsteroidal anti-inflammatory agents, antihistamines, and antibiotics. In some patients, MRS may be treated with short courses of immunosuppressants. Surgery and/or radiation are sometimes recommended to reduce abnormally swollen lips. If patients experience persistent and recurrent facial paralysis, surgery may be required to decompress affected facial nerves.
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Therapies of Melkersson-Rosenthal Syndrome. Treatment
There is no standard method of treatment for MRS. Most signs and symptoms of MRS resolve without treatment but episodes may occur more often and last longer if the condition is not treated. Treatment for MRS may include corticosteroid injections, nonsteroidal anti-inflammatory agents, antihistamines, and antibiotics. In some patients, MRS may be treated with short courses of immunosuppressants. Surgery and/or radiation are sometimes recommended to reduce abnormally swollen lips. If patients experience persistent and recurrent facial paralysis, surgery may be required to decompress affected facial nerves.
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Melkersson-Rosenthal Syndrome
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Overview of Melnick Needles Syndrome
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SummaryMelnick-Needles syndrome (MNS) is a rare genetic disorder of bone characterized by skeletal and craniofacial abnormalities with a specific facial appearance. The skeletal abnormalities include bowing of long bones, s-curved leg bones, ribbon-like ribs and a hardening of the skull base, as well as spine deformities. The typical facial features include prominent, protruding eyes, full cheeks, an extremely small lower jaw and a hairy forehead. The condition may affect many bones of the body causing deformities and often short stature. Regular evaluations as well as surgical treatment may be needed to manage symptoms. MNS is thought to follow an X-linked dominant pattern of inheritance and is usually caused by a new change (mutation) in the FLNA gene.
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Overview of Melnick Needles Syndrome. SummaryMelnick-Needles syndrome (MNS) is a rare genetic disorder of bone characterized by skeletal and craniofacial abnormalities with a specific facial appearance. The skeletal abnormalities include bowing of long bones, s-curved leg bones, ribbon-like ribs and a hardening of the skull base, as well as spine deformities. The typical facial features include prominent, protruding eyes, full cheeks, an extremely small lower jaw and a hairy forehead. The condition may affect many bones of the body causing deformities and often short stature. Regular evaluations as well as surgical treatment may be needed to manage symptoms. MNS is thought to follow an X-linked dominant pattern of inheritance and is usually caused by a new change (mutation) in the FLNA gene.
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Melnick Needles Syndrome
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Symptoms of Melnick Needles Syndrome
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MNS is a congenital condition, meaning it is present from birth. However, different members of the same family can have differences in the severity of their symptoms. Due to this variability, individuals may vary in their age at the time of diagnosis. Individuals with MNS have a particular facial appearance with prominent, widely spaced eyes (hypertelorism), full cheeks, small facial bones and an unusually small lower jaw (micrognathia). The skull may be slow to develop and the way in which individuals with MNS bring their teeth together (bite) may be abnormal. They may also have misaligned teeth or a partial absence of teeth (oligodontia).The upper arms and the last bones in the fingers (distal phalanges) may be shorter than normal. One of the short bones of the arm (radius) and of the leg (fibula) may be bowed. The distal (farthest from the body) ends of the long bone of the arm (humerus) and of the two short bones of the leg (tibia, fibula) may be flared. The connection between the long bone of the leg (femur) and the hip may be misaligned (coxa valga), causing an unusual walking pattern (gait).Individuals with MNS may also have a relatively small chest cavity (thoracic cage) with irregular ribbon-like ribs, a short collarbone (clavicle) and narrow shoulders. The lower part of their chest has a hollow shape (pectus excavatum). The vertebrae may be longer than normal. Spinal abnormalities, like an abnormal curvature of the spine (scoliosis), have been reported. Part of the pelvis (ilium) may also be flared. Short stature is often seen.Occasionally, dislocation of the hip may occur. Other abnormalities may also be noted. For example, the tube that runs from the kidney to the bladder (ureter) may be abnormally narrow, which can lead to urine retention and kidney problems. There may also be problems with heart structure (congenital heart defects) and high blood pressure in the lungs (pulmonary hypertension). Individuals with MNS may develop joint disease (osteoarthritis) in the back and/or hip in later years. The shape of the pelvis in females may make normal childbirth difficult for them. Individuals with MNS may be unusually susceptible to respiratory infections.Intellectual development is normal in individuals with MNS. Some individuals with MNS may have hearing loss.MNS is more severe and may be lethal in males. While it is lethal in most males during pregnancy or shortly after birth, there are case reports of males with typical features of MNS in their childhood-adolescent years. In these reports, the males were born to healthy parents and were the first in their families to show symptoms. Abnormalities seen in males with MNS include bulging eyes, protrusion of internal organs through the abdominal wall (omphalocele) and major skeletal abnormalities.
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Symptoms of Melnick Needles Syndrome. MNS is a congenital condition, meaning it is present from birth. However, different members of the same family can have differences in the severity of their symptoms. Due to this variability, individuals may vary in their age at the time of diagnosis. Individuals with MNS have a particular facial appearance with prominent, widely spaced eyes (hypertelorism), full cheeks, small facial bones and an unusually small lower jaw (micrognathia). The skull may be slow to develop and the way in which individuals with MNS bring their teeth together (bite) may be abnormal. They may also have misaligned teeth or a partial absence of teeth (oligodontia).The upper arms and the last bones in the fingers (distal phalanges) may be shorter than normal. One of the short bones of the arm (radius) and of the leg (fibula) may be bowed. The distal (farthest from the body) ends of the long bone of the arm (humerus) and of the two short bones of the leg (tibia, fibula) may be flared. The connection between the long bone of the leg (femur) and the hip may be misaligned (coxa valga), causing an unusual walking pattern (gait).Individuals with MNS may also have a relatively small chest cavity (thoracic cage) with irregular ribbon-like ribs, a short collarbone (clavicle) and narrow shoulders. The lower part of their chest has a hollow shape (pectus excavatum). The vertebrae may be longer than normal. Spinal abnormalities, like an abnormal curvature of the spine (scoliosis), have been reported. Part of the pelvis (ilium) may also be flared. Short stature is often seen.Occasionally, dislocation of the hip may occur. Other abnormalities may also be noted. For example, the tube that runs from the kidney to the bladder (ureter) may be abnormally narrow, which can lead to urine retention and kidney problems. There may also be problems with heart structure (congenital heart defects) and high blood pressure in the lungs (pulmonary hypertension). Individuals with MNS may develop joint disease (osteoarthritis) in the back and/or hip in later years. The shape of the pelvis in females may make normal childbirth difficult for them. Individuals with MNS may be unusually susceptible to respiratory infections.Intellectual development is normal in individuals with MNS. Some individuals with MNS may have hearing loss.MNS is more severe and may be lethal in males. While it is lethal in most males during pregnancy or shortly after birth, there are case reports of males with typical features of MNS in their childhood-adolescent years. In these reports, the males were born to healthy parents and were the first in their families to show symptoms. Abnormalities seen in males with MNS include bulging eyes, protrusion of internal organs through the abdominal wall (omphalocele) and major skeletal abnormalities.
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Melnick Needles Syndrome
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Causes of Melnick Needles Syndrome
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MNS is an X-linked dominant genetic disorder caused by an abnormality (mutation) in the FLNA gene which contains instructions for creating a protein called filamin A. The FLNA gene has been mapped to chromosome Xq28.Filamin A is an important part of the cell cytoskeleton, a network of proteins that gives cells structure and flexibility. Researchers believe that mutations which cause the FLNA gene to become overactive (gain of function) impact its role in skeletal development, but the exact mechanisms that lead to the symptoms seen in MNS are unknown. 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 subdivided into many bands that are numbered. For example, “chromosome Xq28” refers to band 28 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.X-linked dominant disorders are caused by a non-working gene on the X chromosome and occur mostly in females. Females with these rare conditions are affected when they have an X chromosome with the non-working gene for a particular disease. Males with a non-working gene for an X-linked dominant disorder are more severely affected than females and often do not survive.MNS usually occurs as the result of a new mutation in the FLNA gene that is not inherited, but familial inheritance has been noted in some families.
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Causes of Melnick Needles Syndrome. MNS is an X-linked dominant genetic disorder caused by an abnormality (mutation) in the FLNA gene which contains instructions for creating a protein called filamin A. The FLNA gene has been mapped to chromosome Xq28.Filamin A is an important part of the cell cytoskeleton, a network of proteins that gives cells structure and flexibility. Researchers believe that mutations which cause the FLNA gene to become overactive (gain of function) impact its role in skeletal development, but the exact mechanisms that lead to the symptoms seen in MNS are unknown. 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 subdivided into many bands that are numbered. For example, “chromosome Xq28” refers to band 28 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.X-linked dominant disorders are caused by a non-working gene on the X chromosome and occur mostly in females. Females with these rare conditions are affected when they have an X chromosome with the non-working gene for a particular disease. Males with a non-working gene for an X-linked dominant disorder are more severely affected than females and often do not survive.MNS usually occurs as the result of a new mutation in the FLNA gene that is not inherited, but familial inheritance has been noted in some families.
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Melnick Needles Syndrome
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Affects of Melnick Needles Syndrome
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MNS occurs in females much more often than in males. This is because males with MNS often do not survive to term in pregnancy. Approximately 70 total cases have been reported in the medical literature, but it is likely that there are many more individuals with MNS who haven’t been reported in the medical literature or haven’t been diagnosed.
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Affects of Melnick Needles Syndrome. MNS occurs in females much more often than in males. This is because males with MNS often do not survive to term in pregnancy. Approximately 70 total cases have been reported in the medical literature, but it is likely that there are many more individuals with MNS who haven’t been reported in the medical literature or haven’t been diagnosed.
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Melnick Needles Syndrome
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Related disorders of Melnick Needles Syndrome
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Symptoms of the following disorders can be similar to those of Melnick-Needles syndrome. Comparisons may be useful for a differential diagnosis:Multiple epiphyseal dysplasia (MED) is a hereditary bone disorder that affects females and males in equal numbers. It can either have an autosomal recessive or autosomal dominant pattern of inheritance. Symptoms begin between two and five years of age with the appearance of a waddling gait. Individuals with MED may experience pain because of joint disease (osteoarthritis). Body size tends to be almost normal, except for the hands and feet which are disproportionately small. (For more information on this condition, choose “rMED or dMED” as your search terms in the Rare Disease Database.)Otopalatodigital syndrome type 2 (OPD2) is an X-linked disorder that involves skeletal abnormalities and a particular facial appearance. Like MNS, it is more severe and often lethal in males. However, females with OPD2 typically have milder features in comparison to those with Melnick-Needles syndrome. (For more information on this condition, choose “otopalatodigital syndrome” as your search term in the Rare Disease Database.) Frank Ter Haar syndrome is an autosomal recessive disorder that also involves skeletal abnormalities, congenital heart defects and a particular facial appearance. It was previously thought to be a form of Melnick-Needles syndrome. However, it affects females and males in equal numbers. Shprintzen-Goldberg syndrome (SGS) is a rare connective tissue disorder that affects females and males in equal numbers. It has an autosomal dominant pattern of inheritance. Individuals with SGS have similar skeletal features, particularly in the vertebrae, but they have differences in the fusion of skull bones (craniosynostosis) and intellectual disability not generally seen in Melnick-Needles syndrome. (For more information on this condition, choose “Shprintzen Goldberg syndrome” as your search term in the Rare Disease Database.)
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Related disorders of Melnick Needles Syndrome. Symptoms of the following disorders can be similar to those of Melnick-Needles syndrome. Comparisons may be useful for a differential diagnosis:Multiple epiphyseal dysplasia (MED) is a hereditary bone disorder that affects females and males in equal numbers. It can either have an autosomal recessive or autosomal dominant pattern of inheritance. Symptoms begin between two and five years of age with the appearance of a waddling gait. Individuals with MED may experience pain because of joint disease (osteoarthritis). Body size tends to be almost normal, except for the hands and feet which are disproportionately small. (For more information on this condition, choose “rMED or dMED” as your search terms in the Rare Disease Database.)Otopalatodigital syndrome type 2 (OPD2) is an X-linked disorder that involves skeletal abnormalities and a particular facial appearance. Like MNS, it is more severe and often lethal in males. However, females with OPD2 typically have milder features in comparison to those with Melnick-Needles syndrome. (For more information on this condition, choose “otopalatodigital syndrome” as your search term in the Rare Disease Database.) Frank Ter Haar syndrome is an autosomal recessive disorder that also involves skeletal abnormalities, congenital heart defects and a particular facial appearance. It was previously thought to be a form of Melnick-Needles syndrome. However, it affects females and males in equal numbers. Shprintzen-Goldberg syndrome (SGS) is a rare connective tissue disorder that affects females and males in equal numbers. It has an autosomal dominant pattern of inheritance. Individuals with SGS have similar skeletal features, particularly in the vertebrae, but they have differences in the fusion of skull bones (craniosynostosis) and intellectual disability not generally seen in Melnick-Needles syndrome. (For more information on this condition, choose “Shprintzen Goldberg syndrome” as your search term in the Rare Disease Database.)
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Melnick Needles Syndrome
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Diagnosis of Melnick Needles Syndrome
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MNS is diagnosed through clinical and radiographic (ex: X-ray) evaluation and/or molecular genetic testing of the FLNA gene. A positive family history showing X-linked inheritance can also aid in the diagnosis. Males with MNS typically have clinical features similar to otopalatodigital syndrome type 2. Females with MNS present with significant clinical variability. Some individuals with MNS may show no or few symptoms and are diagnosed in adulthood after learning about an affected relative, whereas others may be diagnosed before or shortly after birth.If a mother has a known disease-causing (pathogenic) variant in the FLNA gene, a pregnancy can be diagnosed via chorionic villus sampling (CVS) or amniocentesis. Both procedures are invasive and examine fetal DNA to confirm a prenatal diagnosis but differ in timing regarding when they are offered during the pregnancy. Prenatal ultrasounds may be able to detect physical features suggestive of MNS, but molecular genetic testing is required to confirm a diagnosis.
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Diagnosis of Melnick Needles Syndrome. MNS is diagnosed through clinical and radiographic (ex: X-ray) evaluation and/or molecular genetic testing of the FLNA gene. A positive family history showing X-linked inheritance can also aid in the diagnosis. Males with MNS typically have clinical features similar to otopalatodigital syndrome type 2. Females with MNS present with significant clinical variability. Some individuals with MNS may show no or few symptoms and are diagnosed in adulthood after learning about an affected relative, whereas others may be diagnosed before or shortly after birth.If a mother has a known disease-causing (pathogenic) variant in the FLNA gene, a pregnancy can be diagnosed via chorionic villus sampling (CVS) or amniocentesis. Both procedures are invasive and examine fetal DNA to confirm a prenatal diagnosis but differ in timing regarding when they are offered during the pregnancy. Prenatal ultrasounds may be able to detect physical features suggestive of MNS, but molecular genetic testing is required to confirm a diagnosis.
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Melnick Needles Syndrome
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Therapies of Melnick Needles Syndrome
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TreatmentTreatment of MNS is based on addressing individual symptoms. Clinical care can involve multiple specialists, such as orthopedics, cardiology, audiology, dentistry, surgery and nephrology. There is currently no cure for MNS.Genetic counseling is recommended for patients and their families.
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Therapies of Melnick Needles Syndrome. TreatmentTreatment of MNS is based on addressing individual symptoms. Clinical care can involve multiple specialists, such as orthopedics, cardiology, audiology, dentistry, surgery and nephrology. There is currently no cure for MNS.Genetic counseling is recommended for patients and their families.
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Melnick Needles Syndrome
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Overview of Melorheostosis
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Melorheostosis is a rare and progressive disease characterized by thickening or widening (hyperostosis) of the outer layers of the bone (cortical bone). Melorheostosis affects both bone and soft tissue growth and development. This disorder is benign (noncancerous), but it often results in severe functional limitation; chronic pain; joint contractures and/or stiff muscles, tendons or ligaments; and limb, hand, or foot deformities.
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Overview of Melorheostosis. Melorheostosis is a rare and progressive disease characterized by thickening or widening (hyperostosis) of the outer layers of the bone (cortical bone). Melorheostosis affects both bone and soft tissue growth and development. This disorder is benign (noncancerous), but it often results in severe functional limitation; chronic pain; joint contractures and/or stiff muscles, tendons or ligaments; and limb, hand, or foot deformities.
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Melorheostosis
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Symptoms of Melorheostosis
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Signs and symptoms of melorheostosis include irregular bone growth, including cortical thickening and “dripping candle wax” appearance on x-ray imaging; unequal length of limbs; soft tissue abnormalities, including tendon and ligament shortening, absent or abnormal muscles, subcutaneous calcification, joint swelling and contractures resulting in malformed or immobilized joints; range of motion limitations; pain and stiffness; limb swelling (edema) and vascular abnormalities. Less commonly, but severe, the bone lesions may compress the surrounding nerves.Melorheostosis usually affects one particular segment of the appendicular skeleton (arms and legs). It is usually limited to one side of the body (rarely bilateral) and within a limb restricted to either the medial or lateral side of the bones. The disease can also affect the axial skeleton: pelvis, sternum, ribs and, more rarely, the spine and skull. Symptoms may progressively worsen over time.In children, the condition usually presents with limb length inequality, deformity, or joint contractures. In adults, symptoms of pain, joint stiffness, and progressive deformity are more apparent.The age of diagnosis is typically based on severity of onset and symptoms and varies widely in children and adults. Melorheostosis is usually observed in early childhood and may even be apparent in the first days of life. Fifty percent of patients with melorheostosis will develop symptoms by age 20.
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Symptoms of Melorheostosis. Signs and symptoms of melorheostosis include irregular bone growth, including cortical thickening and “dripping candle wax” appearance on x-ray imaging; unequal length of limbs; soft tissue abnormalities, including tendon and ligament shortening, absent or abnormal muscles, subcutaneous calcification, joint swelling and contractures resulting in malformed or immobilized joints; range of motion limitations; pain and stiffness; limb swelling (edema) and vascular abnormalities. Less commonly, but severe, the bone lesions may compress the surrounding nerves.Melorheostosis usually affects one particular segment of the appendicular skeleton (arms and legs). It is usually limited to one side of the body (rarely bilateral) and within a limb restricted to either the medial or lateral side of the bones. The disease can also affect the axial skeleton: pelvis, sternum, ribs and, more rarely, the spine and skull. Symptoms may progressively worsen over time.In children, the condition usually presents with limb length inequality, deformity, or joint contractures. In adults, symptoms of pain, joint stiffness, and progressive deformity are more apparent.The age of diagnosis is typically based on severity of onset and symptoms and varies widely in children and adults. Melorheostosis is usually observed in early childhood and may even be apparent in the first days of life. Fifty percent of patients with melorheostosis will develop symptoms by age 20.
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Melorheostosis
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Causes of Melorheostosis
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Melorheostosis is usually an isolated disorder. However, it has also been observed in a few families with osteopoikilosis or the Buschke- Ollendorff syndrome due to a change (mutation) in the LEMD3 gene. The sporadic occurrence of the disorder with no reports of parent to child transmission and the localized distribution of bone lesions led to the hypothesis that a somatic mutation may be responsible for the disease. This hypothesis was recently proven by the identification of somatic mutations in the MAP2K1 gene and the SMAD3 gene. There is also indication that somatic mutations in other, yet unknown, genes may be responsible for the disorder. Somatic mutations are changes in DNA that occur after conception, so they are not present in egg or sperm cells and are not passed down in families.
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Causes of Melorheostosis. Melorheostosis is usually an isolated disorder. However, it has also been observed in a few families with osteopoikilosis or the Buschke- Ollendorff syndrome due to a change (mutation) in the LEMD3 gene. The sporadic occurrence of the disorder with no reports of parent to child transmission and the localized distribution of bone lesions led to the hypothesis that a somatic mutation may be responsible for the disease. This hypothesis was recently proven by the identification of somatic mutations in the MAP2K1 gene and the SMAD3 gene. There is also indication that somatic mutations in other, yet unknown, genes may be responsible for the disorder. Somatic mutations are changes in DNA that occur after conception, so they are not present in egg or sperm cells and are not passed down in families.
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Melorheostosis
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Affects of Melorheostosis
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The estimated incidence of melorheostosis is 1 in 1,000,000. Males and females are affected and approximately 400 cases have been reported.
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Affects of Melorheostosis. The estimated incidence of melorheostosis is 1 in 1,000,000. Males and females are affected and approximately 400 cases have been reported.
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Melorheostosis
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Related disorders of Melorheostosis
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Symptoms of the following disorders can be similar to those of melorheostosis. Comparison may be useful for a differential diagnosis:Osteopoikilosis is a rare and benign bone disorder characterized by multiple round or oval areas of increased bone density at the ends of the long bones. They are usually present on both sides (bilaterally) of the body.Buschke-Ollendorff syndrome is a rare hereditary disorder of connective tissue characterized by the combination of skin growths (called connective tissue nevi) with osteopoikilosis.Osteopathia striata is a benign bone disorder characterized by longitudinal “stripes” of increased density in affected bones.Linear scleroderma appears as a band-like thickening of skin on the arms and legs. It typically appears first during early childhood and is characterized by the failure of one limb to grow as rapidly as its counterpart.Desmoid tumors commonly develop in the fibrous (connective) tissue of the body that forms tendons and ligaments, usually in the arms, legs or midsection, and also in the head and neck. Desmoid tumors can be invasive to surrounding tissues and difficult to control. (For more information on this disorder, choose “desmoid tumor” as your search term in the Rare Disease Database.)Hemangiomas appear in early infancy and are growths made up of small blood vessels.
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Related disorders of Melorheostosis. Symptoms of the following disorders can be similar to those of melorheostosis. Comparison may be useful for a differential diagnosis:Osteopoikilosis is a rare and benign bone disorder characterized by multiple round or oval areas of increased bone density at the ends of the long bones. They are usually present on both sides (bilaterally) of the body.Buschke-Ollendorff syndrome is a rare hereditary disorder of connective tissue characterized by the combination of skin growths (called connective tissue nevi) with osteopoikilosis.Osteopathia striata is a benign bone disorder characterized by longitudinal “stripes” of increased density in affected bones.Linear scleroderma appears as a band-like thickening of skin on the arms and legs. It typically appears first during early childhood and is characterized by the failure of one limb to grow as rapidly as its counterpart.Desmoid tumors commonly develop in the fibrous (connective) tissue of the body that forms tendons and ligaments, usually in the arms, legs or midsection, and also in the head and neck. Desmoid tumors can be invasive to surrounding tissues and difficult to control. (For more information on this disorder, choose “desmoid tumor” as your search term in the Rare Disease Database.)Hemangiomas appear in early infancy and are growths made up of small blood vessels.
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Melorheostosis
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Diagnosis of Melorheostosis
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In melorheostosis, bone scans appear to be markedly positive. However, on magnetic resonance imaging (MRI) there is usually a low signal. X-ray imaging is the preferred diagnostic tool for melorheostosis. X-rays often reveal a pattern of thickened bone (sclerotic bone lesions) that resembles dripping candle wax.
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Diagnosis of Melorheostosis. In melorheostosis, bone scans appear to be markedly positive. However, on magnetic resonance imaging (MRI) there is usually a low signal. X-ray imaging is the preferred diagnostic tool for melorheostosis. X-rays often reveal a pattern of thickened bone (sclerotic bone lesions) that resembles dripping candle wax.
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Melorheostosis
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Therapies of Melorheostosis
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TreatmentTreatments are limited at the present time and are predominantly aimed at reducing symptoms. No treatment option has been found to be fully effective, and what may be helpful to one person may be ineffective or even detrimental to another. Treatment options may include surgery, physical and occupational therapy, hydrotherapy, and medications to alter the bone remodeling process.Pain management may be challenging. Medications prescribed for pain may include non-steroidal anti-inflammatory drugs (NSAIDs), steroids or rarely narcotics. These medications are sometimes helpful in the early stages of the chronic progression of the disease but may be less so for the severely affected. However, some patients have shown benefit in either symptoms or on bone scans.
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Therapies of Melorheostosis. TreatmentTreatments are limited at the present time and are predominantly aimed at reducing symptoms. No treatment option has been found to be fully effective, and what may be helpful to one person may be ineffective or even detrimental to another. Treatment options may include surgery, physical and occupational therapy, hydrotherapy, and medications to alter the bone remodeling process.Pain management may be challenging. Medications prescribed for pain may include non-steroidal anti-inflammatory drugs (NSAIDs), steroids or rarely narcotics. These medications are sometimes helpful in the early stages of the chronic progression of the disease but may be less so for the severely affected. However, some patients have shown benefit in either symptoms or on bone scans.
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Overview of Menetrier Disease
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Menetrier disease is a rare disorder characterized by massive overgrowth of mucous cells (foveola) in the mucous membrane lining the stomach, resulting in large gastric folds. The most common symptom associated with Menetrier disease is pain in the upper middle region of the stomach (epigastric pain). The cause of Menetrier disease is unknown.There is considerable confusion and contradiction in the medical literature regarding disorders involving large gastric folds. The name Menetrier disease is often erroneously used to describe any condition with large gastric folds or as a synonym for giant hypertrophic gastritis (GHG). However, Menetrier disease is not a true form of gastritis. A diagnosis of Menetrier disease should be reserved for individuals with large gastric folds due to overgrowth of mucous cells. There is minimal or no stomach inflammation in Menetrier disease. Because inflammation is minimal or not present, Menetrier disease is classified as a form of hyperplastic gastropathy and not as a form of gastritis. Some researchers believe that Menetrier disease and GHG may be variants of the same disorder or different parts of one disease spectrum.
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Overview of Menetrier Disease. Menetrier disease is a rare disorder characterized by massive overgrowth of mucous cells (foveola) in the mucous membrane lining the stomach, resulting in large gastric folds. The most common symptom associated with Menetrier disease is pain in the upper middle region of the stomach (epigastric pain). The cause of Menetrier disease is unknown.There is considerable confusion and contradiction in the medical literature regarding disorders involving large gastric folds. The name Menetrier disease is often erroneously used to describe any condition with large gastric folds or as a synonym for giant hypertrophic gastritis (GHG). However, Menetrier disease is not a true form of gastritis. A diagnosis of Menetrier disease should be reserved for individuals with large gastric folds due to overgrowth of mucous cells. There is minimal or no stomach inflammation in Menetrier disease. Because inflammation is minimal or not present, Menetrier disease is classified as a form of hyperplastic gastropathy and not as a form of gastritis. Some researchers believe that Menetrier disease and GHG may be variants of the same disorder or different parts of one disease spectrum.
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Symptoms of Menetrier Disease
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The symptoms of Menetrier disease may vary from case to case. Some individuals may not exhibit any symptoms (asymptomatic). The most common symptom is pain in the upper middle region of the stomach (epigastric pain). Less frequent reported symptoms include nausea, vomiting, and diarrhea. In some cases, weight loss and profound loss of appetite (anorexia) may also occur.An additional variable finding sometimes associated with Menetrier disease is the loss of protein from the circulation into the gastrointestinal tract (protein-losing gastropathy) such as the loss of the protein albumin (hypoalbuminemia). Protein loss may be severe in some cases. Protein loss may result in fluid accumulation (edema), especially in the legs.Gastrointestinal bleeding has also been reported in some cases of Menetrier disease usually as a result of erosions or ulcers in the stomach lining. Acid secretion by the stomach is often markedly decreased (hypochlorhydria) or absent. Excess mucous secretion in the stomach may also occur.Some researchers believe that individuals with Menetrier disease have a greater risk of developing gastric cancer than the general population has. However, other researchers do not believe this to be proven with certainty. In some series, there has been an association between Menetrier disease and ulcerative colitis.
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Symptoms of Menetrier Disease. The symptoms of Menetrier disease may vary from case to case. Some individuals may not exhibit any symptoms (asymptomatic). The most common symptom is pain in the upper middle region of the stomach (epigastric pain). Less frequent reported symptoms include nausea, vomiting, and diarrhea. In some cases, weight loss and profound loss of appetite (anorexia) may also occur.An additional variable finding sometimes associated with Menetrier disease is the loss of protein from the circulation into the gastrointestinal tract (protein-losing gastropathy) such as the loss of the protein albumin (hypoalbuminemia). Protein loss may be severe in some cases. Protein loss may result in fluid accumulation (edema), especially in the legs.Gastrointestinal bleeding has also been reported in some cases of Menetrier disease usually as a result of erosions or ulcers in the stomach lining. Acid secretion by the stomach is often markedly decreased (hypochlorhydria) or absent. Excess mucous secretion in the stomach may also occur.Some researchers believe that individuals with Menetrier disease have a greater risk of developing gastric cancer than the general population has. However, other researchers do not believe this to be proven with certainty. In some series, there has been an association between Menetrier disease and ulcerative colitis.
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Causes of Menetrier Disease
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The exact cause of Menetrier disease is unknown. There may be multiple causes. In children, some cases of Menetrier disease may be associated with infection with cytomegalovirus (CMV). The bacterium Helicobacter pylori has been implicated in some adults with Menetrier disease. The exact role, if any that these infections play in the development of Menetrier disease is unknown.Some researchers believe that the large gastric folds that characterize Menetrier disease may result from increased activation of the epidermal growth factor receptor in the stomach by a protein called transforming growth factor-alpha (TGF).In extremely rare cases, siblings of affected patients have developed Menetrier disease as children suggesting a genetic link in these cases. Researchers believe that, in these cases, Menetrier disease may be inherited as an autosomal dominant trait. Genetic diseases are determined by two sets of genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
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Causes of Menetrier Disease. The exact cause of Menetrier disease is unknown. There may be multiple causes. In children, some cases of Menetrier disease may be associated with infection with cytomegalovirus (CMV). The bacterium Helicobacter pylori has been implicated in some adults with Menetrier disease. The exact role, if any that these infections play in the development of Menetrier disease is unknown.Some researchers believe that the large gastric folds that characterize Menetrier disease may result from increased activation of the epidermal growth factor receptor in the stomach by a protein called transforming growth factor-alpha (TGF).In extremely rare cases, siblings of affected patients have developed Menetrier disease as children suggesting a genetic link in these cases. Researchers believe that, in these cases, Menetrier disease may be inherited as an autosomal dominant trait. Genetic diseases are determined by two sets of genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
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Affects of Menetrier Disease
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Menetrier disease affects males slightly more often than females. It most often affects adults in their 50s or older. However, a childhood form of the disorder exists. Because of the confusion in the literature regarding the term Menetrier disease, it is difficult to determine its true frequency in the general population.
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Affects of Menetrier Disease. Menetrier disease affects males slightly more often than females. It most often affects adults in their 50s or older. However, a childhood form of the disorder exists. Because of the confusion in the literature regarding the term Menetrier disease, it is difficult to determine its true frequency in the general population.
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Related disorders of Menetrier Disease
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Symptoms of the following disorders can be similar to those of Menetrier disease. Comparisons may be useful for a differential diagnosis:Zollinger-Ellison syndrome (ZES) is a rare, digestive disorder characterized by the development of a tumor (gastrinoma) or tumors that secrete excessive levels of gastrin, a hormone that stimulates production of acid by the stomach. Many affected individuals develop multiple gastrinomas, approximately half to two-thirds of which may be cancerous (malignant). In most cases, the tumors arise within the pancreas and/or the upper region of the small intestine (duodenum). Due to excessive acid production (gastric acid hypersecretion), individuals with ZES may develop peptic ulcers of the stomach, the duodenum, and/or other regions of the digestive tract. Peptic ulcers are sores or raw areas within the digestive tract where the lining has been eroded by stomach acid and digestive juices. Symptoms and findings associated with ZES may include mild to severe abdominal pain; diarrhea; gastroinestinal bleeding; increased amounts of fat in the stools (steatorrhea); and/or other abnormalities. Individuals with Zollinger-Ellison syndrome may have giant gastric folds. (For more information on this disorder, choose “Zollinger-Ellison” as your search term in the Rare Disease Database.)Lymphocytic gastritis is a rare disorder characterized by inflammation of the stomach due to the accumulation of inflammatory cells in the inner wall (mucosa) of the stomach resulting in abnormally large, coiled ridges or folds that resemble polyps in the inner wall of the stomach (large gastric folds). Many individuals with lymphocytic gastritis do not have symptoms (asymptomatic). Symptoms that may occur include nausea, vomiting, abdominal pain, diarrhea, and weight loss. The exact cause of lymphocytic gastritis is unknown although the disorder has been linked to celiac sprue and also to Helicobacter pylori infection. (For more information on this disorder, choose “lymphocytic gastritis” as your search term in the Rare Disease Database.)Additional causes of large gastric folds include Helicobacter pylori-associated gastritis, certain infections including syphilis, and various forms of cancer include certain forms of carcinoma or lymphoma. Other rare disorders such as sarcoidosis or Cronkite-Canada disease may also be associated with large gastric folds. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Related disorders of Menetrier Disease. Symptoms of the following disorders can be similar to those of Menetrier disease. Comparisons may be useful for a differential diagnosis:Zollinger-Ellison syndrome (ZES) is a rare, digestive disorder characterized by the development of a tumor (gastrinoma) or tumors that secrete excessive levels of gastrin, a hormone that stimulates production of acid by the stomach. Many affected individuals develop multiple gastrinomas, approximately half to two-thirds of which may be cancerous (malignant). In most cases, the tumors arise within the pancreas and/or the upper region of the small intestine (duodenum). Due to excessive acid production (gastric acid hypersecretion), individuals with ZES may develop peptic ulcers of the stomach, the duodenum, and/or other regions of the digestive tract. Peptic ulcers are sores or raw areas within the digestive tract where the lining has been eroded by stomach acid and digestive juices. Symptoms and findings associated with ZES may include mild to severe abdominal pain; diarrhea; gastroinestinal bleeding; increased amounts of fat in the stools (steatorrhea); and/or other abnormalities. Individuals with Zollinger-Ellison syndrome may have giant gastric folds. (For more information on this disorder, choose “Zollinger-Ellison” as your search term in the Rare Disease Database.)Lymphocytic gastritis is a rare disorder characterized by inflammation of the stomach due to the accumulation of inflammatory cells in the inner wall (mucosa) of the stomach resulting in abnormally large, coiled ridges or folds that resemble polyps in the inner wall of the stomach (large gastric folds). Many individuals with lymphocytic gastritis do not have symptoms (asymptomatic). Symptoms that may occur include nausea, vomiting, abdominal pain, diarrhea, and weight loss. The exact cause of lymphocytic gastritis is unknown although the disorder has been linked to celiac sprue and also to Helicobacter pylori infection. (For more information on this disorder, choose “lymphocytic gastritis” as your search term in the Rare Disease Database.)Additional causes of large gastric folds include Helicobacter pylori-associated gastritis, certain infections including syphilis, and various forms of cancer include certain forms of carcinoma or lymphoma. Other rare disorders such as sarcoidosis or Cronkite-Canada disease may also be associated with large gastric folds. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Diagnosis of Menetrier Disease
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Menetrier disease may be suspected in individuals with large gastric folds. Large gastric folds may be diagnosed by a radiologic study after the patient drinks a barium solution or by an endoscopic exam, a procedure in which a thin, flexible tube (endoscope) is inserted through the mouth and used to examine the interior of the stomach and, if necessary, to obtain tissue samples for microscopic study (biopsy). Histopathologic study of affected stomach tissue obtained by biopsy can support a diagnosis of Menetrier disease. Histopathology is the study of microscopic anatomical changes in diseased tissue.
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Diagnosis of Menetrier Disease. Menetrier disease may be suspected in individuals with large gastric folds. Large gastric folds may be diagnosed by a radiologic study after the patient drinks a barium solution or by an endoscopic exam, a procedure in which a thin, flexible tube (endoscope) is inserted through the mouth and used to examine the interior of the stomach and, if necessary, to obtain tissue samples for microscopic study (biopsy). Histopathologic study of affected stomach tissue obtained by biopsy can support a diagnosis of Menetrier disease. Histopathology is the study of microscopic anatomical changes in diseased tissue.
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Therapies of Menetrier Disease
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Treatment
Menetrier disease has been treated with anticholergic drugs, acid suppression therapy, and antibiotic therapy directed against H. pylori infection. These therapies have produced inconsistent results. In some cases, a high-protein diet may be recommended to combat protein loss. Albumin transfusions may also be used to replace albumin loss.Cetuximab (Erbitux) infusions block the epidermal growth factor receptor and have been successful in some patients with Menetrier disease. Cetuximab treatment can improve quality of life, restore gastric acid production and possibly even reduce the thickness of the stomach wall. In a few cases, after cetuximab infusions are discontinued the patient remains well, at least termporarily. Erbitux may cause cardiopulmary arrest, an acne-like rash and low levels of magnesium, and thus patients must be carefully monitored on this treatment. In severe cases such as those with significant protein loss or a high probability of progression to gastric cancer, partial or total gastrectomy may be necessary. Gastrectomy is the surgical removal of part or all of the stomach.In children with Menetrier disease linked to cytomegalovirus infection, antiviral medication directed against cytomegalovirus may lead to improvement of symptoms.Other treatment is symptomatic and supportive.
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Therapies of Menetrier Disease. Treatment
Menetrier disease has been treated with anticholergic drugs, acid suppression therapy, and antibiotic therapy directed against H. pylori infection. These therapies have produced inconsistent results. In some cases, a high-protein diet may be recommended to combat protein loss. Albumin transfusions may also be used to replace albumin loss.Cetuximab (Erbitux) infusions block the epidermal growth factor receptor and have been successful in some patients with Menetrier disease. Cetuximab treatment can improve quality of life, restore gastric acid production and possibly even reduce the thickness of the stomach wall. In a few cases, after cetuximab infusions are discontinued the patient remains well, at least termporarily. Erbitux may cause cardiopulmary arrest, an acne-like rash and low levels of magnesium, and thus patients must be carefully monitored on this treatment. In severe cases such as those with significant protein loss or a high probability of progression to gastric cancer, partial or total gastrectomy may be necessary. Gastrectomy is the surgical removal of part or all of the stomach.In children with Menetrier disease linked to cytomegalovirus infection, antiviral medication directed against cytomegalovirus may lead to improvement of symptoms.Other treatment is symptomatic and supportive.
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Overview of Meningioma
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Summary
A meningioma is a tumor arising from the meninges, which are membranes covering the brain and spinal cord. Excluding brain metastases from other organs, they are the most common intracranial tumor and are the most common primary brain tumor. They arise more commonly in women and in older individuals and develop in around 8 per 100,000 people each year. Compression of the brain and/or spinal cord by a meningioma can lead to symptoms such as headaches, seizures, vision loss, mental changes and weakness. They are mostly treated by surgical removal (resection), which might be combined with radiotherapy, especially if the location of the tumor is such that it is not entirely resectable. Radiation therapy alone can sometimes be used to treat small tumors.IntroductionThe term “meningioma” was coined by Dr. Harvey Cushing in 1922. Since that time, the understanding of meningioma has greatly improved and several subtypes have been identified. As of 2021, the World Health Organization (WHO) classification system changed to use of Arabic numbers for grading and specifying Central Nervous System (CNS) tumors as the 2021 version of WHO classification and recognizing meningioma as a single tumor type with 15 subtypes (ref). Meningiomas remain largely divided into three grades determined by histologic appearance. of The exception remains that grade 1 meningioma will be classified as grade 2 if brain invasion by the tumor is present. Most meningioma (80-85%) are benign tumors (grade 1), 15 to 18% are atypical (grade 2) and 1 to 3% are malignant (grade 3). High grade tumors can arise on their own (de novo) or result from the malignant progression of lower grade tumors.
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Overview of Meningioma. Summary
A meningioma is a tumor arising from the meninges, which are membranes covering the brain and spinal cord. Excluding brain metastases from other organs, they are the most common intracranial tumor and are the most common primary brain tumor. They arise more commonly in women and in older individuals and develop in around 8 per 100,000 people each year. Compression of the brain and/or spinal cord by a meningioma can lead to symptoms such as headaches, seizures, vision loss, mental changes and weakness. They are mostly treated by surgical removal (resection), which might be combined with radiotherapy, especially if the location of the tumor is such that it is not entirely resectable. Radiation therapy alone can sometimes be used to treat small tumors.IntroductionThe term “meningioma” was coined by Dr. Harvey Cushing in 1922. Since that time, the understanding of meningioma has greatly improved and several subtypes have been identified. As of 2021, the World Health Organization (WHO) classification system changed to use of Arabic numbers for grading and specifying Central Nervous System (CNS) tumors as the 2021 version of WHO classification and recognizing meningioma as a single tumor type with 15 subtypes (ref). Meningiomas remain largely divided into three grades determined by histologic appearance. of The exception remains that grade 1 meningioma will be classified as grade 2 if brain invasion by the tumor is present. Most meningioma (80-85%) are benign tumors (grade 1), 15 to 18% are atypical (grade 2) and 1 to 3% are malignant (grade 3). High grade tumors can arise on their own (de novo) or result from the malignant progression of lower grade tumors.
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Symptoms of Meningioma
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Meningioma can occur at any age but tend to occur in older individuals; the median age at diagnosis is 65 years (meaning that half of diagnosed people will be over that age and the other half below). The potential symptoms of meningioma are variable and depend on the location of the tumor and the locations of the brain and spine that are compromised.Parasagittal meningioma can lead to symptoms such as headaches, seizures, and limb weakness. Pressure inside the skull (intracranial pressure) might be increased and lead to swelling of the optic nerve (papilledema) and blurry vision. Other visual defects can also develop. Compression on the frontal lobe can lead to personality changes, decreased cognition, and lack of emotion and interest (apathy). Involvement of the cerebellum can lead to gait imbalance (ataxia), decreased coordination (dysmetria), and involuntary eye movements (nystagmus). Hearing loss can occur if the tumor is located at the junction between the cerebellum and a region of the brainstem known as the pons (cerebellopontine angle). A tumor located in the opening of the skull where the spinal cord connects with the brainstem (foramen magnum) can also lead to arm and leg weakness. Compression from a meningioma can also impair cerebrospinal fluid drainage and lead to accumulation of cerebrospinal fluid in the brain, a condition known as hydrocephalus (for more information on this disorder, choose “hydrocephalus” as your search term in the Rare Disease Database). About 10% of meningioma occur in the spine (spinal meningioma), most commonly in the thoracic portion. Symptoms associated with spinal cord lesions include difficulty walking, leg weakness and numbness, pain, and difficulty with urination and/or bowel movements.As most meningioma are benign, survival rates of affected individuals are relatively high: more than 80% of patients survive more than 5 years, around 75% survive more than 10 years, and about 70% survive more than 15 years. Older age, male gender, poor baseline health and high grade tumors are associated with lower survival rates.Lower grade meningioma that are completely removed surgically do not usually recur. However, some tumors cannot be removed completely due to their location and proximity to crucial structures. A rule of thumb for recurrence of an incompletely resected meningioma is that the rate of recurrence is 30, 60 and 90% at 5, 10 and 15 years, respectively. Higher grade tumors might recur even with apparent complete resection, most often within 2 or 3 years. Tumors that have already recurred have a higher chance of recurring again, usually within a shorter time interval. Metastases to the spine and other organs are rare in meningioma and are most commonly associated with grade 3 tumors.
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Symptoms of Meningioma. Meningioma can occur at any age but tend to occur in older individuals; the median age at diagnosis is 65 years (meaning that half of diagnosed people will be over that age and the other half below). The potential symptoms of meningioma are variable and depend on the location of the tumor and the locations of the brain and spine that are compromised.Parasagittal meningioma can lead to symptoms such as headaches, seizures, and limb weakness. Pressure inside the skull (intracranial pressure) might be increased and lead to swelling of the optic nerve (papilledema) and blurry vision. Other visual defects can also develop. Compression on the frontal lobe can lead to personality changes, decreased cognition, and lack of emotion and interest (apathy). Involvement of the cerebellum can lead to gait imbalance (ataxia), decreased coordination (dysmetria), and involuntary eye movements (nystagmus). Hearing loss can occur if the tumor is located at the junction between the cerebellum and a region of the brainstem known as the pons (cerebellopontine angle). A tumor located in the opening of the skull where the spinal cord connects with the brainstem (foramen magnum) can also lead to arm and leg weakness. Compression from a meningioma can also impair cerebrospinal fluid drainage and lead to accumulation of cerebrospinal fluid in the brain, a condition known as hydrocephalus (for more information on this disorder, choose “hydrocephalus” as your search term in the Rare Disease Database). About 10% of meningioma occur in the spine (spinal meningioma), most commonly in the thoracic portion. Symptoms associated with spinal cord lesions include difficulty walking, leg weakness and numbness, pain, and difficulty with urination and/or bowel movements.As most meningioma are benign, survival rates of affected individuals are relatively high: more than 80% of patients survive more than 5 years, around 75% survive more than 10 years, and about 70% survive more than 15 years. Older age, male gender, poor baseline health and high grade tumors are associated with lower survival rates.Lower grade meningioma that are completely removed surgically do not usually recur. However, some tumors cannot be removed completely due to their location and proximity to crucial structures. A rule of thumb for recurrence of an incompletely resected meningioma is that the rate of recurrence is 30, 60 and 90% at 5, 10 and 15 years, respectively. Higher grade tumors might recur even with apparent complete resection, most often within 2 or 3 years. Tumors that have already recurred have a higher chance of recurring again, usually within a shorter time interval. Metastases to the spine and other organs are rare in meningioma and are most commonly associated with grade 3 tumors.
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Causes of Meningioma
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As their name indicates, meningioma is derived from the meninges, which are membranes that cover the brain and spinal cords. More specifically, most meningioma originate from a type of cells within the meninges known as arachnoid cap cells, which are involved in the resorption of cerebrospinal fluid.Although the exact reasons why meningioma occur in certain individuals is unknown in most cases, several molecular mechanisms are thought to be involved in the development of meningioma. Several genes are often changed (mutated) in meningioma cells, one of the most important being NF2. This gene produces merlin, a tumor suppressor protein that decreases (inhibits) the growth of cells that are in contact with each other. Meningioma cells have also been shown to express the survivin protein, which is an inhibitor of programmed cell death (apoptosis). Growth factors and growth factor receptors such as platelet-derived growth factor and HER2 also play a role in the development of some meningioma. Tumors overexpressing HER2 seem to be associated with a higher recurrence rate.Meningioma shares other features that are characteristic of many types of tumors: they tend to generate numerous blood vessels that will allow an increased influx of nutrients that can facilitate growth. Vascular endothelial growth factor (VEGF) is involved in the development of new blood vessels (angiogenesis) and is frequently overexpressed by numerous tumors including meningioma. A feature more common in malignant meningioma is an increased ability to elongate telomeres due to mutations in the TERT gene. Telomeres are located at the end of chromosome and shorten with each cell division until they become too short for the cell to divide. They can be elongated by the enzyme telomerase, therefore giving an increased replication potential to cells and facilitating tumor growth. The TERT gene encodes a subunit of the telomerase enzyme.Another recently identified poor prognosis genetic mutation is the homozygous loss of CDKN2A [Sievers 2020]. Patients with meningiomas harboring this homozygous deletion had a far short time to recurrence that those who did not. Several meningioma harbor progesterone, estrogen, and androgen receptors, which indicates that hormones might potentially be involved in the growth of some meningioma. Other factors suggesting a role of sex hormones in meningioma is the fact that they are more common in women and that associated symptoms can increase during periods of progesterone excess, such as pregnancy. The role of sex hormones in the development and growth of meningioma is however not entirely understood.
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Causes of Meningioma. As their name indicates, meningioma is derived from the meninges, which are membranes that cover the brain and spinal cords. More specifically, most meningioma originate from a type of cells within the meninges known as arachnoid cap cells, which are involved in the resorption of cerebrospinal fluid.Although the exact reasons why meningioma occur in certain individuals is unknown in most cases, several molecular mechanisms are thought to be involved in the development of meningioma. Several genes are often changed (mutated) in meningioma cells, one of the most important being NF2. This gene produces merlin, a tumor suppressor protein that decreases (inhibits) the growth of cells that are in contact with each other. Meningioma cells have also been shown to express the survivin protein, which is an inhibitor of programmed cell death (apoptosis). Growth factors and growth factor receptors such as platelet-derived growth factor and HER2 also play a role in the development of some meningioma. Tumors overexpressing HER2 seem to be associated with a higher recurrence rate.Meningioma shares other features that are characteristic of many types of tumors: they tend to generate numerous blood vessels that will allow an increased influx of nutrients that can facilitate growth. Vascular endothelial growth factor (VEGF) is involved in the development of new blood vessels (angiogenesis) and is frequently overexpressed by numerous tumors including meningioma. A feature more common in malignant meningioma is an increased ability to elongate telomeres due to mutations in the TERT gene. Telomeres are located at the end of chromosome and shorten with each cell division until they become too short for the cell to divide. They can be elongated by the enzyme telomerase, therefore giving an increased replication potential to cells and facilitating tumor growth. The TERT gene encodes a subunit of the telomerase enzyme.Another recently identified poor prognosis genetic mutation is the homozygous loss of CDKN2A [Sievers 2020]. Patients with meningiomas harboring this homozygous deletion had a far short time to recurrence that those who did not. Several meningioma harbor progesterone, estrogen, and androgen receptors, which indicates that hormones might potentially be involved in the growth of some meningioma. Other factors suggesting a role of sex hormones in meningioma is the fact that they are more common in women and that associated symptoms can increase during periods of progesterone excess, such as pregnancy. The role of sex hormones in the development and growth of meningioma is however not entirely understood.
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Affects of Meningioma
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In the United States, about 40% of primary brain tumors are meningiomas. In 2023, it is estimated that about 42,000 people will be diagnosed with meningioma. However, this is likely an underestimation, as autopsy data shows that up to 2.8% of individuals have a meningioma. Most of these tumors are too small to cause symptoms and will never grow enough to be clinically significant.Meningioma most commonly occur in older individuals, the median age at diagnosis being 65 (meaning that half of diagnosed people will be over that age and the other half below). They rarely occur in children. Notably, they arise in association with syndromes such as neurofibromatosis type II (see the “related disorders” section for more details). They occur 2 to 3 times more commonly in adult women, but are equally common in boys and girls and in the case of malignant meningioma. Spinal meningioma occurs at a 9:1 female: male ratio. Meningioma is also slightly more common in black individuals. Another well-established risk factor is previous exposure to ionizing radiation, such as in the case of individuals who have previously been treated with radiotherapy to the head. Radiation-associated meningioma are more likely to be atypical or malignant and multiple. More often, they occur 15 or more years after exposure to radiation.
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Affects of Meningioma. In the United States, about 40% of primary brain tumors are meningiomas. In 2023, it is estimated that about 42,000 people will be diagnosed with meningioma. However, this is likely an underestimation, as autopsy data shows that up to 2.8% of individuals have a meningioma. Most of these tumors are too small to cause symptoms and will never grow enough to be clinically significant.Meningioma most commonly occur in older individuals, the median age at diagnosis being 65 (meaning that half of diagnosed people will be over that age and the other half below). They rarely occur in children. Notably, they arise in association with syndromes such as neurofibromatosis type II (see the “related disorders” section for more details). They occur 2 to 3 times more commonly in adult women, but are equally common in boys and girls and in the case of malignant meningioma. Spinal meningioma occurs at a 9:1 female: male ratio. Meningioma is also slightly more common in black individuals. Another well-established risk factor is previous exposure to ionizing radiation, such as in the case of individuals who have previously been treated with radiotherapy to the head. Radiation-associated meningioma are more likely to be atypical or malignant and multiple. More often, they occur 15 or more years after exposure to radiation.
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Related disorders of Meningioma
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Disorders related to meningioma can be divided in two categories: syndromes with several symptoms and features, one of which is an increased risk of meningioma, and diseases that are not meningioma, but where affected individuals can have similar symptoms to individuals with meningioma.Syndromes associated with the development of meningiomaNeurofibromatosis 2 (NF2) is a rare genetic disorder that is primarily characterized by benign tumors derived from Schwann cells (schwannoma), which are cells that form the insulating myelin sheath around nerves outside of the brain and spinal cord (peripheral nervous system). In NF2, schwannoma typically form around both vestibulocochlear nerves, which transmits balance and sound impulses from the inner ears to the brain. These tumors are called vestibular schwannomas or acoustic neuromas. Individuals with NF2 are also at increased risk of developing cataracts and certain tumors of the brain and spinal cord, including meningiomas. (For more information on this disorder, choose “neurofibromatosis 2” as your search term in the Rare Disease Database.)
Schwannomatosis is a disorder characterized by the presence of multiple schwannomas, nearly always without the vestibular schwannomas that are diagnostic of NF2. Patients with schwannomatosis may develop benign tumors in the brain (including meningioma) and along the spinal or peripheral nerves.Meningioma also occurs at higher rates in individuals with cancer predisposition syndromes. These syndromes are multiple and include Gorlin syndrome, Cowden syndrome, Li-Fraumeni syndrome, and Von Hippel-Lindau syndrome. (For more information on these disorders, choose the specific disease name as your search term in the Rare Disease Database.)Diseases with symptoms similar to those of meningiomaOther types of brain tumors have symptoms similar to meningioma. They are classified according to their origin. Examples include gliomas, medulloblastomas, and brain metastases, which are more common than tumors arising in the brain (primary brain tumors) and come from cancers elsewhere in the body, including the lungs, breasts, and gastrointestinal tract (For more information on glioma or medulloblastoma, choose the name of the tumor as your search term in the Rare Disease Database.)Intracranial abscesses can also lead to neurological symptoms similar to those present in a meningioma. Causes of brain abscesses are multiple and include bacterial meningitis, fungal and parasitic infections (cryptococcosis and cysticercosis, respectively), infection of a blood clot in the brain (septic cerebral embolus), and inflammation of the brain (encephalitis).
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Related disorders of Meningioma. Disorders related to meningioma can be divided in two categories: syndromes with several symptoms and features, one of which is an increased risk of meningioma, and diseases that are not meningioma, but where affected individuals can have similar symptoms to individuals with meningioma.Syndromes associated with the development of meningiomaNeurofibromatosis 2 (NF2) is a rare genetic disorder that is primarily characterized by benign tumors derived from Schwann cells (schwannoma), which are cells that form the insulating myelin sheath around nerves outside of the brain and spinal cord (peripheral nervous system). In NF2, schwannoma typically form around both vestibulocochlear nerves, which transmits balance and sound impulses from the inner ears to the brain. These tumors are called vestibular schwannomas or acoustic neuromas. Individuals with NF2 are also at increased risk of developing cataracts and certain tumors of the brain and spinal cord, including meningiomas. (For more information on this disorder, choose “neurofibromatosis 2” as your search term in the Rare Disease Database.)
Schwannomatosis is a disorder characterized by the presence of multiple schwannomas, nearly always without the vestibular schwannomas that are diagnostic of NF2. Patients with schwannomatosis may develop benign tumors in the brain (including meningioma) and along the spinal or peripheral nerves.Meningioma also occurs at higher rates in individuals with cancer predisposition syndromes. These syndromes are multiple and include Gorlin syndrome, Cowden syndrome, Li-Fraumeni syndrome, and Von Hippel-Lindau syndrome. (For more information on these disorders, choose the specific disease name as your search term in the Rare Disease Database.)Diseases with symptoms similar to those of meningiomaOther types of brain tumors have symptoms similar to meningioma. They are classified according to their origin. Examples include gliomas, medulloblastomas, and brain metastases, which are more common than tumors arising in the brain (primary brain tumors) and come from cancers elsewhere in the body, including the lungs, breasts, and gastrointestinal tract (For more information on glioma or medulloblastoma, choose the name of the tumor as your search term in the Rare Disease Database.)Intracranial abscesses can also lead to neurological symptoms similar to those present in a meningioma. Causes of brain abscesses are multiple and include bacterial meningitis, fungal and parasitic infections (cryptococcosis and cysticercosis, respectively), infection of a blood clot in the brain (septic cerebral embolus), and inflammation of the brain (encephalitis).
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Meningioma
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Diagnosis of Meningioma
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The diagnosis of meningioma is mostly based on a patient history and physical examination, medical imaging, and analysis of the cells composing the tumor. A patient that has signs and symptoms suggestive of a central nervous system lesion such as recent onset of seizures or neurological deficits (for more details, see the “Signs & Symptoms” section) will usually undergo brain and/or spine medical imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI). MRI is the imaging modality of choice for initial evaluation of brain tumors. Although the presence of a meningioma can be suspected with medical imaging due to their characteristic location, analysis of the cells of the tumor provides the most definitive diagnosis. Meningioma cells can be obtained by removing a piece of the tumor with a biopsy. However, meningiomas are usually removed surgically without a prior biopsy as this provides therapeutic in addition to diagnostic benefit. Once tumor cells are obtained, they can be analyzed under the microscope by a pathologist, who will confirm the diagnosis. A laboratory technique called immunohistochemistry can be used to stain meningioma cells to facilitate their identification.
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Diagnosis of Meningioma. The diagnosis of meningioma is mostly based on a patient history and physical examination, medical imaging, and analysis of the cells composing the tumor. A patient that has signs and symptoms suggestive of a central nervous system lesion such as recent onset of seizures or neurological deficits (for more details, see the “Signs & Symptoms” section) will usually undergo brain and/or spine medical imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI). MRI is the imaging modality of choice for initial evaluation of brain tumors. Although the presence of a meningioma can be suspected with medical imaging due to their characteristic location, analysis of the cells of the tumor provides the most definitive diagnosis. Meningioma cells can be obtained by removing a piece of the tumor with a biopsy. However, meningiomas are usually removed surgically without a prior biopsy as this provides therapeutic in addition to diagnostic benefit. Once tumor cells are obtained, they can be analyzed under the microscope by a pathologist, who will confirm the diagnosis. A laboratory technique called immunohistochemistry can be used to stain meningioma cells to facilitate their identification.
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Meningioma
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Therapies of Meningioma
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Treatment & Management
The standard treatment for meningioma is complete removal (resection) of the tumor. This procedure is performed by a neurosurgeon; a physician specialized in the surgical treatment of diseases of the nervous system. To access the brain to resect the tumor, a part of the skull is removed (craniotomy) and put back in place after the surgery. If the tumor has a high blood supply that might complicate surgery, a technique called angiography might be used before surgery to block (embolize) the blood vessels that feed the tumor to facilitate its resection. Different surgical techniques can be used in the case of spinal meningiomas. Often, surgery alone will be sufficient. However, if the location of the tumor is such that it cannot be entirely resected due to proximity to crucial structures, radiation therapy can be used alone or in combination with surgery. Radiation oncologists are physicians specialized in the use of radiation therapy for the treatment of tumors and cancers. Radiation therapy involves the use of high-energy x-rays or other types or energy to destroy tumor cells. For meningioma, external-beam radiation therapy is most commonly used. Many types of machines can be used for external-beam radiation therapy, but the goal is the same in all cases: to target the tumor and expose it to multiple beams of radiation to stop it from growing while avoiding damage to healthy brain tissue as much as possible. Due to the high risk of recurrence, radiation therapy is often used intentionally after surgery in the case of many atypical meningiomas and routinely with all malignant meningioma, even if the tumor has been completely resected. Radiation therapy might be used alone if the tumor is not accessible by surgery. Chemotherapy and other drugs are not routinely used for the treatment of meningioma. With regards to supportive medications to treat side effects of meningiomas, anti-seizure medication (anticonvulsants) are often used if the affected individual experiences seizures. After treatment, patients might have to undergo rehabilitation to recover functions affected by the tumor or its treatment. Rehabilitation teams comprise many health professionals, including physicians, physiotherapists, occupational therapists, and nurses.
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Therapies of Meningioma. Treatment & Management
The standard treatment for meningioma is complete removal (resection) of the tumor. This procedure is performed by a neurosurgeon; a physician specialized in the surgical treatment of diseases of the nervous system. To access the brain to resect the tumor, a part of the skull is removed (craniotomy) and put back in place after the surgery. If the tumor has a high blood supply that might complicate surgery, a technique called angiography might be used before surgery to block (embolize) the blood vessels that feed the tumor to facilitate its resection. Different surgical techniques can be used in the case of spinal meningiomas. Often, surgery alone will be sufficient. However, if the location of the tumor is such that it cannot be entirely resected due to proximity to crucial structures, radiation therapy can be used alone or in combination with surgery. Radiation oncologists are physicians specialized in the use of radiation therapy for the treatment of tumors and cancers. Radiation therapy involves the use of high-energy x-rays or other types or energy to destroy tumor cells. For meningioma, external-beam radiation therapy is most commonly used. Many types of machines can be used for external-beam radiation therapy, but the goal is the same in all cases: to target the tumor and expose it to multiple beams of radiation to stop it from growing while avoiding damage to healthy brain tissue as much as possible. Due to the high risk of recurrence, radiation therapy is often used intentionally after surgery in the case of many atypical meningiomas and routinely with all malignant meningioma, even if the tumor has been completely resected. Radiation therapy might be used alone if the tumor is not accessible by surgery. Chemotherapy and other drugs are not routinely used for the treatment of meningioma. With regards to supportive medications to treat side effects of meningiomas, anti-seizure medication (anticonvulsants) are often used if the affected individual experiences seizures. After treatment, patients might have to undergo rehabilitation to recover functions affected by the tumor or its treatment. Rehabilitation teams comprise many health professionals, including physicians, physiotherapists, occupational therapists, and nurses.
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Meningioma
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Overview of Meningitis
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Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. The disorder can occur in three different forms: adult, infantile, and neonatal. This inflammation may be caused by different types of bacteria, viruses, fungi, or malignant tumors. Chemical reactions to certain injections into the spinal canal can also cause Meningitis. This inflammation can begin suddenly (acute) or develop gradually (subacute). Adult forms of Meningitis are characterized by fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may occur. Treatment with antibiotics is usually effective against the infection.
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Overview of Meningitis. Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. The disorder can occur in three different forms: adult, infantile, and neonatal. This inflammation may be caused by different types of bacteria, viruses, fungi, or malignant tumors. Chemical reactions to certain injections into the spinal canal can also cause Meningitis. This inflammation can begin suddenly (acute) or develop gradually (subacute). Adult forms of Meningitis are characterized by fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may occur. Treatment with antibiotics is usually effective against the infection.
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Meningitis
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Symptoms of Meningitis
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Meningitis in adults and children is often preceded by respiratory illness or a sore throat. In its acute form, the disorder is characterized by fever, headache, a stiff neck, and vomiting. Adults may become seriously ill within 24 hours. In children, the course of the infection may be even shorter. Symptoms among older children and adults may progress from irritability through confusion, drowsiness, and stupor, possibly leading to coma. Dehydration often occurs, and collapse of the blood vessels may lead to shock (Waterhouse-Friderichsen Syndrome), especially when the Meningitis is caused by meningococcus bacteria which spreads to the blood (septicemia). Paralysis of one side of the body (hemiparesis) is uncommon early in the course of Meningitis, but may occur later as a result of tissue death in the brain (cerebral infarction). Meningitis may recur even after treatment with antibiotics.Infantile Meningitis: The course of the disorder is less predictable among infants between 3 months and 2 years of age. Fever, vomiting, irritability, and convulsions usually occur. A high-pitched cry, and a bulging or tight soft spot (fontanel) on the crown of the head (where the parts of the still unhardened bones join) may also occur. Since the incidence of Meningitis is highest among this age group, any unexplained fever needs to be closely watched. Cerebral fluid may accumulate just inside the tough outer membrane covering the brain (subdural effusions) after several days. Typical signs of Meningitis include seizures, a persistent fever, and an enlarging head size. A brain abscess or subdural pus accumulation may also occur. Water accumulating in the brain (hydrocephalus), deafness and slowed mental and physical development are possible effects of Meningitis on the central nervous system.Neonatal Meningitis: Meningitis in newborn babies can begin during the first 4 weeks of life. It may be caused by infections in parts of the body other than the brain or spine. Some cases may arise from complications occurring at birth. The disorder is characterized by subtle and non-specific signs such as jitteriness, interrupted breathing (apnea), vomiting, diarrhea, and a yellowish skin color (jaundice). Usually signs of infection elsewhere in the body (e.g. middle ear infection) are also present. The cerebrospinal fluid can be tested for a definite diagnosis.Meningitis due to Group B pneumococcus bacteria may be present in the first 10 days of life, when it frequently accompanies a lung illness. Usually, however, this form of Meningitis occurs after 10 days of age as an isolated illness. Neonatal Meningitis is also characterized by symptoms such as fever, drowsiness, and seizures.
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Symptoms of Meningitis. Meningitis in adults and children is often preceded by respiratory illness or a sore throat. In its acute form, the disorder is characterized by fever, headache, a stiff neck, and vomiting. Adults may become seriously ill within 24 hours. In children, the course of the infection may be even shorter. Symptoms among older children and adults may progress from irritability through confusion, drowsiness, and stupor, possibly leading to coma. Dehydration often occurs, and collapse of the blood vessels may lead to shock (Waterhouse-Friderichsen Syndrome), especially when the Meningitis is caused by meningococcus bacteria which spreads to the blood (septicemia). Paralysis of one side of the body (hemiparesis) is uncommon early in the course of Meningitis, but may occur later as a result of tissue death in the brain (cerebral infarction). Meningitis may recur even after treatment with antibiotics.Infantile Meningitis: The course of the disorder is less predictable among infants between 3 months and 2 years of age. Fever, vomiting, irritability, and convulsions usually occur. A high-pitched cry, and a bulging or tight soft spot (fontanel) on the crown of the head (where the parts of the still unhardened bones join) may also occur. Since the incidence of Meningitis is highest among this age group, any unexplained fever needs to be closely watched. Cerebral fluid may accumulate just inside the tough outer membrane covering the brain (subdural effusions) after several days. Typical signs of Meningitis include seizures, a persistent fever, and an enlarging head size. A brain abscess or subdural pus accumulation may also occur. Water accumulating in the brain (hydrocephalus), deafness and slowed mental and physical development are possible effects of Meningitis on the central nervous system.Neonatal Meningitis: Meningitis in newborn babies can begin during the first 4 weeks of life. It may be caused by infections in parts of the body other than the brain or spine. Some cases may arise from complications occurring at birth. The disorder is characterized by subtle and non-specific signs such as jitteriness, interrupted breathing (apnea), vomiting, diarrhea, and a yellowish skin color (jaundice). Usually signs of infection elsewhere in the body (e.g. middle ear infection) are also present. The cerebrospinal fluid can be tested for a definite diagnosis.Meningitis due to Group B pneumococcus bacteria may be present in the first 10 days of life, when it frequently accompanies a lung illness. Usually, however, this form of Meningitis occurs after 10 days of age as an isolated illness. Neonatal Meningitis is also characterized by symptoms such as fever, drowsiness, and seizures.
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Meningitis
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Causes of Meningitis
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Meningitis can be caused by different bacteria, viruses and organisms such as Neisseria meningitis, Hemophilus influenzae b, Streptococcus (Diplococcus) pneumoniae, Group A Streptococcus, Escherichia coli or other gram-negative organisms (chiefly Pseudomonas), and Staphylococcus aureus.Recurrent Meningitis occurs in special situations: 1) When there is a communication between the brain and the exterior that may be inborn or occur after an injury; 2) When infection occurs in areas close to the meninges as in mastoid infection, sinus infection, brain abscess, accumulation of pus under the outer meninge (subdural empyema), or spinal epidural abscess; 3) When the patient has impaired immunity against bacteria or other causes of illness.
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Causes of Meningitis. Meningitis can be caused by different bacteria, viruses and organisms such as Neisseria meningitis, Hemophilus influenzae b, Streptococcus (Diplococcus) pneumoniae, Group A Streptococcus, Escherichia coli or other gram-negative organisms (chiefly Pseudomonas), and Staphylococcus aureus.Recurrent Meningitis occurs in special situations: 1) When there is a communication between the brain and the exterior that may be inborn or occur after an injury; 2) When infection occurs in areas close to the meninges as in mastoid infection, sinus infection, brain abscess, accumulation of pus under the outer meninge (subdural empyema), or spinal epidural abscess; 3) When the patient has impaired immunity against bacteria or other causes of illness.
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Meningitis
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Affects of Meningitis
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Aproximately 3,000 cases of Meningitis have been reported in 1997. Meningitis caused by Hemophilus influenzae occurs most often in children before the age of five to six years.Neonatal Meningitis usually occurs during the first four weeks of life, and predominantly affects infants of low birth weight who have had complications at birth. This form of the disorder occurs in approximately two out of 10,000 full-term infants, and in two out of 1,000 low birth weight infants. This form of Meningitis predominantly affects males.
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Affects of Meningitis. Aproximately 3,000 cases of Meningitis have been reported in 1997. Meningitis caused by Hemophilus influenzae occurs most often in children before the age of five to six years.Neonatal Meningitis usually occurs during the first four weeks of life, and predominantly affects infants of low birth weight who have had complications at birth. This form of the disorder occurs in approximately two out of 10,000 full-term infants, and in two out of 1,000 low birth weight infants. This form of Meningitis predominantly affects males.
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Meningitis
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Related disorders of Meningitis
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Symptoms of the following disorders may resemble those of Meningitis. Comparisons may be useful for a differential diagnosis:Encephalitis is a brain infection. There are different types of this disorder which are caused by different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by a virus or other protein that is foreign to the body. Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness. This disorder may have some symptoms similar to those of Meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, possible convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)
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Related disorders of Meningitis. Symptoms of the following disorders may resemble those of Meningitis. Comparisons may be useful for a differential diagnosis:Encephalitis is a brain infection. There are different types of this disorder which are caused by different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by a virus or other protein that is foreign to the body. Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness. This disorder may have some symptoms similar to those of Meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, possible convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)
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Meningitis
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Diagnosis of Meningitis
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Diagnosis of Meningitis.
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Meningitis
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Therapies of Meningitis
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Meningitis is usually treated with different types of antibiotics used against the specific bacteria causing the infection. These may include ampicillin, chloramphenicol, gentamicin, penicillin, moxalactam, nafcillin, or in tuberculosis cases isoniazid.Children more than two years of age can be immunized against Meningitis with the Haemophilus influenzae type b polysaccharide vaccine.A vaccine composed of attenuated bacteria with added protein, has been approved for use in children under two years of age to protect them against Haemophilus influenzae type B Meningitis.The Food and Drug Administration (FDA) approved Prevnar vaccine for the treatment of meningitis. Because of the high cost of the drug, the FDA limited the potential recipients to children less than two years of age and children from high risk groups (i.e., Native Americans, African Americans, Alaskan Americans, and individuals with HIV, sickle cell anemia, and immunodeficiency disorders.
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Therapies of Meningitis. Meningitis is usually treated with different types of antibiotics used against the specific bacteria causing the infection. These may include ampicillin, chloramphenicol, gentamicin, penicillin, moxalactam, nafcillin, or in tuberculosis cases isoniazid.Children more than two years of age can be immunized against Meningitis with the Haemophilus influenzae type b polysaccharide vaccine.A vaccine composed of attenuated bacteria with added protein, has been approved for use in children under two years of age to protect them against Haemophilus influenzae type B Meningitis.The Food and Drug Administration (FDA) approved Prevnar vaccine for the treatment of meningitis. Because of the high cost of the drug, the FDA limited the potential recipients to children less than two years of age and children from high risk groups (i.e., Native Americans, African Americans, Alaskan Americans, and individuals with HIV, sickle cell anemia, and immunodeficiency disorders.
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Meningitis
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Overview of Meningitis, Bacterial
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Bacterial Meningitis is a central nervous system disease caused by certain types of bacteria. Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. Inflammation can begin suddenly (acute) or develop gradually (subacute). Major symptoms may include fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may occur.
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Overview of Meningitis, Bacterial. Bacterial Meningitis is a central nervous system disease caused by certain types of bacteria. Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. Inflammation can begin suddenly (acute) or develop gradually (subacute). Major symptoms may include fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may occur.
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Meningitis, Bacterial
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Symptoms of Meningitis, Bacterial
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Bacterial Meningitis in adults and children is often preceded by respiratory illness or a sore throat. Most forms of bacterial meningitis are acute. In its acute form, the disorder is characterized by sudden fever, headache, a stiff neck, and vomiting. Adults may become seriously ill within 24 hours. In children, the course of the infection may be even shorter.Symptoms among older children and adults may progress from irritability through confusion, drowsiness, and stupor, possibly leading to coma. Dehydration is common. Other symptoms may include chills, sweating, weakness, loss of appetite, or inability to tolerate bright light (photophobia). Later symptoms may include hydrocephalus (accumulation of fluid in the brain cavity), paralysis of one side of the body (hemiparesis), hearing loss, or other neurological abnormalities.Among infants between 3 months and 2 years of age, fever, refusal of feedings, vomiting, irritability, and convulsions usually occur. A high- pitched cry, and a bulging or tight soft spot (fontanel) on the crown of the head (where the parts of the still unhardened bones join) may also occur. Since the incidence of Meningitis is highest among this age group, any unexplained fever needs to be investigated. Cerebral fluid may accumulate just inside the tough outer membrane covering the brain (subdural effusions) after several days. Typical signs of Meningitis include seizures, a persistent fever, and an enlarging head size. A brain abscess or subdural pus accumulation may also occur. Water accumulating in the brain (hydrocephalus), deafness and slowed mental and physical development are possible effects of Bacterial Meningitis on the central nervous system.A neonatal form of Bacterial Meningitis in newborn babies up to 4 weeks old may be caused by infections in parts of the body other than the brain or spine. Some cases may arise from complications occurring at birth. The disorder is characterized by subtle and nonspecific signs such as jitteriness, interrupted breathing (apnea), vomiting, diarrhea, and a yellowish skin color (jaundice). Usually signs of infection elsewhere in the body (e.g. middle ear infection) are also present. The cerebrospinal fluid can be tested for a definite diagnosis.Bacterial Meningitis due to Group B pneumococcus bacteria may be present in the first 10 days of life, when it frequently accompanies a lung illness. Usually, however, this form of Meningitis occurs after 10 days of age as an isolated illness. Other symptoms such as fever, drowsiness, and seizures may occur.
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Symptoms of Meningitis, Bacterial. Bacterial Meningitis in adults and children is often preceded by respiratory illness or a sore throat. Most forms of bacterial meningitis are acute. In its acute form, the disorder is characterized by sudden fever, headache, a stiff neck, and vomiting. Adults may become seriously ill within 24 hours. In children, the course of the infection may be even shorter.Symptoms among older children and adults may progress from irritability through confusion, drowsiness, and stupor, possibly leading to coma. Dehydration is common. Other symptoms may include chills, sweating, weakness, loss of appetite, or inability to tolerate bright light (photophobia). Later symptoms may include hydrocephalus (accumulation of fluid in the brain cavity), paralysis of one side of the body (hemiparesis), hearing loss, or other neurological abnormalities.Among infants between 3 months and 2 years of age, fever, refusal of feedings, vomiting, irritability, and convulsions usually occur. A high- pitched cry, and a bulging or tight soft spot (fontanel) on the crown of the head (where the parts of the still unhardened bones join) may also occur. Since the incidence of Meningitis is highest among this age group, any unexplained fever needs to be investigated. Cerebral fluid may accumulate just inside the tough outer membrane covering the brain (subdural effusions) after several days. Typical signs of Meningitis include seizures, a persistent fever, and an enlarging head size. A brain abscess or subdural pus accumulation may also occur. Water accumulating in the brain (hydrocephalus), deafness and slowed mental and physical development are possible effects of Bacterial Meningitis on the central nervous system.A neonatal form of Bacterial Meningitis in newborn babies up to 4 weeks old may be caused by infections in parts of the body other than the brain or spine. Some cases may arise from complications occurring at birth. The disorder is characterized by subtle and nonspecific signs such as jitteriness, interrupted breathing (apnea), vomiting, diarrhea, and a yellowish skin color (jaundice). Usually signs of infection elsewhere in the body (e.g. middle ear infection) are also present. The cerebrospinal fluid can be tested for a definite diagnosis.Bacterial Meningitis due to Group B pneumococcus bacteria may be present in the first 10 days of life, when it frequently accompanies a lung illness. Usually, however, this form of Meningitis occurs after 10 days of age as an isolated illness. Other symptoms such as fever, drowsiness, and seizures may occur.
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Meningitis, Bacterial
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Causes of Meningitis, Bacterial
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Bacterial Meningitis is the most common type of meningitis. Three types of bacteria are responsible for 80% of all Bacterial Meningitis. These are: 1) Hemophilus influenzae (type B), 2) Streptococcus pneumoniae (Pneumococcus), and 3) Neisseria meningitidis (Meningococcus). (For more information on Meningococcal Meningitis, choose “meningococcal” as your search term in the Rare Disease Database). All three types occur most often in winter.Gram-negative bacteria such as Escherichia coli, Klebsiella-Entero, or Pseudomonas often cause Bacterial Meningitis in newborn infants. Other types of bacteria that may cause the disorder are Streptococci, Staphylococci (Staphylococcus aureus) or listeria monocytogenes.Bacterial Meningitis due to hemophilus influenza type B bacteria occurs most often in infants over 1 month old and young children. It usually does not occur in adults except in relation to another condition such as head trauma or impaired immunity. Bacterial Meningitis caused by pneumococcus occurs most often in adults, especially those with alcoholism, chronic otitis (inflammation of the ear), sinusitus (inflammation of the mucous membranes lining the sinuses that open into the nose), mastoiditis (infection of the bone located behind the ear), closed head injury, recurrent meningitis, pneumococcal pneumonia, or sickle cell anemia. (For more information choose “meningitis,” or “sickle” as your search terms in the Rare Disease Database).Bacterial Meningitis from gram-negative organisms such as Escherichia coli and Klebsiella-Enterobacter is called Gram-negative Meningitis and frequently occurs after central nervous system trauma or surgery, or from blood poisoning). Newborns or people who have impaired immunity may also become infected.Staphylococcal Meningitis (from Staphylococcus bacteria), another form of Bacterial Meningitis, occurs after blood poisoning (e.g., from endocarditis which is inflammation of the inner lining of the heart), open head trauma, or neurosurgery.Listeria Meningitis is another form of meningitis that occurs in newborns, in patients who have chronic renal (kidney) failure, or adults taking immunosuppressive drugs (e.g. organ transplant patients). (For more information on Listeria, choose “Listeria” as your search term in the Rare Disease Database).Intravenous drug use from unsterilized needles can cause blood poisoning that may lead to Bacterial Meningitis.Of all bacteria causing Bacterial Meningitis, Hemophilus influenza type B is the most common and represents almost half of all Bacterial Meningitis cases. Meningococcal Meningitis represents about 27 per cent, and Pneumococcal Meningitis represents about 11 per cent.Bacteria that cause Bacterial Meningitis are thought to be carried by approimately ten percent of the population in their throats. It is not clear why only a very small percentage of people get this disease.
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Causes of Meningitis, Bacterial. Bacterial Meningitis is the most common type of meningitis. Three types of bacteria are responsible for 80% of all Bacterial Meningitis. These are: 1) Hemophilus influenzae (type B), 2) Streptococcus pneumoniae (Pneumococcus), and 3) Neisseria meningitidis (Meningococcus). (For more information on Meningococcal Meningitis, choose “meningococcal” as your search term in the Rare Disease Database). All three types occur most often in winter.Gram-negative bacteria such as Escherichia coli, Klebsiella-Entero, or Pseudomonas often cause Bacterial Meningitis in newborn infants. Other types of bacteria that may cause the disorder are Streptococci, Staphylococci (Staphylococcus aureus) or listeria monocytogenes.Bacterial Meningitis due to hemophilus influenza type B bacteria occurs most often in infants over 1 month old and young children. It usually does not occur in adults except in relation to another condition such as head trauma or impaired immunity. Bacterial Meningitis caused by pneumococcus occurs most often in adults, especially those with alcoholism, chronic otitis (inflammation of the ear), sinusitus (inflammation of the mucous membranes lining the sinuses that open into the nose), mastoiditis (infection of the bone located behind the ear), closed head injury, recurrent meningitis, pneumococcal pneumonia, or sickle cell anemia. (For more information choose “meningitis,” or “sickle” as your search terms in the Rare Disease Database).Bacterial Meningitis from gram-negative organisms such as Escherichia coli and Klebsiella-Enterobacter is called Gram-negative Meningitis and frequently occurs after central nervous system trauma or surgery, or from blood poisoning). Newborns or people who have impaired immunity may also become infected.Staphylococcal Meningitis (from Staphylococcus bacteria), another form of Bacterial Meningitis, occurs after blood poisoning (e.g., from endocarditis which is inflammation of the inner lining of the heart), open head trauma, or neurosurgery.Listeria Meningitis is another form of meningitis that occurs in newborns, in patients who have chronic renal (kidney) failure, or adults taking immunosuppressive drugs (e.g. organ transplant patients). (For more information on Listeria, choose “Listeria” as your search term in the Rare Disease Database).Intravenous drug use from unsterilized needles can cause blood poisoning that may lead to Bacterial Meningitis.Of all bacteria causing Bacterial Meningitis, Hemophilus influenza type B is the most common and represents almost half of all Bacterial Meningitis cases. Meningococcal Meningitis represents about 27 per cent, and Pneumococcal Meningitis represents about 11 per cent.Bacteria that cause Bacterial Meningitis are thought to be carried by approimately ten percent of the population in their throats. It is not clear why only a very small percentage of people get this disease.
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Meningitis, Bacterial
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Affects of Meningitis, Bacterial
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In the United States, approximately 2,600 sporadic cases of Bacterial Meningitis are reported each year. Meningitis caused by pneumococcal infections affects about 1.1 in 100,000 individuals. Meningitis caused by haemophilus influenza affects about .2 in 100,000 individuals. About 70 percent of all Bacterial Meningitis occurs in children aged 5 and under. Children under age 2 are at highest risk for infection, and males are affected more often than females. Bacterial Meningitis in general occurs most often during the first month of a newborn's life and is usually caused by gram-negative bacteria such as Escherichia coli or by group B streptococcus. Bacterial Meningitis caused by Hemophilus influenzae type B occurs most often in infants over 1 month old and young children. However, in the United States, this type of Bacterial Meningitis occurs more often in adults as a result of a vaccine that has led to a decline in the number of affected infants and children. Bacterial Meningitis caused by pneumococcus bacteria occurs most often in adults, but there are an estimated 1,400 cases of pneumococcal meningitis each year among children under age five.
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Affects of Meningitis, Bacterial. In the United States, approximately 2,600 sporadic cases of Bacterial Meningitis are reported each year. Meningitis caused by pneumococcal infections affects about 1.1 in 100,000 individuals. Meningitis caused by haemophilus influenza affects about .2 in 100,000 individuals. About 70 percent of all Bacterial Meningitis occurs in children aged 5 and under. Children under age 2 are at highest risk for infection, and males are affected more often than females. Bacterial Meningitis in general occurs most often during the first month of a newborn's life and is usually caused by gram-negative bacteria such as Escherichia coli or by group B streptococcus. Bacterial Meningitis caused by Hemophilus influenzae type B occurs most often in infants over 1 month old and young children. However, in the United States, this type of Bacterial Meningitis occurs more often in adults as a result of a vaccine that has led to a decline in the number of affected infants and children. Bacterial Meningitis caused by pneumococcus bacteria occurs most often in adults, but there are an estimated 1,400 cases of pneumococcal meningitis each year among children under age five.
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Meningitis, Bacterial
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Related disorders of Meningitis, Bacterial
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Symptoms of the following disorders may resemble those of Meningitis. Comparisons may be useful for a differential diagnosis:Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or chemical reactions to certain injections into the spinal canal. (For more information on other types of Meningitis, choose “meningitis” as your search term in the Rare Disease Database.)Encephalitis is a brain infection. There are different types of this disorder which are caused by different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by a virus or other protein that is foreign to the body. Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness. This disorder may have some symptoms similar to those of Meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, possible convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)Primary amebic meningoencephalitis (PAM) is a brain infection. PAM is characterized by a severe headache, high fever, nausea, vomiting, stiff neck, and, in some cases, hallucinations. Some affected individuals may experience seizures, coma, and other life-threatening complications. PAM affects individuals who have inhaled water from lakes, ponds, rivers, or streams contaminated with the microorganism Naegleria fowleri amoebae. The infection most often occurs in warm areas during the summer months. Cases of PAM have been reported mostly in southern and central United States, southern Australia, New Zealand, Europe, Africa, and Central America. Approximately, 100 to 200 cases have been reported in the United States. The diagnosis of PAM may be suspected based upon a thorough clinical evaluation and detailed patient history. Treatment of PAM consists of intravenous and intrathecal amphotericin B and miconazole plus oral rifampin.
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Related disorders of Meningitis, Bacterial. Symptoms of the following disorders may resemble those of Meningitis. Comparisons may be useful for a differential diagnosis:Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or chemical reactions to certain injections into the spinal canal. (For more information on other types of Meningitis, choose “meningitis” as your search term in the Rare Disease Database.)Encephalitis is a brain infection. There are different types of this disorder which are caused by different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by a virus or other protein that is foreign to the body. Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness. This disorder may have some symptoms similar to those of Meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, possible convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)Primary amebic meningoencephalitis (PAM) is a brain infection. PAM is characterized by a severe headache, high fever, nausea, vomiting, stiff neck, and, in some cases, hallucinations. Some affected individuals may experience seizures, coma, and other life-threatening complications. PAM affects individuals who have inhaled water from lakes, ponds, rivers, or streams contaminated with the microorganism Naegleria fowleri amoebae. The infection most often occurs in warm areas during the summer months. Cases of PAM have been reported mostly in southern and central United States, southern Australia, New Zealand, Europe, Africa, and Central America. Approximately, 100 to 200 cases have been reported in the United States. The diagnosis of PAM may be suspected based upon a thorough clinical evaluation and detailed patient history. Treatment of PAM consists of intravenous and intrathecal amphotericin B and miconazole plus oral rifampin.
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Meningitis, Bacterial
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Diagnosis of Meningitis, Bacterial
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Testing for Bacterial Meningitis may include imaging techniques such as CT scans or MR imaging. Other testing may include examination of the patient's blood and/or skin. Diagnosis is made by examination of the cerebrospinal fluid.
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Diagnosis of Meningitis, Bacterial. Testing for Bacterial Meningitis may include imaging techniques such as CT scans or MR imaging. Other testing may include examination of the patient's blood and/or skin. Diagnosis is made by examination of the cerebrospinal fluid.
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Meningitis, Bacterial
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Therapies of Meningitis, Bacterial
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TreatmentBacterial Meningitis is usually treated with different types of antibiotics used against the specific bacteria causing the infection. These may include ampicillin, chloramphenicol, gentamicin, penicillin, moxalactam, nafcillin, cefuroxime, cefotaxime, ceftizoxime, oxacillin, vancomycin, or rifampin. The addition of dexamethasone to the antibiotic treatment is also being used and is helpful in reducing meningeal inflammation. Research has shown that the use of dexamethasone in children may be beneficial when administered within the first two days of the illness.For children under 5 who have come in close contact with a person having Meningitis caused by Hemophilus influenzae, the drug rifampin may be prescribed as a preventative measure.For children under the age of 2, a vaccine approved in February, 2000, helps protect against invasive pneumococcal diseases, including meningitis. Called the Prevnar Pneumococcal 7-valent Conjugate Vaccine, it is marketed by Wyeth-Ayerst Laboratories and is to be given to infants at two, four, and six months and again between 12 and 15 months of age.Children over 2 years of age can be immunized against Meningitis with the Hemophilus influenzae type b polysaccharide vaccine. A vaccine composed of attenuated bacteria with added protein, has been approved for use in children under two years of age to protect them against Hemophilus influenzae type B Meningitis.The Centers for Disease Control (CDC) in Atlanta, GA, have advised that an outbreak of three or more cases of Bacterial Meningitis in a well-defined geographical area (i.e., school, county) be considered a risk factor for contracting this disease. The CDC advises local officials to define the immediate population that is at risk (i.e., day care center, university) and vaccinate those at risk once the disease occurs at a rate of 10 patients per 100,000.
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Therapies of Meningitis, Bacterial. TreatmentBacterial Meningitis is usually treated with different types of antibiotics used against the specific bacteria causing the infection. These may include ampicillin, chloramphenicol, gentamicin, penicillin, moxalactam, nafcillin, cefuroxime, cefotaxime, ceftizoxime, oxacillin, vancomycin, or rifampin. The addition of dexamethasone to the antibiotic treatment is also being used and is helpful in reducing meningeal inflammation. Research has shown that the use of dexamethasone in children may be beneficial when administered within the first two days of the illness.For children under 5 who have come in close contact with a person having Meningitis caused by Hemophilus influenzae, the drug rifampin may be prescribed as a preventative measure.For children under the age of 2, a vaccine approved in February, 2000, helps protect against invasive pneumococcal diseases, including meningitis. Called the Prevnar Pneumococcal 7-valent Conjugate Vaccine, it is marketed by Wyeth-Ayerst Laboratories and is to be given to infants at two, four, and six months and again between 12 and 15 months of age.Children over 2 years of age can be immunized against Meningitis with the Hemophilus influenzae type b polysaccharide vaccine. A vaccine composed of attenuated bacteria with added protein, has been approved for use in children under two years of age to protect them against Hemophilus influenzae type B Meningitis.The Centers for Disease Control (CDC) in Atlanta, GA, have advised that an outbreak of three or more cases of Bacterial Meningitis in a well-defined geographical area (i.e., school, county) be considered a risk factor for contracting this disease. The CDC advises local officials to define the immediate population that is at risk (i.e., day care center, university) and vaccinate those at risk once the disease occurs at a rate of 10 patients per 100,000.
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Meningitis, Bacterial
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nord_794_0
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Overview of Meningitis, Tuberculous
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Tuberculous Meningitis (TBM) is a form of meningitis characterized by inflammation of the membranes (meninges) around the brain or spinal cord and caused by a specific bacterium known as Mycobacterium tuberculosis. In TBM, the disorder develops gradually. Treatment with antibiotics and other drugs is usually effective against the infection.
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Overview of Meningitis, Tuberculous. Tuberculous Meningitis (TBM) is a form of meningitis characterized by inflammation of the membranes (meninges) around the brain or spinal cord and caused by a specific bacterium known as Mycobacterium tuberculosis. In TBM, the disorder develops gradually. Treatment with antibiotics and other drugs is usually effective against the infection.
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Meningitis, Tuberculous
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Symptoms of Meningitis, Tuberculous
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Tuberculous Meningitis involves the central nervous system. Headaches and behavioral changes may be noticed initially. Fever, headache, a stiff neck, and vomiting may also occur. Symptoms among older children and adults may progress from irritability to confusion, drowsiness, and stupor, possibly leading to coma.Untreated, this disorder can lead to seizures, hydrocephalus (accumulation of fluid in the brain cavity), deafness, mental retardation, paralysis of one side of the body (hemiparesis) and other neurological abnormalities. (For more information on this disorder, choose “hydrocephalus” as your search term in the Rare Disease Database).Diagnosis is made by examination of the cerebrospinal fluid.
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Symptoms of Meningitis, Tuberculous. Tuberculous Meningitis involves the central nervous system. Headaches and behavioral changes may be noticed initially. Fever, headache, a stiff neck, and vomiting may also occur. Symptoms among older children and adults may progress from irritability to confusion, drowsiness, and stupor, possibly leading to coma.Untreated, this disorder can lead to seizures, hydrocephalus (accumulation of fluid in the brain cavity), deafness, mental retardation, paralysis of one side of the body (hemiparesis) and other neurological abnormalities. (For more information on this disorder, choose “hydrocephalus” as your search term in the Rare Disease Database).Diagnosis is made by examination of the cerebrospinal fluid.
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Meningitis, Tuberculous
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Causes of Meningitis, Tuberculous
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Tuberculous Meningitis is a rare complication that occurs in some patients who have or have had tuberculosis (TB), especially miliary tuberculosis. It can also occur in people who have been exposed to the bacteria that causes TB. This form of meningitis is caused by a specific bacteria known as Mycobacterium Tuberculosis. (For more information on tuberculosis, choose “tuberculosis” as your search term in the Rare Disease Database).
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Causes of Meningitis, Tuberculous. Tuberculous Meningitis is a rare complication that occurs in some patients who have or have had tuberculosis (TB), especially miliary tuberculosis. It can also occur in people who have been exposed to the bacteria that causes TB. This form of meningitis is caused by a specific bacteria known as Mycobacterium Tuberculosis. (For more information on tuberculosis, choose “tuberculosis” as your search term in the Rare Disease Database).
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Meningitis, Tuberculous
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nord_794_3
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Affects of Meningitis, Tuberculous
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TBM is usually found in children aged one to five years although it may occur at any age.
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Affects of Meningitis, Tuberculous. TBM is usually found in children aged one to five years although it may occur at any age.
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Meningitis, Tuberculous
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Related disorders of Meningitis, Tuberculous
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Symptoms of the following disorders may resemble those of Tuberculous Meningitis. Comparisons may be useful for a differential diagnosis:In general, Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or reactions to certain injections into the spinal canal. (For more information on other forms of meningitis, choose “meningitis” as your search term in the Rare Disease Database.)Encephalitis is an infection of the brain which is brought on by one of several different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by some other non-viral, foreign protein. Many of the symptoms are similar to those of TBM, such as a stiff neck, altered reflexes, confusion, speech disorders, convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)
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Related disorders of Meningitis, Tuberculous. Symptoms of the following disorders may resemble those of Tuberculous Meningitis. Comparisons may be useful for a differential diagnosis:In general, Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or reactions to certain injections into the spinal canal. (For more information on other forms of meningitis, choose “meningitis” as your search term in the Rare Disease Database.)Encephalitis is an infection of the brain which is brought on by one of several different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by some other non-viral, foreign protein. Many of the symptoms are similar to those of TBM, such as a stiff neck, altered reflexes, confusion, speech disorders, convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)
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Meningitis, Tuberculous
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nord_794_5
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Diagnosis of Meningitis, Tuberculous
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Diagnosis of Meningitis, Tuberculous.
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Meningitis, Tuberculous
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Therapies of Meningitis, Tuberculous
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Meningitis is usually treated with antibiotic drugs used against the bacteria causing the infection. These may include isoniazid, rifampin, streptomycin, and ethambutol. Treatment should last for at least 9 months to one year. Corticosteroid drugs such as prednisone may also be of benefit.
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Therapies of Meningitis, Tuberculous. Meningitis is usually treated with antibiotic drugs used against the bacteria causing the infection. These may include isoniazid, rifampin, streptomycin, and ethambutol. Treatment should last for at least 9 months to one year. Corticosteroid drugs such as prednisone may also be of benefit.
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Meningitis, Tuberculous
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nord_795_0
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Overview of Meningococcal Meningitis
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Meningococcal meningitis is a form of meningitis caused by a specific bacterium known as Neisseria meningitidis. Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation can begin suddenly (acute) or develop gradually (subacute). Symptoms may include fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may also occur. Skin rashes occur in about half of all individuals with meningococcal meningitis.Meningococcal meningitis is still associated with a high mortality rate and persistent neurological defects, particularly among infants and young children. Meningococcal meningitis without antibiotic therapy is uniformly fatal.
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Overview of Meningococcal Meningitis. Meningococcal meningitis is a form of meningitis caused by a specific bacterium known as Neisseria meningitidis. Meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation can begin suddenly (acute) or develop gradually (subacute). Symptoms may include fever, headache, and a stiff neck, sometimes with aching muscles. Nausea, vomiting and other symptoms may also occur. Skin rashes occur in about half of all individuals with meningococcal meningitis.Meningococcal meningitis is still associated with a high mortality rate and persistent neurological defects, particularly among infants and young children. Meningococcal meningitis without antibiotic therapy is uniformly fatal.
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Meningococcal Meningitis
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nord_795_1
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Symptoms of Meningococcal Meningitis
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Meningococcal meningitis is one of the three most common types of bacterial meningitis. The incubation period averages 3-4 days (range 1-10 days), which is the period of communicability. It progresses more rapidly than any other acute form of bacterial meningitis. Meningococcal meningitis involves the central nervous system. In adults and children it is often preceded by respiratory illness or a sore throat. In its acute form, the disorder is characterized by fever, headache, a stiff neck, nausea, vomiting and altered mental state such as confusion or coma. Adults may become seriously ill within hours. In children the course of the infection may be even shorter.Meningococcal meningitis evolves when the bacteria, Neisseria meningitidis (N.meningitidis) progresses from initial adherence to the nasopharyngeal (nose and throat) mucosa to invasion of the deeper mucosal layers (the submucosa). These bacteria rapidly multiply, and can lead to a mild (subclinical) infection. However, in approximately 10-20% of cases, the N.meningitidis enters the bloodstream (meningococcemia). This systemic form of the disease, meningococcemia, usually precedes the development of meningococcal meningitis by 24-48 hours.Meningococcemia is characterized by severe, widespread vascular injury, with evidence of circulatory collapse and disseminated intravascular coagulation (DIC) Skin rashes occur in about half of all individuals with meningococcal meningitis. The rash is petechial (tiny, non-raised, purple-reddish lesions that do not blanch when pressed, and are the result of areas of intravascular bleeding.Swelling or inflammation of the brain (cerebral edema or ventriculitis), or hydrocephalus (accumulation of fluid in the brain cavity) may also occur. Additional symptoms may include chills; sweating; weakness; loss of appetite; muscle pain (myalgia) of the lower back or legs; or inability to tolerate bright light (photophobia). (For more information on hydrocephalus, choose “hydrocephalus” as your search term in the Rare Disease Database).Dehydration often occurs in individuals with meningococcal meningitis. In some cases, collapse of the blood vessels may lead to shock (Waterhouse-Friderichsen syndrome) when the meningococcus bacteria spread to the blood (septicemia). Later symptoms may include paralysis of one side of the body (hemiparesis), hearing loss, or additional neurological abnormalities.The course of meningococcal meningitis is less predictable among infants between three months and two years of age. Fever, refusal of feedings, vomiting, irritability, and convulsions usually occur. A high-pitched cry and a bulging or tight soft spot (fontanel) on the crown of the head (where the parts of the skull's still unhardened bones join) may also occur. Since the incidence of most types of meningitis is highest among this age group, any unexplained fever needs to be closely watched. Cerebral fluid may accumulate just inside the tough outer membrane covering the brain (subdural effusions) after several days. Warning signs may include seizures, a persistent fever, and an enlarging head size. A brain abscess or subdural pus accumulation may also occur. Water accumulating in the brain (hydrocephalus), deafness and slowed mental and physical development are possible consequences of meningitis.
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Symptoms of Meningococcal Meningitis. Meningococcal meningitis is one of the three most common types of bacterial meningitis. The incubation period averages 3-4 days (range 1-10 days), which is the period of communicability. It progresses more rapidly than any other acute form of bacterial meningitis. Meningococcal meningitis involves the central nervous system. In adults and children it is often preceded by respiratory illness or a sore throat. In its acute form, the disorder is characterized by fever, headache, a stiff neck, nausea, vomiting and altered mental state such as confusion or coma. Adults may become seriously ill within hours. In children the course of the infection may be even shorter.Meningococcal meningitis evolves when the bacteria, Neisseria meningitidis (N.meningitidis) progresses from initial adherence to the nasopharyngeal (nose and throat) mucosa to invasion of the deeper mucosal layers (the submucosa). These bacteria rapidly multiply, and can lead to a mild (subclinical) infection. However, in approximately 10-20% of cases, the N.meningitidis enters the bloodstream (meningococcemia). This systemic form of the disease, meningococcemia, usually precedes the development of meningococcal meningitis by 24-48 hours.Meningococcemia is characterized by severe, widespread vascular injury, with evidence of circulatory collapse and disseminated intravascular coagulation (DIC) Skin rashes occur in about half of all individuals with meningococcal meningitis. The rash is petechial (tiny, non-raised, purple-reddish lesions that do not blanch when pressed, and are the result of areas of intravascular bleeding.Swelling or inflammation of the brain (cerebral edema or ventriculitis), or hydrocephalus (accumulation of fluid in the brain cavity) may also occur. Additional symptoms may include chills; sweating; weakness; loss of appetite; muscle pain (myalgia) of the lower back or legs; or inability to tolerate bright light (photophobia). (For more information on hydrocephalus, choose “hydrocephalus” as your search term in the Rare Disease Database).Dehydration often occurs in individuals with meningococcal meningitis. In some cases, collapse of the blood vessels may lead to shock (Waterhouse-Friderichsen syndrome) when the meningococcus bacteria spread to the blood (septicemia). Later symptoms may include paralysis of one side of the body (hemiparesis), hearing loss, or additional neurological abnormalities.The course of meningococcal meningitis is less predictable among infants between three months and two years of age. Fever, refusal of feedings, vomiting, irritability, and convulsions usually occur. A high-pitched cry and a bulging or tight soft spot (fontanel) on the crown of the head (where the parts of the skull's still unhardened bones join) may also occur. Since the incidence of most types of meningitis is highest among this age group, any unexplained fever needs to be closely watched. Cerebral fluid may accumulate just inside the tough outer membrane covering the brain (subdural effusions) after several days. Warning signs may include seizures, a persistent fever, and an enlarging head size. A brain abscess or subdural pus accumulation may also occur. Water accumulating in the brain (hydrocephalus), deafness and slowed mental and physical development are possible consequences of meningitis.
| 795 |
Meningococcal Meningitis
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nord_795_2
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Causes of Meningococcal Meningitis
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Meningococcal meningitis is caused by a bacterium known as Neisseria meningitidis. There are several types, or serogroups, of Neisseria meningitidis. The most common of these serogroups are A, B, C, D, X, Y, 29E, and W135. Serogroups A, B, C, and Y are responsible for most meningococcal diseases.The bacterium is spread by droplets in the air or close contact with an infected person. It collects in the nasopharynx, or post-nasal space, that connects the nasal cavities with the throat. The bacterium is transported to the membranes (meninges) around the brain or spinal cord by the blood. It usually spreads from nearby infected areas such as the nasal sinuses or from the cerebrospinal fluid.
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Causes of Meningococcal Meningitis. Meningococcal meningitis is caused by a bacterium known as Neisseria meningitidis. There are several types, or serogroups, of Neisseria meningitidis. The most common of these serogroups are A, B, C, D, X, Y, 29E, and W135. Serogroups A, B, C, and Y are responsible for most meningococcal diseases.The bacterium is spread by droplets in the air or close contact with an infected person. It collects in the nasopharynx, or post-nasal space, that connects the nasal cavities with the throat. The bacterium is transported to the membranes (meninges) around the brain or spinal cord by the blood. It usually spreads from nearby infected areas such as the nasal sinuses or from the cerebrospinal fluid.
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Meningococcal Meningitis
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nord_795_3
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Affects of Meningococcal Meningitis
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Meningococcal meningitis primarily affects infants, children, and young adults. Males are affected slightly more than females, and account for 55% of all cases, with an incidence of 1.2 cases per 100,000 population, compared to 1 case per 100,000 population among females. Meningococcal meningitis can occur as an epidemic in subgroups such as people in the military services or students in dormitories. Vaccines can help control meningitis epidemics caused by serogroups A, B, C, Y, or W135.The age-specific incidence of meningococcal disease is highest in young children, although the incidence of meningococcal disease in adolescents and college-aged young adults appears to have increased. College students living in dormitories seem to be the population at the most increased risk. This is due to the close proximity of students in college dormitories, which allows for faster spread of infection.
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Affects of Meningococcal Meningitis. Meningococcal meningitis primarily affects infants, children, and young adults. Males are affected slightly more than females, and account for 55% of all cases, with an incidence of 1.2 cases per 100,000 population, compared to 1 case per 100,000 population among females. Meningococcal meningitis can occur as an epidemic in subgroups such as people in the military services or students in dormitories. Vaccines can help control meningitis epidemics caused by serogroups A, B, C, Y, or W135.The age-specific incidence of meningococcal disease is highest in young children, although the incidence of meningococcal disease in adolescents and college-aged young adults appears to have increased. College students living in dormitories seem to be the population at the most increased risk. This is due to the close proximity of students in college dormitories, which allows for faster spread of infection.
| 795 |
Meningococcal Meningitis
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nord_795_4
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Related disorders of Meningococcal Meningitis
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Symptoms of the following disorders may resemble those of meningococcal meningitis. Comparisons may be useful for a differential diagnosis:In general, meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or reactions to certain injections into the spinal canal. (For more information on other types of Meningitis, choose “meningitis” as your search term in the Rare Disease Database.)Encephalitis is a brain infection. There are different types of this disorder that are caused by different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by a virus or proteins foreign to the body. Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness. This disorder may have some symptoms similar to those of meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)Rocky Mountain spotted fever is an acute infectious disorder transmitted to humans through the bite of an infected tick, usually in wooded areas of the midwest, eastern and southeastern United States. Fever and rash are among major symptoms. The rash may not develop in all cases, possibly making diagnosis difficult. Swelling (edema), headaches, chills, weakness, and muscle pains may also occur. Severe headaches, lethargy, confusion, delirium, focal neurological deficits, increased pressure in the skull leading to pressure on and swelling of the optic disk (papilledema), seizures and/or coma may occur in untreated cases as the nervous system is progressively affected. Some individuals may have a stiff neck due to muscle pain (myalgia) or irritation of membranes surrounding the brain and spinal cord tissue (meningismus). (For more information on this disorder, choose “Rocky Mountain Spotted Fever” as your search term in the Rare Disease Database.)
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Related disorders of Meningococcal Meningitis. Symptoms of the following disorders may resemble those of meningococcal meningitis. Comparisons may be useful for a differential diagnosis:In general, meningitis is characterized by inflammation of the membranes (meninges) around the brain or spinal cord. This inflammation may be caused by different types of bacteria, viruses, fungi, malignant tumors, or reactions to certain injections into the spinal canal. (For more information on other types of Meningitis, choose “meningitis” as your search term in the Rare Disease Database.)Encephalitis is a brain infection. There are different types of this disorder that are caused by different types of viruses. Encephalitis may also be caused by hypersensitivity initiated by a virus or proteins foreign to the body. Symptoms may include headache, drowsiness, hyperactivity, and/or general weakness. This disorder may have some symptoms similar to those of meningitis such as a stiff neck, altered reflexes, confusion, speech disorders, convulsions, paralysis and coma. (For more information choose “Encephalitis” as your search term in the Rare Disease Database.)Rocky Mountain spotted fever is an acute infectious disorder transmitted to humans through the bite of an infected tick, usually in wooded areas of the midwest, eastern and southeastern United States. Fever and rash are among major symptoms. The rash may not develop in all cases, possibly making diagnosis difficult. Swelling (edema), headaches, chills, weakness, and muscle pains may also occur. Severe headaches, lethargy, confusion, delirium, focal neurological deficits, increased pressure in the skull leading to pressure on and swelling of the optic disk (papilledema), seizures and/or coma may occur in untreated cases as the nervous system is progressively affected. Some individuals may have a stiff neck due to muscle pain (myalgia) or irritation of membranes surrounding the brain and spinal cord tissue (meningismus). (For more information on this disorder, choose “Rocky Mountain Spotted Fever” as your search term in the Rare Disease Database.)
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Meningococcal Meningitis
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Diagnosis of Meningococcal Meningitis
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Testing for meningococcal meningitis may include imaging techniques such as CT scans or magnetic resonance imaging (MRI). Other testing may include examination of the blood and/or skin. Diagnosis is made by laboratory examination of the cerebrospinal fluid that often reveals the presence of bacterial meningitis.
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Diagnosis of Meningococcal Meningitis. Testing for meningococcal meningitis may include imaging techniques such as CT scans or magnetic resonance imaging (MRI). Other testing may include examination of the blood and/or skin. Diagnosis is made by laboratory examination of the cerebrospinal fluid that often reveals the presence of bacterial meningitis.
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Meningococcal Meningitis
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Therapies of Meningococcal Meningitis
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TreatmentThere are 5 subtypes of N. meningitidis. Currently, (as of June, 2012) licensed vaccines for prevention of illness from 4 of the 5 subtypes exists. The vaccines are called Menveo, Menactra and Nimerix. Vaccines with narrow coverage have been used against serogroup B, and a vaccine with broad coverage is in late stage of development. Public health officials recommend that all college students take the meningococcal meningitis immunization. In particular, those who live in close quarters (dormitories, fraternities, and sororities), who frequent bars or consume alcohol, who smoke or are regularly around smokers are at higher risk and should consider vaccination. Students with certain chronic conditions (eg, have had their spleen removed) should be vaccinated. Students traveling to high-risk areas of the world (eg, sub-Sahara Africa) should consider vaccination. The conjugate vaccine is now also recommended for all children when they reach 11-12 years of age.Meningococcal meningitis is usually treated with antibiotic drugs, administered intravenously, against the bacteria causing the infection. Initial treatment should always comprise a new generation cephalosporin (with or without Vancomycin) plus dexamethasone unless the patient is already under a specific antibiotic regimen.The use of penicillins is limited due to their suboptimal penetration into the CSF. Early intravenous administration of dexamethasone is currently recommended as adjunctive therapy in an attempt to diminish the rate of permanent neurological sequelae. Antibiotic treatment is modified based on the CSF culture and antibiotic sensibility studies.Family members of those infected can be treated with Rifampin as a preventative measure; however, for pregnant women, ceftriaxone is recommended.
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Therapies of Meningococcal Meningitis. TreatmentThere are 5 subtypes of N. meningitidis. Currently, (as of June, 2012) licensed vaccines for prevention of illness from 4 of the 5 subtypes exists. The vaccines are called Menveo, Menactra and Nimerix. Vaccines with narrow coverage have been used against serogroup B, and a vaccine with broad coverage is in late stage of development. Public health officials recommend that all college students take the meningococcal meningitis immunization. In particular, those who live in close quarters (dormitories, fraternities, and sororities), who frequent bars or consume alcohol, who smoke or are regularly around smokers are at higher risk and should consider vaccination. Students with certain chronic conditions (eg, have had their spleen removed) should be vaccinated. Students traveling to high-risk areas of the world (eg, sub-Sahara Africa) should consider vaccination. The conjugate vaccine is now also recommended for all children when they reach 11-12 years of age.Meningococcal meningitis is usually treated with antibiotic drugs, administered intravenously, against the bacteria causing the infection. Initial treatment should always comprise a new generation cephalosporin (with or without Vancomycin) plus dexamethasone unless the patient is already under a specific antibiotic regimen.The use of penicillins is limited due to their suboptimal penetration into the CSF. Early intravenous administration of dexamethasone is currently recommended as adjunctive therapy in an attempt to diminish the rate of permanent neurological sequelae. Antibiotic treatment is modified based on the CSF culture and antibiotic sensibility studies.Family members of those infected can be treated with Rifampin as a preventative measure; however, for pregnant women, ceftriaxone is recommended.
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Meningococcal Meningitis
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Overview of Meningococcemia
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Meningococcemia is a rare infectious disease characterized by upper respiratory tract infection, fever, skin rash and lesions, eye and ear problems, and possibly a sudden state of extreme physical depression (shock) which may be life-threatening without appropriate medical care. There are two forms of meningococcemia. Fluminant meningococcemia develops very rapidly and is more severe than chronic meningococcemia, which has a waxing and waning course.
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Overview of Meningococcemia. Meningococcemia is a rare infectious disease characterized by upper respiratory tract infection, fever, skin rash and lesions, eye and ear problems, and possibly a sudden state of extreme physical depression (shock) which may be life-threatening without appropriate medical care. There are two forms of meningococcemia. Fluminant meningococcemia develops very rapidly and is more severe than chronic meningococcemia, which has a waxing and waning course.
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Meningococcemia
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Symptoms of Meningococcemia
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Meningococcemia is characterized by sudden intense headache, nausea, fever, vomiting, and skin rash. The affected individual may first complain of an upper respiratory infection. Chills may develop, then skin rash on the arms or legs and the trunk. Diarrhea may also be present. Later the rash may become widespread or develop into bleeding spots under the skin (petechiae, ecchymoses, or purpura). There may be associated swelling, muscle pain, skin deterioration or gangrene in the arms and legs. Pneumonia may also develop along with the other symptoms if the affected individual has a suppressed immune system.In cases where meningitis occurs along with meningococcemia, the affected individual may have the symptoms listed above along with the combination of headache, confusion, stiff neck, and muscle pain from irritation of membranes surrounding the brain and spinal cord (meningismus). (For more information on this disorder, choose “Meningitis” as your search term in the Rare Disease Database).Fulminant Meningococcemia is also known as Waterhouse-Friderichsen Syndrome and is the most severe form of the disorder. The disease comes on very suddenly and the progression of the symptoms is very rapid. In less than a few hours the affected individual may experience very high fever, chills, weakness, vomiting and severe headache. A red rash appears on the arms and legs and spreads very quickly over the body including the eyes and nose. In addition, the affected individuals blood pressure may drop dangerously, the fever may drop dramatically, and they may go into shock. Without immediate medical treatment this disorder can be life-threatening.Chronic Meningococcemia is a rarer form of the disease. It is characterized by fever that comes and goes over a period of weeks or months. Muscle and joint pain with headache as well as a skin rash may also come and go. This form of the disorder may also include an enlarged spleen.
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Symptoms of Meningococcemia. Meningococcemia is characterized by sudden intense headache, nausea, fever, vomiting, and skin rash. The affected individual may first complain of an upper respiratory infection. Chills may develop, then skin rash on the arms or legs and the trunk. Diarrhea may also be present. Later the rash may become widespread or develop into bleeding spots under the skin (petechiae, ecchymoses, or purpura). There may be associated swelling, muscle pain, skin deterioration or gangrene in the arms and legs. Pneumonia may also develop along with the other symptoms if the affected individual has a suppressed immune system.In cases where meningitis occurs along with meningococcemia, the affected individual may have the symptoms listed above along with the combination of headache, confusion, stiff neck, and muscle pain from irritation of membranes surrounding the brain and spinal cord (meningismus). (For more information on this disorder, choose “Meningitis” as your search term in the Rare Disease Database).Fulminant Meningococcemia is also known as Waterhouse-Friderichsen Syndrome and is the most severe form of the disorder. The disease comes on very suddenly and the progression of the symptoms is very rapid. In less than a few hours the affected individual may experience very high fever, chills, weakness, vomiting and severe headache. A red rash appears on the arms and legs and spreads very quickly over the body including the eyes and nose. In addition, the affected individuals blood pressure may drop dangerously, the fever may drop dramatically, and they may go into shock. Without immediate medical treatment this disorder can be life-threatening.Chronic Meningococcemia is a rarer form of the disease. It is characterized by fever that comes and goes over a period of weeks or months. Muscle and joint pain with headache as well as a skin rash may also come and go. This form of the disorder may also include an enlarged spleen.
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Meningococcemia
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Causes of Meningococcemia
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Meningococcemia is caused by infection with the meningococci bacteria (Neisseria memingitidis) which are gram-negative diplococci bacteria. There are various groups of this bacteria that cause different forms of the disease and they are grouped by strains A, B, C, D, X, Y, Z, 29E and W135. These groups can be identified by testing the blood, scrapings of the skin rash and samples of the cerebrospinal fluid of the patient. Testing may take up to five days as the cultures are very slow growing.Infection with the bacteria is usually caused by a carrier. The natural place for the bacteria to be located is in either the nose or throat of the carrier, and they can be spread the infection through airborne or close contact methods. The carrier may spread the infection for weeks or months if they are not diagnosed and treated.
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Causes of Meningococcemia. Meningococcemia is caused by infection with the meningococci bacteria (Neisseria memingitidis) which are gram-negative diplococci bacteria. There are various groups of this bacteria that cause different forms of the disease and they are grouped by strains A, B, C, D, X, Y, Z, 29E and W135. These groups can be identified by testing the blood, scrapings of the skin rash and samples of the cerebrospinal fluid of the patient. Testing may take up to five days as the cultures are very slow growing.Infection with the bacteria is usually caused by a carrier. The natural place for the bacteria to be located is in either the nose or throat of the carrier, and they can be spread the infection through airborne or close contact methods. The carrier may spread the infection for weeks or months if they are not diagnosed and treated.
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Meningococcemia
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Affects of Meningococcemia
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Meningococcemia affects males and females in equal numbers. However, most cases develop in persons twenty years of age or younger and half of these cases are in children under five years of age. In the United States 1.2 cases per 100,000 occur annually. Winter and spring are the most common seasons of the year when cases are reported. Epidemics can occur under crowded conditions and tend to occur at 20 to 30 year intervals. In other parts of the world epidemics are usually caused by the Group A strain of the bacteria. During epidemics, rates of 5 to 24 cases per 100,000 persons have occurred. In Sao Paulo, Brazil, during 1974 the epidemic rate was 370 per 100,000 persons infected with Meningococcemia. In the United States, the most prevalent Group strains of the bacteria are B,C,Y, and W-135.
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Affects of Meningococcemia. Meningococcemia affects males and females in equal numbers. However, most cases develop in persons twenty years of age or younger and half of these cases are in children under five years of age. In the United States 1.2 cases per 100,000 occur annually. Winter and spring are the most common seasons of the year when cases are reported. Epidemics can occur under crowded conditions and tend to occur at 20 to 30 year intervals. In other parts of the world epidemics are usually caused by the Group A strain of the bacteria. During epidemics, rates of 5 to 24 cases per 100,000 persons have occurred. In Sao Paulo, Brazil, during 1974 the epidemic rate was 370 per 100,000 persons infected with Meningococcemia. In the United States, the most prevalent Group strains of the bacteria are B,C,Y, and W-135.
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Meningococcemia
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Related disorders of Meningococcemia
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Symptoms of the following disorders can be similar to those of Meningococcemia. Comparisons may be useful for a differential diagnosis:Rocky Mountain Spotted Fever is a tick-borne disease that begins with an incubation period of from two to twelve days. A gradually or abruptly beginning fever may be followed after three to five days by a pink or purplish colored rash on the wrists and ankles. The fever and rash usually become more severe for seven to fourteen days. The rash may not develop in all cases, possibly making diagnosis difficult. A blood test is necessary to confirm the diagnosis. (For more information on this disorder, choose “Rocky Mountain” as your search term in the Rare Disease Database.)Henoch-Shonlein Purpura is one of a group of disorders characterized by purplish or brownish red discolorations on the skin. These spots may be large or small. Internal bleeding may occur in various areas of the body. This blood vessel disorder may affect the skin, joints, gastrointestinal system, kidneys, and in a very few cases the central nervous system. (For more information on this disorder, choose “Henoch-Shonlein” as your search term in the Rare Disease Database.)Rheumatic Fever is an inflammatory syndrome that can occur following a streptococcal infection. Patients initially experience moderate fever, a general feeling of ill health, a sore throat, fatigue and a red rash. Major complications can include heart disease, joint pain and arthritis, involuntary abrupt limb movements with characteristic grimaces and skin symptoms. (For more information on this disorder, choose “Rheumatic” as your search term in the Rare Disease Database.)Toxic Shock Syndrome symptoms appear very suddenly. Initially, there is a fever of 102 to 105 degrees F, headache, sore throat, and conjunctivitis. Other early symptoms include profound lethargy, periods of disorientation, vomiting, severe diarrhea, and a diffuse sunburn-like rash leading to sloughing of skin after several days. In severe cases, the syndrome may progress to shock (dangerously low blood pressure and circulatory collapse) within forty-eight hours. (For more information on this disorder, choose “Toxic Shock” as your search term in the Rare Disease Database.)Infective Endocarditis usually has a very sudden onset. Complaints of low back pain, pain in the joints (arthralgia) or in one or more muscles (myalgia) are common. These symptoms usually appear early in the disease, occasionally as the only initial symptoms. Fever, night sweats, chills, headache and loss of appetite may also occur. Blood or blood cells may be present in the urine (hematuria), small red or purple spots composed of blood (petechiae) may cover the skin of the upper trunk and there may also be pale, oval spots on the retina of the eye. (For more information on this disorder, choose “Endocarditis” as your search term in the Rare Disease Database.)
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Related disorders of Meningococcemia. Symptoms of the following disorders can be similar to those of Meningococcemia. Comparisons may be useful for a differential diagnosis:Rocky Mountain Spotted Fever is a tick-borne disease that begins with an incubation period of from two to twelve days. A gradually or abruptly beginning fever may be followed after three to five days by a pink or purplish colored rash on the wrists and ankles. The fever and rash usually become more severe for seven to fourteen days. The rash may not develop in all cases, possibly making diagnosis difficult. A blood test is necessary to confirm the diagnosis. (For more information on this disorder, choose “Rocky Mountain” as your search term in the Rare Disease Database.)Henoch-Shonlein Purpura is one of a group of disorders characterized by purplish or brownish red discolorations on the skin. These spots may be large or small. Internal bleeding may occur in various areas of the body. This blood vessel disorder may affect the skin, joints, gastrointestinal system, kidneys, and in a very few cases the central nervous system. (For more information on this disorder, choose “Henoch-Shonlein” as your search term in the Rare Disease Database.)Rheumatic Fever is an inflammatory syndrome that can occur following a streptococcal infection. Patients initially experience moderate fever, a general feeling of ill health, a sore throat, fatigue and a red rash. Major complications can include heart disease, joint pain and arthritis, involuntary abrupt limb movements with characteristic grimaces and skin symptoms. (For more information on this disorder, choose “Rheumatic” as your search term in the Rare Disease Database.)Toxic Shock Syndrome symptoms appear very suddenly. Initially, there is a fever of 102 to 105 degrees F, headache, sore throat, and conjunctivitis. Other early symptoms include profound lethargy, periods of disorientation, vomiting, severe diarrhea, and a diffuse sunburn-like rash leading to sloughing of skin after several days. In severe cases, the syndrome may progress to shock (dangerously low blood pressure and circulatory collapse) within forty-eight hours. (For more information on this disorder, choose “Toxic Shock” as your search term in the Rare Disease Database.)Infective Endocarditis usually has a very sudden onset. Complaints of low back pain, pain in the joints (arthralgia) or in one or more muscles (myalgia) are common. These symptoms usually appear early in the disease, occasionally as the only initial symptoms. Fever, night sweats, chills, headache and loss of appetite may also occur. Blood or blood cells may be present in the urine (hematuria), small red or purple spots composed of blood (petechiae) may cover the skin of the upper trunk and there may also be pale, oval spots on the retina of the eye. (For more information on this disorder, choose “Endocarditis” as your search term in the Rare Disease Database.)
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Meningococcemia
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Diagnosis of Meningococcemia
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The diagnosis of Meningococcemia may be confirmed by a thorough clinical evaluation and specialized blood tests.
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Diagnosis of Meningococcemia. The diagnosis of Meningococcemia may be confirmed by a thorough clinical evaluation and specialized blood tests.
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Meningococcemia
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Therapies of Meningococcemia
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TreatmentMeningococcemia is usually treated with Penicillin or Ampicillin. In adults the method of treatment is often through intravenous Penicillin G. In children penicillin is still the treatment of choice, however, other organisms must be ruled out before treatment is begun. For persons who are unable to take penicillin, other antibiotics are used such as: cefuroxime, cefotaxime or ceftriaxone.In persons who survive severe meningococcal septicemia there may be ongoing problems with veins and arteries. There are usually serious orthopedic problems. If gangrene occurs amputation may be necessary. These patients should have continuing medical evaluations as a precaution against other conditions that can arise in later years.During times of epidemics, prophylaxis with other antibiotics (i.e., Rifampin, minocycline, and sulfadiazine) is used to protect persons exposed to or in close contact with infected patients.
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Therapies of Meningococcemia. TreatmentMeningococcemia is usually treated with Penicillin or Ampicillin. In adults the method of treatment is often through intravenous Penicillin G. In children penicillin is still the treatment of choice, however, other organisms must be ruled out before treatment is begun. For persons who are unable to take penicillin, other antibiotics are used such as: cefuroxime, cefotaxime or ceftriaxone.In persons who survive severe meningococcal septicemia there may be ongoing problems with veins and arteries. There are usually serious orthopedic problems. If gangrene occurs amputation may be necessary. These patients should have continuing medical evaluations as a precaution against other conditions that can arise in later years.During times of epidemics, prophylaxis with other antibiotics (i.e., Rifampin, minocycline, and sulfadiazine) is used to protect persons exposed to or in close contact with infected patients.
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Meningococcemia
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Overview of Menkes Disease
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IntroductionMenkes disease (MD) is an inherited X-linked recessive disorder that affects many systems in the body. Affected infants are often born prematurely and may have non-specific symptoms such as hypothermia, hypoglycemia, and prolonged jaundice. One obvious and specific physical sign is “steely” or “kinky” hair that usually develops by several months of age. Menkes disease is also associated with seizures, stunted growth, failure to thrive, unstable body temperature, and intellectual disability.Menkes disease is caused by mutations in the ATP7A gene that is responsible for transport of copper throughout the body. The body uses copper as a cofactor to activate certain enzymes in order to carry out certain functions. When these enzymes are not working normally, serious and fatal effects can ensue over time related to the function of the copper-dependent enzymes that control the development of hair, brain, bones, liver, and arteries. Variants of MD that are caused by mutations in the ATP7A gene but result in less severe symptoms include mild Menkes disease and occipital horn syndrome.There is no complete cure for Menkes disease at this time, but treatment with parenteral copper histidinate (CuHis) can increase survival and lessen the neurological symptoms if initiated early, within approximately 28 days following birth.
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Overview of Menkes Disease. IntroductionMenkes disease (MD) is an inherited X-linked recessive disorder that affects many systems in the body. Affected infants are often born prematurely and may have non-specific symptoms such as hypothermia, hypoglycemia, and prolonged jaundice. One obvious and specific physical sign is “steely” or “kinky” hair that usually develops by several months of age. Menkes disease is also associated with seizures, stunted growth, failure to thrive, unstable body temperature, and intellectual disability.Menkes disease is caused by mutations in the ATP7A gene that is responsible for transport of copper throughout the body. The body uses copper as a cofactor to activate certain enzymes in order to carry out certain functions. When these enzymes are not working normally, serious and fatal effects can ensue over time related to the function of the copper-dependent enzymes that control the development of hair, brain, bones, liver, and arteries. Variants of MD that are caused by mutations in the ATP7A gene but result in less severe symptoms include mild Menkes disease and occipital horn syndrome.There is no complete cure for Menkes disease at this time, but treatment with parenteral copper histidinate (CuHis) can increase survival and lessen the neurological symptoms if initiated early, within approximately 28 days following birth.
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Menkes Disease
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Symptoms of Menkes Disease
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Menkes disease is characterized by dry skin and abnormal hair that is often brittle, tangled, sparse, steely or kinky and is often white, ivory, or grey in color. The affected infant may also appear to have a yellow appearance (jaundice) which is caused by excessive bilirubin in the blood (hyperbilirubinemia). Lower than normal body temperature (hypothermia) also may occur in the neonatal period. The normal, asymptomatic phase of the illness typically lasts for two to three months.Brain and cognitive abnormalities are central in this disorder. Blood clots (subdural hematomas) and/or rupture or thrombosis of arteries in the brain may occur. Neurodegenerative effects such as seizures, and delayed growth and development may also arise. Reduced bone density (osteoporosis) is common and may result in fractures. The combination of subdural hematoma and bone fractures may lead to an incorrect diagnosis of child abuse. Emphysema, bladder diverticula, neck masses due to internal jugular vein phlebectasia, and cortical blindness have also been described.Occipital horn syndrome (OHS) is recognized as a milder form of MD with less severe neurological involvement and is usually diagnosed around the age of 5-10 years.
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Symptoms of Menkes Disease. Menkes disease is characterized by dry skin and abnormal hair that is often brittle, tangled, sparse, steely or kinky and is often white, ivory, or grey in color. The affected infant may also appear to have a yellow appearance (jaundice) which is caused by excessive bilirubin in the blood (hyperbilirubinemia). Lower than normal body temperature (hypothermia) also may occur in the neonatal period. The normal, asymptomatic phase of the illness typically lasts for two to three months.Brain and cognitive abnormalities are central in this disorder. Blood clots (subdural hematomas) and/or rupture or thrombosis of arteries in the brain may occur. Neurodegenerative effects such as seizures, and delayed growth and development may also arise. Reduced bone density (osteoporosis) is common and may result in fractures. The combination of subdural hematoma and bone fractures may lead to an incorrect diagnosis of child abuse. Emphysema, bladder diverticula, neck masses due to internal jugular vein phlebectasia, and cortical blindness have also been described.Occipital horn syndrome (OHS) is recognized as a milder form of MD with less severe neurological involvement and is usually diagnosed around the age of 5-10 years.
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Menkes Disease
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Causes of Menkes Disease
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Menkes disease is an X-linked genetic disorder caused by mutations in the ATP7A gene. This gene is responsible for production of the ATPase enzyme that regulates copper levels in the body. Individuals with Menkes disease have an abnormally low level of copper in the brain and liver and excess copper in the intestines and kidneys. Without the copper as a key element in their structure and functioning, the activity of the body’s copper-dependent enzymes is diminished. For example, reduced activity of the cuproenzyme tyrosinase causes reduced pigmentation of the hair and skin. Reduced activity of the cuproenzyme lysine oxidase causes failure of connective tissue to form strong, inner blood vessels walls. X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the non-working gene. However, since males have one X chromosome, inherited from the mother, if a male inherits an X chromosome harboring a non-working gene, he will develop the disease. Female carriers of an X-linked disorder have a 50% chance to have a son affected with the disease and a 50% chance of an unaffected son. There is a 50% chance with each pregnancy to have asymptomatic “carrier” daughter like themselves, and a 50% chance to have a non-carrier daughter. If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his 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.
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Causes of Menkes Disease. Menkes disease is an X-linked genetic disorder caused by mutations in the ATP7A gene. This gene is responsible for production of the ATPase enzyme that regulates copper levels in the body. Individuals with Menkes disease have an abnormally low level of copper in the brain and liver and excess copper in the intestines and kidneys. Without the copper as a key element in their structure and functioning, the activity of the body’s copper-dependent enzymes is diminished. For example, reduced activity of the cuproenzyme tyrosinase causes reduced pigmentation of the hair and skin. Reduced activity of the cuproenzyme lysine oxidase causes failure of connective tissue to form strong, inner blood vessels walls. X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the non-working gene. However, since males have one X chromosome, inherited from the mother, if a male inherits an X chromosome harboring a non-working gene, he will develop the disease. Female carriers of an X-linked disorder have a 50% chance to have a son affected with the disease and a 50% chance of an unaffected son. There is a 50% chance with each pregnancy to have asymptomatic “carrier” daughter like themselves, and a 50% chance to have a non-carrier daughter. If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his 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.
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Menkes Disease
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Affects of Menkes Disease
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Recent studies suggest that the incidence of Menkes disease is about 1 in 35,000 live male births. The majority of diagnosed infants are male; however, MD may still occur in females, related to unusual genetic circumstances.
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Affects of Menkes Disease. Recent studies suggest that the incidence of Menkes disease is about 1 in 35,000 live male births. The majority of diagnosed infants are male; however, MD may still occur in females, related to unusual genetic circumstances.
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Menkes Disease
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Related disorders of Menkes Disease
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Wilson disease is a genetic disorder of copper metabolism characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. The disease is progressive and if left untreated, may cause liver (hepatic) failure, hemolytic crisis, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life-threatening complications. Treatment is aimed at reducing the amount of copper accumulated in the body by chelation therapy and maintaining normal copper levels thereafter. (For more information on this disorder, please choose “Wilson” as your search term in the Rare Disease Database.)
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Related disorders of Menkes Disease. Wilson disease is a genetic disorder of copper metabolism characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. The disease is progressive and if left untreated, may cause liver (hepatic) failure, hemolytic crisis, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life-threatening complications. Treatment is aimed at reducing the amount of copper accumulated in the body by chelation therapy and maintaining normal copper levels thereafter. (For more information on this disorder, please choose “Wilson” as your search term in the Rare Disease Database.)
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Menkes Disease
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Diagnosis of Menkes Disease
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The diagnosis of MD is suggested by the appearance of brittle, tangled, sparse, steely or kinky hair at several months of age. Blood tests showing low levels of serum copper and ceruloplasmin support the diagnosis. It is important to note that these levels are typically low in otherwise healthy newborns. A new method of diagnosis that can potential identify affected infants before copper deficiency affects the brain involves measurement of plasma catecholamine levels. This may be the basis for Menkes disease newborn screening in the future. Molecular genetic testing for mutations in the ATP7A gene may also prove to be an efficient method of population-based newborn screening. For infants suspected to be affected on clinical and biochemical grounds, ATP7A mutation testing is available commercially to confirm the diagnosis. Carrier testing and prenatal diagnosis are also available once a specific ATP7A gene variant has been identified in an affected family member.
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Diagnosis of Menkes Disease. The diagnosis of MD is suggested by the appearance of brittle, tangled, sparse, steely or kinky hair at several months of age. Blood tests showing low levels of serum copper and ceruloplasmin support the diagnosis. It is important to note that these levels are typically low in otherwise healthy newborns. A new method of diagnosis that can potential identify affected infants before copper deficiency affects the brain involves measurement of plasma catecholamine levels. This may be the basis for Menkes disease newborn screening in the future. Molecular genetic testing for mutations in the ATP7A gene may also prove to be an efficient method of population-based newborn screening. For infants suspected to be affected on clinical and biochemical grounds, ATP7A mutation testing is available commercially to confirm the diagnosis. Carrier testing and prenatal diagnosis are also available once a specific ATP7A gene variant has been identified in an affected family member.
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Menkes Disease
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Therapies of Menkes Disease
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Treatment
Early (ideally within 28 days of age of birth, corrected for prematurity) treatment of Menkes disease is essential. Injections of a copper histidinate (CuHis), a new molecular entity prepared as a freeze-dried product, have been shown to increase the concentration of copper in the blood and improve neurodevelopmental outcomes in some patients. The degree of CuHis treatment efficacy in older, symptomatic Menkes disease patients is less clear. Genetic counseling is recommended for the parents and families of affected children for a proper understanding of recurrence risk.
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Therapies of Menkes Disease. Treatment
Early (ideally within 28 days of age of birth, corrected for prematurity) treatment of Menkes disease is essential. Injections of a copper histidinate (CuHis), a new molecular entity prepared as a freeze-dried product, have been shown to increase the concentration of copper in the blood and improve neurodevelopmental outcomes in some patients. The degree of CuHis treatment efficacy in older, symptomatic Menkes disease patients is less clear. Genetic counseling is recommended for the parents and families of affected children for a proper understanding of recurrence risk.
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Menkes Disease
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nord_798_0
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Overview of Merkel Cell Carcinoma
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SummaryMerkel cell carcinoma (MCC) is a rare form of skin cancer. It is an aggressive type of cancer that can spread (metastasize) to other areas of the body. The exact, underlying cause of the disease is not known, but there are several factors, including environmental and immunologic ones, that contribute to the development of the disease. Treatment guidelines are rapidly evolving with new studies and treatment options. Clinical features, tests for diagnosis and treatment options are discussed below. MCC is characterized as a neuroendocrine carcinoma because it involves interaction between the nervous system and the endocrine system.
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Overview of Merkel Cell Carcinoma. SummaryMerkel cell carcinoma (MCC) is a rare form of skin cancer. It is an aggressive type of cancer that can spread (metastasize) to other areas of the body. The exact, underlying cause of the disease is not known, but there are several factors, including environmental and immunologic ones, that contribute to the development of the disease. Treatment guidelines are rapidly evolving with new studies and treatment options. Clinical features, tests for diagnosis and treatment options are discussed below. MCC is characterized as a neuroendocrine carcinoma because it involves interaction between the nervous system and the endocrine system.
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Merkel Cell Carcinoma
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Symptoms of Merkel Cell Carcinoma
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Merkel cell carcinoma most commonly affects regions of the skin that are exposed to the sun including the head/neck and arms, but it can also develop on other areas of the body that are not typically sun-exposed.In most people, the first sign of Merkel cell carcinoma is a small bump (nodule) on the skin. This bump is usually firm and appears either skin-colored or red-purple. Sometimes, the nodule can have a shiny surface or be covered with small widened (dilated) vessels. It also tends to grow rapidly. Often, there are no symptoms associated with the nodule. Although uncommon for MCC, the abnormal growth can rip open (ulcerate) to form an open sore with crusting. The acronym ‘AEIOU’ can be used to note characteristic clinical findings. The acronym stands for: asymptomatic (no noticeable symptoms); expanding rapidly (within 3 months’ times); immune suppression; older than 50 years of age; and ultraviolet light-exposed area affecting a fair-skinned individual.In some instances, lymph node(s) to which the primary lesion drains, can become enlarged (lymphadenopathy). This is a clinical indication (via palpation and/or imaging) that the disease has spread to the patient’s nearby (regional) lymph node bed. This can occur in patients who present with a primary skin lesion as well as in those who do not. Individuals affected by MCC without a primary tumor (no original skin lesion) tend to do better compared to patients with primary tumor as well aslymph node involvement because it is likely that their immune system was able to eliminate the primary lesion and are thus more likely to be able to eliminate small numbers of undetected MCC cells that may be present elsewhere in the body.Larger MCC tumors are associated with moderately higher risk of recurrence and spreading to lymph nodes. However, even small MCC tumors carry about a 25% risk of spreading to nearby lymph nodes. Merkel cell carcinoma can also spread to other areas of the body, like the liver, bones, pancreas and other skin/body wall locations.
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Symptoms of Merkel Cell Carcinoma. Merkel cell carcinoma most commonly affects regions of the skin that are exposed to the sun including the head/neck and arms, but it can also develop on other areas of the body that are not typically sun-exposed.In most people, the first sign of Merkel cell carcinoma is a small bump (nodule) on the skin. This bump is usually firm and appears either skin-colored or red-purple. Sometimes, the nodule can have a shiny surface or be covered with small widened (dilated) vessels. It also tends to grow rapidly. Often, there are no symptoms associated with the nodule. Although uncommon for MCC, the abnormal growth can rip open (ulcerate) to form an open sore with crusting. The acronym ‘AEIOU’ can be used to note characteristic clinical findings. The acronym stands for: asymptomatic (no noticeable symptoms); expanding rapidly (within 3 months’ times); immune suppression; older than 50 years of age; and ultraviolet light-exposed area affecting a fair-skinned individual.In some instances, lymph node(s) to which the primary lesion drains, can become enlarged (lymphadenopathy). This is a clinical indication (via palpation and/or imaging) that the disease has spread to the patient’s nearby (regional) lymph node bed. This can occur in patients who present with a primary skin lesion as well as in those who do not. Individuals affected by MCC without a primary tumor (no original skin lesion) tend to do better compared to patients with primary tumor as well aslymph node involvement because it is likely that their immune system was able to eliminate the primary lesion and are thus more likely to be able to eliminate small numbers of undetected MCC cells that may be present elsewhere in the body.Larger MCC tumors are associated with moderately higher risk of recurrence and spreading to lymph nodes. However, even small MCC tumors carry about a 25% risk of spreading to nearby lymph nodes. Merkel cell carcinoma can also spread to other areas of the body, like the liver, bones, pancreas and other skin/body wall locations.
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Merkel Cell Carcinoma
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Causes of Merkel Cell Carcinoma
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Several risk factors have been established for MCC. These include being over the age of 50, having fair-skin, experiencing extensive sun exposure (ultraviolet light), or having an immune system that is either weakened or compromised. Individuals with conditions that suppress the immune system are at elevated risk of developing MCC. However, over 90% of people with MCC do not have any known problem with their immune system.Researchers have determined that Merkel cell carcinoma is frequently associated (~80%) with a virus called Merkel cell polyomavirus (MCPyV). It is now clear that the majority of people become infected with MCPyV by adulthood, but it appears that the virus does not cause any symptoms except in the very rare situations in which it much later leads to MCC. In addition, some individuals develop Merkel cell carcinoma without the presence of the Merkel cell polyomavirus (~20%), and such cases are usually associated with extensive UV exposure.
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Causes of Merkel Cell Carcinoma. Several risk factors have been established for MCC. These include being over the age of 50, having fair-skin, experiencing extensive sun exposure (ultraviolet light), or having an immune system that is either weakened or compromised. Individuals with conditions that suppress the immune system are at elevated risk of developing MCC. However, over 90% of people with MCC do not have any known problem with their immune system.Researchers have determined that Merkel cell carcinoma is frequently associated (~80%) with a virus called Merkel cell polyomavirus (MCPyV). It is now clear that the majority of people become infected with MCPyV by adulthood, but it appears that the virus does not cause any symptoms except in the very rare situations in which it much later leads to MCC. In addition, some individuals develop Merkel cell carcinoma without the presence of the Merkel cell polyomavirus (~20%), and such cases are usually associated with extensive UV exposure.
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Merkel Cell Carcinoma
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Affects of Merkel Cell Carcinoma
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Approximately 60% of MCC tumors arise in men. In the past 15 years, the incidence has tripled in the United States, and it can be lethal for about one-third of the people affected. As of 2020, approximately 3,000 persons per year are diagnosed with this cancer in the United States. The projected incidence is 3,200 cases by the year 2025.The incidence (number of people who develop a disorder over a given period of time such as one year) is approximately 0.7 people per 100,000 people in the general population of the United States. It dramatically increases to approximately 9.8 people per 100,000 in individuals more than 85 years of age. There is a 100,000-fold difference between the risk of developing MCC for patients under the age of 30 compared to those who are greater than 85 years old.
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Affects of Merkel Cell Carcinoma. Approximately 60% of MCC tumors arise in men. In the past 15 years, the incidence has tripled in the United States, and it can be lethal for about one-third of the people affected. As of 2020, approximately 3,000 persons per year are diagnosed with this cancer in the United States. The projected incidence is 3,200 cases by the year 2025.The incidence (number of people who develop a disorder over a given period of time such as one year) is approximately 0.7 people per 100,000 people in the general population of the United States. It dramatically increases to approximately 9.8 people per 100,000 in individuals more than 85 years of age. There is a 100,000-fold difference between the risk of developing MCC for patients under the age of 30 compared to those who are greater than 85 years old.
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Merkel Cell Carcinoma
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Related disorders of Merkel Cell Carcinoma
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There are many different conditions that have an appearance very similar to Merkel cell carcinoma. These include epidermoid cysts, squamous cell carcinoma, basal cell carcinoma, pyogenic granuloma, lipomas, adnexal tumors, sebaceous cysts, melanoma and lymphoma. Under a microscope, small cell carcinoma of the lung is often a difficult disease to differentiate from primary Merkel cell carcinoma. Both cancers have similar neuroendocrine features. As such, special stains must be carried out in order to distinguish one cancer form from the other. This procedure is called immunostaining. During immunostaining, antibodies are applied to a sample of the tumor from a biopsy or from surgical removal. The antibodies are used to test for certain proteins (markers). Typically, MCC tumors stain positive for low molecular weight cytokeratins (CAM 5.2 or AE1/AE3), CK20 and neuron-specific enolase (NSE). MCC is typically not positive for CK7 or thyroid transcription factor 1 (TTF-1).
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Related disorders of Merkel Cell Carcinoma. There are many different conditions that have an appearance very similar to Merkel cell carcinoma. These include epidermoid cysts, squamous cell carcinoma, basal cell carcinoma, pyogenic granuloma, lipomas, adnexal tumors, sebaceous cysts, melanoma and lymphoma. Under a microscope, small cell carcinoma of the lung is often a difficult disease to differentiate from primary Merkel cell carcinoma. Both cancers have similar neuroendocrine features. As such, special stains must be carried out in order to distinguish one cancer form from the other. This procedure is called immunostaining. During immunostaining, antibodies are applied to a sample of the tumor from a biopsy or from surgical removal. The antibodies are used to test for certain proteins (markers). Typically, MCC tumors stain positive for low molecular weight cytokeratins (CAM 5.2 or AE1/AE3), CK20 and neuron-specific enolase (NSE). MCC is typically not positive for CK7 or thyroid transcription factor 1 (TTF-1).
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Merkel Cell Carcinoma
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Diagnosis of Merkel Cell Carcinoma
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Diagnosis
A diagnosis of Merkel cell carcinoma is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests.Clinical Testing and Workup
A doctor may remove a small sample of affected skin to be studied under a microscope, also known as a biopsy. The most common types of biopsies include a shave biopsy (part of the top of the abnormal tissue is removed with a scalpel) or a punch biopsy (a small cylinder of tissue is removed). The sample is then examined by a pathologist, who is a specialist trained in examining tissues and cells to understand the basis of the disease.To ensure proper care for MCC, doctors typically perform a sentinel lymph node biopsy (SLNB) to determine whether the cancer has spread to draining lymph nodes. A sentinel lymph node biopsy is used to determine the first lymph nodes to which the cancer may have spread. This technique is used to identify the sentinel lymph node (draining lymph node basin). This procedure is carried out in the operating room. During this procedure, a doctor will inject radioactive dye into the site of the primary lesion. The dye will then travel to, and collect in, the sentinel lymph node. Doctors will be able to see this through a special probe that can view the radioactive dye. The sentinel lymph node is then removed and examined carefully under a microscope for even a small number of MCC tumor cells.Imaging techniques including positron emission tomography (PET), computed tomography (CT) and occasionally magnetic resonance imaging (MRI) are used to see whether the cancer has spread. Doctors often will recommend a combined PET/CT scan. This scan gathers information about how much metabolic activity (glucose uptake, measured by PET) a cancer has at the same time as mapping the adjacent body structures (CT). PET/CT has higher sensitivity compared to CT scans alone and is often the favored imaging modality for scans to determine the stage of the cancer.
MCC has a higher propensity to have metastasized at diagnosis compared to other skin cancers. Nearly 1 in every 6 MCC patients are upstaged by baseline imaging, compared to <1% of melanoma patients.
Staging
When an individual is diagnosed with Merkel cell carcinoma, additional studies are required to determine the extent or “stage” of the disease. Staging is important to help characterize the potential disease course and determine appropriate treatment approaches. A variety of diagnostic tests may be used in staging Merkel cell carcinoma (e.g., blood tests, SLNB, CT scan) as noted above. Merkel cell carcinoma has an established, worldwide consensus staging system. This staging system is summarized at:
https://www.merkelcell.org/testing-and-diagnosis/staging/
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Diagnosis of Merkel Cell Carcinoma. Diagnosis
A diagnosis of Merkel cell carcinoma is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests.Clinical Testing and Workup
A doctor may remove a small sample of affected skin to be studied under a microscope, also known as a biopsy. The most common types of biopsies include a shave biopsy (part of the top of the abnormal tissue is removed with a scalpel) or a punch biopsy (a small cylinder of tissue is removed). The sample is then examined by a pathologist, who is a specialist trained in examining tissues and cells to understand the basis of the disease.To ensure proper care for MCC, doctors typically perform a sentinel lymph node biopsy (SLNB) to determine whether the cancer has spread to draining lymph nodes. A sentinel lymph node biopsy is used to determine the first lymph nodes to which the cancer may have spread. This technique is used to identify the sentinel lymph node (draining lymph node basin). This procedure is carried out in the operating room. During this procedure, a doctor will inject radioactive dye into the site of the primary lesion. The dye will then travel to, and collect in, the sentinel lymph node. Doctors will be able to see this through a special probe that can view the radioactive dye. The sentinel lymph node is then removed and examined carefully under a microscope for even a small number of MCC tumor cells.Imaging techniques including positron emission tomography (PET), computed tomography (CT) and occasionally magnetic resonance imaging (MRI) are used to see whether the cancer has spread. Doctors often will recommend a combined PET/CT scan. This scan gathers information about how much metabolic activity (glucose uptake, measured by PET) a cancer has at the same time as mapping the adjacent body structures (CT). PET/CT has higher sensitivity compared to CT scans alone and is often the favored imaging modality for scans to determine the stage of the cancer.
MCC has a higher propensity to have metastasized at diagnosis compared to other skin cancers. Nearly 1 in every 6 MCC patients are upstaged by baseline imaging, compared to <1% of melanoma patients.
Staging
When an individual is diagnosed with Merkel cell carcinoma, additional studies are required to determine the extent or “stage” of the disease. Staging is important to help characterize the potential disease course and determine appropriate treatment approaches. A variety of diagnostic tests may be used in staging Merkel cell carcinoma (e.g., blood tests, SLNB, CT scan) as noted above. Merkel cell carcinoma has an established, worldwide consensus staging system. This staging system is summarized at:
https://www.merkelcell.org/testing-and-diagnosis/staging/
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Merkel Cell Carcinoma
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Therapies of Merkel Cell Carcinoma
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Treatment
The diagnosis and therapeutic management of Merkel cell carcinoma requires the coordinated efforts of a team of medical professionals who are focused on diagnosing and treating skin disorders (dermatologists); diagnosing and treating cancer (medical oncologists); cancer treatment through surgery (surgical oncologists); cancer treatment through radiation (radiation oncologists); oncology nurses; dietitians; psychiatrists; and/or other healthcare professionals. Psychosocial support for the entire family is also often indicated because of the rarity and relatively high risk of this cancer.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; location of the tumor; the presence or absence of certain symptoms or tumor histopathologic features; an individual’s age and general health; and/or other factors such as immune health. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.In general, for individuals who have localized disease without involvement of the lymph nodes and without (distant) spread of the cancer, surgery is recommended to remove the primary Merkel cell carcinoma. Usually, the tumor is removed along with some of the healthy skin that surrounds it (wide local excision). If nearby lymph nodes are also affected, but the cancer has not spread (metastasized) further, then the affected lymph nodes are typically treated by surgery and/or radiation treatment. The surgical removal of lymph nodes may be referred to as a lymph node dissection or lymphadenectomyFor some individuals, radiation therapy may be recommended after surgery. This is called adjuvant radiation and is given after primary therapy (in this instance surgery) to help lower the risk that the cancer will come back. The adjuvant radiation therapy means radiotherapy is used to destroy cancerous cells that remain after surgery has removed all clinically detectable tumor (visible tumor). Radiation therapy uses x-rays or similar forms of radiation to directly destroy cancer cells. Radiation therapy can also be used as a primary therapy in people for whom surgical removal of cancer is not possible.Most people with recurrent or metastatic disease are recommended to undergo immunotherapy. This type of treatment aims to enhance the body’s innate ability to fight cancer using the immune system. For example, avelumab is a type of immunotherapy called PD-L1 blockade, which releases the “brakes” on the immune system that some cancers use to try to evade the immune cells.Recent clinical trials of PD-1 or PD-L1 blockade agents (e.g. avelumab, pembrolizumab, and nivolumab) in advanced MCC have demonstrated durable response of approximately 60% for patients who have not been previously treated with chemotherapy. The response rate is approximately 32% for patients who have been previously treated with chemotherapy. Because these immunotherapy responses are very durable (often lasting years), as compared to chemotherapy (typically lasting months), these findings have quickly led to a preference for immunotherapy over chemotherapy for MCC. Based on the data from clinical trials, the U.S. Food and Drug Administration (FDA) approved the immunotherapy, avelumab (Bavencio) in 2017 and pembrolizumab (Keytruda) in 2018 for the treatment of adults and children over the age of 12 who have metastatic Merkel cell carcinoma. Historically, chemotherapy was the preferred systemic treatment option for recurrent or metastatic disease. However, chemotherapy only offers limited benefit with an average period of disease control of approximately 90 days from the start of therapy. There are also concerns about the use of chemotherapy because it typically suppresses activity of the immune system. As a consequence, chemotherapy is no longer recommended as a first-line agent for patients with metastatic MCC who are eligible for immunotherapy. It is generally reserved for patients whose disease does not respond to immunotherapy or for patients with particularly advanced tumors (palliative intent).
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Therapies of Merkel Cell Carcinoma. Treatment
The diagnosis and therapeutic management of Merkel cell carcinoma requires the coordinated efforts of a team of medical professionals who are focused on diagnosing and treating skin disorders (dermatologists); diagnosing and treating cancer (medical oncologists); cancer treatment through surgery (surgical oncologists); cancer treatment through radiation (radiation oncologists); oncology nurses; dietitians; psychiatrists; and/or other healthcare professionals. Psychosocial support for the entire family is also often indicated because of the rarity and relatively high risk of this cancer.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size; location of the tumor; the presence or absence of certain symptoms or tumor histopathologic features; an individual’s age and general health; and/or other factors such as immune health. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.In general, for individuals who have localized disease without involvement of the lymph nodes and without (distant) spread of the cancer, surgery is recommended to remove the primary Merkel cell carcinoma. Usually, the tumor is removed along with some of the healthy skin that surrounds it (wide local excision). If nearby lymph nodes are also affected, but the cancer has not spread (metastasized) further, then the affected lymph nodes are typically treated by surgery and/or radiation treatment. The surgical removal of lymph nodes may be referred to as a lymph node dissection or lymphadenectomyFor some individuals, radiation therapy may be recommended after surgery. This is called adjuvant radiation and is given after primary therapy (in this instance surgery) to help lower the risk that the cancer will come back. The adjuvant radiation therapy means radiotherapy is used to destroy cancerous cells that remain after surgery has removed all clinically detectable tumor (visible tumor). Radiation therapy uses x-rays or similar forms of radiation to directly destroy cancer cells. Radiation therapy can also be used as a primary therapy in people for whom surgical removal of cancer is not possible.Most people with recurrent or metastatic disease are recommended to undergo immunotherapy. This type of treatment aims to enhance the body’s innate ability to fight cancer using the immune system. For example, avelumab is a type of immunotherapy called PD-L1 blockade, which releases the “brakes” on the immune system that some cancers use to try to evade the immune cells.Recent clinical trials of PD-1 or PD-L1 blockade agents (e.g. avelumab, pembrolizumab, and nivolumab) in advanced MCC have demonstrated durable response of approximately 60% for patients who have not been previously treated with chemotherapy. The response rate is approximately 32% for patients who have been previously treated with chemotherapy. Because these immunotherapy responses are very durable (often lasting years), as compared to chemotherapy (typically lasting months), these findings have quickly led to a preference for immunotherapy over chemotherapy for MCC. Based on the data from clinical trials, the U.S. Food and Drug Administration (FDA) approved the immunotherapy, avelumab (Bavencio) in 2017 and pembrolizumab (Keytruda) in 2018 for the treatment of adults and children over the age of 12 who have metastatic Merkel cell carcinoma. Historically, chemotherapy was the preferred systemic treatment option for recurrent or metastatic disease. However, chemotherapy only offers limited benefit with an average period of disease control of approximately 90 days from the start of therapy. There are also concerns about the use of chemotherapy because it typically suppresses activity of the immune system. As a consequence, chemotherapy is no longer recommended as a first-line agent for patients with metastatic MCC who are eligible for immunotherapy. It is generally reserved for patients whose disease does not respond to immunotherapy or for patients with particularly advanced tumors (palliative intent).
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Merkel Cell Carcinoma
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nord_799_0
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Overview of MERRF Syndrome
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SummaryMERRF (myoclonus epilepsy with ragged-red fibers) syndrome is an extremely rare disorder that appears in childhood, adolescence or adulthood after normal development early in life. MERRF syndrome affects the nervous system, skeletal muscles and other body systems. The distinguishing feature in MERRF is muscle jerks (myoclonus), consisting of sudden, brief spasms that can affect the arms, legs or entire body. Individuals with MERRF syndrome may also have seizures (generalized epilepsy), impaired ability to coordinate movements (ataxia), muscle weakness (myopathy), exercise intolerance and a slow decline of intellectual function (dementia). Decreased body height (short stature), vision problems (optic atrophy), hearing loss, heart disease of the heart muscles (cardiomyopathy) and abnormal sensation from nerve damage (peripheral neuropathy) are other common symptoms. Individuals with MERRF syndrome will also have abnormal muscle cells that appear as ragged red fibers (RRF) when stained and viewed microscopically. MERRF syndrome is a mitochondrial disorder. Mitochondria are structures found in the cell that produce energy. Mitochondrial disorders can occur when the mitochondrial genetic material (mtDNA) has a genetic change (mutation) that prevents the mitochondria from carrying out their function. As a result, parts of the body like the brain and muscles may not work properly due to lack of energy. MERRF syndrome is caused by mutations in mtDNA and is inherited from the mother.IntroductionMERRF syndrome was first reported in 1973 when a family was described with muscle jerks (myoclonus), seizures and abnormal muscle cells showing characteristic ragged red fibers (RRF). By 1988, 25 people had been identified with a similar collection of features. That same year it was determined that MERRF syndrome is caused by mutations in mitochondrial DNA, and two years later, in 1990, the first causal genetic mutation was discovered. Today MERRF syndrome is typically diagnosed by a combination of clinical features (myoclonus, seizures, and ataxia) and RRF seen on muscle biopsy. However, not all individuals diagnosed with MERRF syndrome will have, or develop, the same symptoms. A molecular diagnosis of MERRF is made when a genetic mutation is identified in a mitochondrial gene that is known to be associated with the condition. A diagnosis of MERRF syndrome can help guide surveillance, treatment of symptoms and possibly aid in prevention of disease progression. A genetic diagnosis can also clarify risk to siblings, parents, extended family members and biological offspring, and can help in family planning.
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Overview of MERRF Syndrome. SummaryMERRF (myoclonus epilepsy with ragged-red fibers) syndrome is an extremely rare disorder that appears in childhood, adolescence or adulthood after normal development early in life. MERRF syndrome affects the nervous system, skeletal muscles and other body systems. The distinguishing feature in MERRF is muscle jerks (myoclonus), consisting of sudden, brief spasms that can affect the arms, legs or entire body. Individuals with MERRF syndrome may also have seizures (generalized epilepsy), impaired ability to coordinate movements (ataxia), muscle weakness (myopathy), exercise intolerance and a slow decline of intellectual function (dementia). Decreased body height (short stature), vision problems (optic atrophy), hearing loss, heart disease of the heart muscles (cardiomyopathy) and abnormal sensation from nerve damage (peripheral neuropathy) are other common symptoms. Individuals with MERRF syndrome will also have abnormal muscle cells that appear as ragged red fibers (RRF) when stained and viewed microscopically. MERRF syndrome is a mitochondrial disorder. Mitochondria are structures found in the cell that produce energy. Mitochondrial disorders can occur when the mitochondrial genetic material (mtDNA) has a genetic change (mutation) that prevents the mitochondria from carrying out their function. As a result, parts of the body like the brain and muscles may not work properly due to lack of energy. MERRF syndrome is caused by mutations in mtDNA and is inherited from the mother.IntroductionMERRF syndrome was first reported in 1973 when a family was described with muscle jerks (myoclonus), seizures and abnormal muscle cells showing characteristic ragged red fibers (RRF). By 1988, 25 people had been identified with a similar collection of features. That same year it was determined that MERRF syndrome is caused by mutations in mitochondrial DNA, and two years later, in 1990, the first causal genetic mutation was discovered. Today MERRF syndrome is typically diagnosed by a combination of clinical features (myoclonus, seizures, and ataxia) and RRF seen on muscle biopsy. However, not all individuals diagnosed with MERRF syndrome will have, or develop, the same symptoms. A molecular diagnosis of MERRF is made when a genetic mutation is identified in a mitochondrial gene that is known to be associated with the condition. A diagnosis of MERRF syndrome can help guide surveillance, treatment of symptoms and possibly aid in prevention of disease progression. A genetic diagnosis can also clarify risk to siblings, parents, extended family members and biological offspring, and can help in family planning.
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MERRF Syndrome
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Symptoms of MERRF Syndrome
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Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal early development. Signs, symptoms and physical findings associated with MERRF syndrome may vary greatly between affected individuals in the same family and between different families. The age of onset and how quickly the condition progresses can differ between individuals. Brief, sudden, jerking muscle spasms (myoclonus) is usually the first symptom of MERRF syndrome followed by seizures (generalized epilepsy), impaired ability to coordinate movements (ataxia), muscle weakness (myopathy) and exercise intolerance. Decreased body height (short stature), hearing loss, decline of intellectual function (dementia) and altered sensation (pins-and-needles or pain) from nerve damage (peripheral neuropathy) are also common symptoms. Some individuals may have vision problems or vision loss, most commonly caused by degeneration of the optic nerve (optic atrophy). Vision impairment may also result from drooping upper eyelids (ptosis), progressive damage to the receptors that respond to light in the retina of the eye (pigmentary retinopathy) or weakness of the eye muscles (ophthalmoplegia). Heart problems may also arise, including heart disease of the heart muscle (cardiomyopathy) and problems of the heart rhythm (arrhythmia) such as Wolff-Parkinson-White syndrome. Occasionally, people with MERRF syndrome have benign fat cell tumors (lipomas) especially around the neck, too much sugar in the blood (diabetes mellitus) and involuntary muscle stiffness (spasticity) along with other differences in reflexes and movement (pyramidal signs). People with MERRF syndrome frequently have an accumulation of lactic acid in the blood (lactic acidosis) which can cause vomiting, abdominal pain, decreased appetite, unusual sleepiness or fatigue, muscle pain or weakness and difficulty breathing.
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Symptoms of MERRF Syndrome. Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal early development. Signs, symptoms and physical findings associated with MERRF syndrome may vary greatly between affected individuals in the same family and between different families. The age of onset and how quickly the condition progresses can differ between individuals. Brief, sudden, jerking muscle spasms (myoclonus) is usually the first symptom of MERRF syndrome followed by seizures (generalized epilepsy), impaired ability to coordinate movements (ataxia), muscle weakness (myopathy) and exercise intolerance. Decreased body height (short stature), hearing loss, decline of intellectual function (dementia) and altered sensation (pins-and-needles or pain) from nerve damage (peripheral neuropathy) are also common symptoms. Some individuals may have vision problems or vision loss, most commonly caused by degeneration of the optic nerve (optic atrophy). Vision impairment may also result from drooping upper eyelids (ptosis), progressive damage to the receptors that respond to light in the retina of the eye (pigmentary retinopathy) or weakness of the eye muscles (ophthalmoplegia). Heart problems may also arise, including heart disease of the heart muscle (cardiomyopathy) and problems of the heart rhythm (arrhythmia) such as Wolff-Parkinson-White syndrome. Occasionally, people with MERRF syndrome have benign fat cell tumors (lipomas) especially around the neck, too much sugar in the blood (diabetes mellitus) and involuntary muscle stiffness (spasticity) along with other differences in reflexes and movement (pyramidal signs). People with MERRF syndrome frequently have an accumulation of lactic acid in the blood (lactic acidosis) which can cause vomiting, abdominal pain, decreased appetite, unusual sleepiness or fatigue, muscle pain or weakness and difficulty breathing.
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MERRF Syndrome
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Causes of MERRF Syndrome
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MERRF syndrome is caused by genetic changes (mutations) in mitochondrial DNA (mtDNA). Mitochondria, which are found by the hundreds or thousands in the cells of the body, particularly in muscle and nerve tissue, carry the blueprints for regulating energy production. MtDNA encodes specific genes that are the instructions for making some of the essential parts of the mitochondria. MERRF syndrome is caused by mutations in the mtDNA. The genes associated with MERRF syndrome are the instructions for specific molecules called transfer RNAs. Transfer RNAs (tRNAs) help assemble proteins, which then carry out the mitochondrial function of producing energy. Mutations in the mtDNA genes associated with MERRF lead to abnormal tRNAs, and consequently reduce the ability of the mitochondria to build proteins and produce energy for the body. Parts of the body that require a lot of energy, like the muscles and brain, will be the most affected by these mutations.More than 90% of cases of MERRF syndrome are caused by mutations in one mtDNA gene, MT-TK. One specific MT-TK mutation, called m.8344A>G, accounts for 80% of cases. Mutations in MT-TF, MT-TH, MT-TI, MT-TL1, MT-TP, MT-TS1, and MT-TS2 have also been associated with MERRF syndrome. Genes for mitochondria (mtDNA) are inherited from the mother. MtDNA that is found in sperm cells is typically lost during fertilization. As a result, all human mtDNA comes from the mother. A mother with a non-working gene in mtDNA will pass on the non-working gene to all her children, but only her daughters will pass on the non-working gene to their children. As cells divide, the number of normal mtDNA and non-working (mutated) mtDNA are distributed in an unpredictable fashion among different tissues. Consequently, mutated mtDNA accumulates at different rates among different tissues in the same individual. Thus, family members who have the identical non-working gene in mtDNA may exhibit a variety of different symptoms at different times and with varying degrees of severity.Both normal and mutated mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of mitochondria with the non-working gene may be out-numbered by the number of mitochondria without the non-working gene. Symptoms may not appear in any given generation until a significant proportion of mitochondria have mutated mtDNA. The uneven distribution of normal and mutated mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms in affected family members.It is generally thought that a higher number of mutated mtDNA relative to normal mtDNA corresponds with more severe symptoms. However, the number of mutated mtDNA relative to the normal mtDNAs cannot be used to accurately predict if symptoms will present, which symptoms may present or symptom severity.A few rare cases of MERRF syndrome have occurred as the result of a new spontaneous mutation in a mitochondrial gene in the affected individual. These mutations are not inherited, but may be passed down to future generations if the affected individual is female.
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Causes of MERRF Syndrome. MERRF syndrome is caused by genetic changes (mutations) in mitochondrial DNA (mtDNA). Mitochondria, which are found by the hundreds or thousands in the cells of the body, particularly in muscle and nerve tissue, carry the blueprints for regulating energy production. MtDNA encodes specific genes that are the instructions for making some of the essential parts of the mitochondria. MERRF syndrome is caused by mutations in the mtDNA. The genes associated with MERRF syndrome are the instructions for specific molecules called transfer RNAs. Transfer RNAs (tRNAs) help assemble proteins, which then carry out the mitochondrial function of producing energy. Mutations in the mtDNA genes associated with MERRF lead to abnormal tRNAs, and consequently reduce the ability of the mitochondria to build proteins and produce energy for the body. Parts of the body that require a lot of energy, like the muscles and brain, will be the most affected by these mutations.More than 90% of cases of MERRF syndrome are caused by mutations in one mtDNA gene, MT-TK. One specific MT-TK mutation, called m.8344A>G, accounts for 80% of cases. Mutations in MT-TF, MT-TH, MT-TI, MT-TL1, MT-TP, MT-TS1, and MT-TS2 have also been associated with MERRF syndrome. Genes for mitochondria (mtDNA) are inherited from the mother. MtDNA that is found in sperm cells is typically lost during fertilization. As a result, all human mtDNA comes from the mother. A mother with a non-working gene in mtDNA will pass on the non-working gene to all her children, but only her daughters will pass on the non-working gene to their children. As cells divide, the number of normal mtDNA and non-working (mutated) mtDNA are distributed in an unpredictable fashion among different tissues. Consequently, mutated mtDNA accumulates at different rates among different tissues in the same individual. Thus, family members who have the identical non-working gene in mtDNA may exhibit a variety of different symptoms at different times and with varying degrees of severity.Both normal and mutated mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of mitochondria with the non-working gene may be out-numbered by the number of mitochondria without the non-working gene. Symptoms may not appear in any given generation until a significant proportion of mitochondria have mutated mtDNA. The uneven distribution of normal and mutated mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms in affected family members.It is generally thought that a higher number of mutated mtDNA relative to normal mtDNA corresponds with more severe symptoms. However, the number of mutated mtDNA relative to the normal mtDNAs cannot be used to accurately predict if symptoms will present, which symptoms may present or symptom severity.A few rare cases of MERRF syndrome have occurred as the result of a new spontaneous mutation in a mitochondrial gene in the affected individual. These mutations are not inherited, but may be passed down to future generations if the affected individual is female.
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MERRF Syndrome
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Affects of MERRF Syndrome
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MERRF syndrome is a rare disorder that affects males and females in equal numbers. Onset of symptoms of MERRF syndrome can occur in childhood, adolescence or early adulthood. It typically presents after a period of normal early development.The prevalence of MERRF syndrome is unknown. However, several studies of mitochondrial disorders in European populations found that the common MT-TK mutation, m.8344A>G, has a prevalence between 0 and 1.5 per 100,000 adults in northern Finland, 0.39 per 100,000 adults in northern England, between 0 and 0.25 per 100,000 children in western Sweden and 0.7 per 100,000 individuals in northeast England. Consistent with these findings, it is widely considered that the prevalence of MERRF is likely less than 1 per 100,000 individuals. Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MERRF syndrome.
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Affects of MERRF Syndrome. MERRF syndrome is a rare disorder that affects males and females in equal numbers. Onset of symptoms of MERRF syndrome can occur in childhood, adolescence or early adulthood. It typically presents after a period of normal early development.The prevalence of MERRF syndrome is unknown. However, several studies of mitochondrial disorders in European populations found that the common MT-TK mutation, m.8344A>G, has a prevalence between 0 and 1.5 per 100,000 adults in northern Finland, 0.39 per 100,000 adults in northern England, between 0 and 0.25 per 100,000 children in western Sweden and 0.7 per 100,000 individuals in northeast England. Consistent with these findings, it is widely considered that the prevalence of MERRF is likely less than 1 per 100,000 individuals. Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MERRF syndrome.
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MERRF Syndrome
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nord_799_4
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Related disorders of MERRF Syndrome
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MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome is a disorder that begins in childhood and affects mostly the nervous system and muscle. The most common early symptoms are seizures, recurrent headaches, loss of appetite and recurrent vomiting. Stroke-like episodes with temporary muscle weakness on one side of the body (hemiparesis) may also occur and this can lead to altered consciousness, vision and hearing loss, loss of motor skills and intellectual disability. Diabetes mellitus and paralysis of eye muscle (chronic progressive external ophthalmoplegia) are often present in isolation or in association with other symptoms. MELAS is caused by mutations in mitochondrial DNA (mtDNA). Some mutations that cause MELAS are found in mtDNA genes that are also associated with MERRF syndrome. In one patient, this syndrome has been associated with mutations in a nuclear gene, POLG1. (For more information on this disorder, choose “MELAS” as your search term in the Rare Disease Database.)Kearns-Sayre syndrome (KSS) is a rare multisystemic disorder. An important clinical symptomatic feature is the presence of droopy eyelids (ptosis) in one or both eyes. This disease is mostly characterized by three primary findings: progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), or pigmentary retinopathy, leading to poor night vision and progressive vision loss; and heart disease such as cardiomyopathy and/or progressive arrhythmia leading to complete heart block. Other findings may include muscle weakness, short stature, sensorineural hearing loss, endocrine issues such as diabetes mellitus and hypoparathyroidism (which can cause hypocalcemia) and/or the loss of ability to coordinate voluntary movements (ataxia) due to problems affecting part of the brain (cerebellum). In some patients, KSS may be associated with other disorders and/or conditions. KSS belongs (in part) to a group of rare disorders known as mitochondrial encephalomyopathies. Mitochondrial encephalomyopathies are disorders in which a defect in genetic material (DNA) arises from a part of the cell structure (mitochondria), that produces energy (in the form of adenosine triphosphate, or ATP) causing the brain and muscles to function improperly due to lack of energy (encephalomyopathies). In these disorders, abnormally high numbers of defective mitochondria are present. In approximately 80 percent of affected individuals with KSS, tests will reveal missing genetic material (deletion) involving the unique DNA in mitochondria (mtDNA).(For more information on this disorder, choose “Kearns Sayre” as your search term in the Rare Disease Database.)Leigh syndrome is a rare genetic neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and optic nerve). The symptoms of Leigh syndrome usually begin between the ages of three months and two years, but some patients do not exhibit signs and symptoms until several years later. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability and/or seizure activity. As Leigh syndrome progresses, symptoms may also include generalized weakness, lack of muscle tone (hypotonia) and episodes of lactic acidosis, which may lead to impairment of respiratory and kidney function. Several different genetically determined enzyme defects can cause the syndrome, initially described over 60 years ago. Most individuals with Leigh syndrome have defects of mitochondrial energy production, such as deficiency of an enzyme of the mitochondrial respiratory chain complex or the pyruvate dehydrogenase complex. In most patients, Leigh syndrome is inherited in an autosomal recessive pattern. However, X-linked recessive and maternal inheritance, due to a mitochondrial DNA mutation, are seen in some families. (For more information on this disorder, choose “Leigh” as your search term in the Rare Disease Database.)Combined oxidative phosphorylation deficiency is a disease that affects many parts of the body. Onset occurs at or soon after birth in most patients, and features can include growth delay, small head (microcephaly), increased muscle tone, floppiness of the trunk and head, brain disease (encephalopathy), enlarged heart muscle (cardiomyopathy) and liver dysfunction. There are many subtypes, caused by many different gene mutations. Combined oxidative phosphorylation deficiency 27 is characterized by juvenile-onset MERRF-like severe myoclonus epilepsy with ataxia, spastic weakness that affects all four limbs (spastic tetraparesis), vision loss, hearing loss and cognitive decline. It is inherited in an autosomal recessive pattern and is caused by mutations in the CARS2 gene. (For more information on combined oxidative phosphorylation deficiencies, choose “Combined oxidative phosphorylation” as your search term in the Rare Disease Database).POLG-related disorders are a series of conditions with overlapping symptoms. The disorders include: Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), ataxia neuropathy spectrum (ANS), autosomal recessive progressive external ophthalmoplegia (arPEO) and autosomal dominant progressive external ophthalmoplegia (adPEO). Symptoms and severity of these conditions vary but common features include: movement disorder including muscle spasms (myoclonus), seizures (epilepsy), impaired ability to coordinate movements (ataxia), abnormal sensation from nerve damage (peripheral neuropathy), developmental delay, decreased muscle tone (hypotonia) and muscle weakness (myopathy). These disorders are primarily inherited in an autosomal recessive pattern though some do follow an autosomal dominant pattern of inheritance. All are caused by mutations in the POLG gene.
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Related disorders of MERRF Syndrome. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome is a disorder that begins in childhood and affects mostly the nervous system and muscle. The most common early symptoms are seizures, recurrent headaches, loss of appetite and recurrent vomiting. Stroke-like episodes with temporary muscle weakness on one side of the body (hemiparesis) may also occur and this can lead to altered consciousness, vision and hearing loss, loss of motor skills and intellectual disability. Diabetes mellitus and paralysis of eye muscle (chronic progressive external ophthalmoplegia) are often present in isolation or in association with other symptoms. MELAS is caused by mutations in mitochondrial DNA (mtDNA). Some mutations that cause MELAS are found in mtDNA genes that are also associated with MERRF syndrome. In one patient, this syndrome has been associated with mutations in a nuclear gene, POLG1. (For more information on this disorder, choose “MELAS” as your search term in the Rare Disease Database.)Kearns-Sayre syndrome (KSS) is a rare multisystemic disorder. An important clinical symptomatic feature is the presence of droopy eyelids (ptosis) in one or both eyes. This disease is mostly characterized by three primary findings: progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), or pigmentary retinopathy, leading to poor night vision and progressive vision loss; and heart disease such as cardiomyopathy and/or progressive arrhythmia leading to complete heart block. Other findings may include muscle weakness, short stature, sensorineural hearing loss, endocrine issues such as diabetes mellitus and hypoparathyroidism (which can cause hypocalcemia) and/or the loss of ability to coordinate voluntary movements (ataxia) due to problems affecting part of the brain (cerebellum). In some patients, KSS may be associated with other disorders and/or conditions. KSS belongs (in part) to a group of rare disorders known as mitochondrial encephalomyopathies. Mitochondrial encephalomyopathies are disorders in which a defect in genetic material (DNA) arises from a part of the cell structure (mitochondria), that produces energy (in the form of adenosine triphosphate, or ATP) causing the brain and muscles to function improperly due to lack of energy (encephalomyopathies). In these disorders, abnormally high numbers of defective mitochondria are present. In approximately 80 percent of affected individuals with KSS, tests will reveal missing genetic material (deletion) involving the unique DNA in mitochondria (mtDNA).(For more information on this disorder, choose “Kearns Sayre” as your search term in the Rare Disease Database.)Leigh syndrome is a rare genetic neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and optic nerve). The symptoms of Leigh syndrome usually begin between the ages of three months and two years, but some patients do not exhibit signs and symptoms until several years later. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability and/or seizure activity. As Leigh syndrome progresses, symptoms may also include generalized weakness, lack of muscle tone (hypotonia) and episodes of lactic acidosis, which may lead to impairment of respiratory and kidney function. Several different genetically determined enzyme defects can cause the syndrome, initially described over 60 years ago. Most individuals with Leigh syndrome have defects of mitochondrial energy production, such as deficiency of an enzyme of the mitochondrial respiratory chain complex or the pyruvate dehydrogenase complex. In most patients, Leigh syndrome is inherited in an autosomal recessive pattern. However, X-linked recessive and maternal inheritance, due to a mitochondrial DNA mutation, are seen in some families. (For more information on this disorder, choose “Leigh” as your search term in the Rare Disease Database.)Combined oxidative phosphorylation deficiency is a disease that affects many parts of the body. Onset occurs at or soon after birth in most patients, and features can include growth delay, small head (microcephaly), increased muscle tone, floppiness of the trunk and head, brain disease (encephalopathy), enlarged heart muscle (cardiomyopathy) and liver dysfunction. There are many subtypes, caused by many different gene mutations. Combined oxidative phosphorylation deficiency 27 is characterized by juvenile-onset MERRF-like severe myoclonus epilepsy with ataxia, spastic weakness that affects all four limbs (spastic tetraparesis), vision loss, hearing loss and cognitive decline. It is inherited in an autosomal recessive pattern and is caused by mutations in the CARS2 gene. (For more information on combined oxidative phosphorylation deficiencies, choose “Combined oxidative phosphorylation” as your search term in the Rare Disease Database).POLG-related disorders are a series of conditions with overlapping symptoms. The disorders include: Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), ataxia neuropathy spectrum (ANS), autosomal recessive progressive external ophthalmoplegia (arPEO) and autosomal dominant progressive external ophthalmoplegia (adPEO). Symptoms and severity of these conditions vary but common features include: movement disorder including muscle spasms (myoclonus), seizures (epilepsy), impaired ability to coordinate movements (ataxia), abnormal sensation from nerve damage (peripheral neuropathy), developmental delay, decreased muscle tone (hypotonia) and muscle weakness (myopathy). These disorders are primarily inherited in an autosomal recessive pattern though some do follow an autosomal dominant pattern of inheritance. All are caused by mutations in the POLG gene.
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MERRF Syndrome
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nord_799_5
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Diagnosis of MERRF Syndrome
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MERRF syndrome is diagnosed based on clinical findings and molecular genetic testing.A clinical diagnosis of MERRF can be made based on the presence of four features: myoclonus (muscle spasms), generalized epilepsy (seizures), ataxia (impaired ability to coordinate movements) and abnormal muscle cells showing ragged red fibers (RRF) when a muscle biopsy is viewed microscopically.Clinical testing may also reveal other features of MERRF syndrome. Concentrations of lactate and pyruvate are commonly elevated in blood and fluid surrounding the brain and spinal cord (cerebrospinal fluid). Concentrations of lactate and pyruvate may show large increases after moderate physical activity. The concentration of cerebrospinal fluid (CSF) protein may also be elevated in MERRF syndrome. Brain imaging techniques such as magnetic resonance imaging (MRI) may show stroke-like lesions or degeneration of cells (atrophy) and magnetic resonance spectroscopy (MRS) is used to look for lactate in the brain. Electroencephalogram (EEG) measures electrical activity in the brain and can help diagnose seizures. Electrocardiogram (EKG) may be used to diagnose heart rhythm abnormalities. Nerve conduction velocity studies may be consistent with a myopathy or a neuropathy in individuals with MERRF syndrome. A molecular diagnosis of MERRF syndrome is made when an individual who has symptoms consistent with the syndrome is found to have a mutation in a mtDNA gene associated with MERRF. A molecular diagnosis can confirm a clinical diagnosis of MERRF syndrome or help clarify a diagnosis when a clinical diagnosis cannot be made because symptoms overlap with other related disorders. The mtDNA mutations associated with MERRF can usually be detected in white blood cells, but due to heteroplasmy (see Causes), other tissue samples such as skin, saliva, hair follicles, urinary sediment and skeletal muscle, may be necessary to establish a molecular diagnosis.In individuals with a clinical diagnosis or with symptoms that are highly suggestive of MERRF syndrome, molecular genetic testing may begin with a gene-targeted approach. An individual may first be screened for the common mutation, m.8344A>G, in the MT-TK gene. If this mutation is not found, broader genetic testing may be ordered that includes sequencing all genes associated with MERRF syndrome and other genes that cause related disorders (multigene panel testing). Genetic testing in other tissue samples may also be required. In individuals that have general symptoms, such as seizures and muscle weakness that overlap with many other inherited conditions, molecular genetic testing may begin with a very broad approach. In these patients, genetic testing may include sequencing all mtDNA (mitochondrial genome) in addition to all genes (exome sequencing) or all DNA (genome sequencing).Clinical Testing and Work-UpIndividuals with MERRF syndrome and their at-risk relatives should be followed by an interdisciplinary team at regular intervals to monitor any new symptoms and progression of disease. After an initial diagnosis, baseline evaluations recommended include: (1) measurement of height and weight to detect short stature, (2) neurologic evaluation with a head MRI, MRS, EEG and neuropsychiatric testing to detect differences in the brain, presence of seizures and evidence of dementia, (3) hearing (audiologic) evaluation to detect hearing impairment, (4) eye (ophthalmologic) evaluation to detect vision problems, (5) physical and occupational therapy assessments, (6) cardiac evaluation with a EKG and echocardiogram to detect heart abnormalities, and (7) fasting serum glucose and glucose tolerance test to detect diabetes mellitus. Genetic counseling is recommended for affected individuals and their families.
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Diagnosis of MERRF Syndrome. MERRF syndrome is diagnosed based on clinical findings and molecular genetic testing.A clinical diagnosis of MERRF can be made based on the presence of four features: myoclonus (muscle spasms), generalized epilepsy (seizures), ataxia (impaired ability to coordinate movements) and abnormal muscle cells showing ragged red fibers (RRF) when a muscle biopsy is viewed microscopically.Clinical testing may also reveal other features of MERRF syndrome. Concentrations of lactate and pyruvate are commonly elevated in blood and fluid surrounding the brain and spinal cord (cerebrospinal fluid). Concentrations of lactate and pyruvate may show large increases after moderate physical activity. The concentration of cerebrospinal fluid (CSF) protein may also be elevated in MERRF syndrome. Brain imaging techniques such as magnetic resonance imaging (MRI) may show stroke-like lesions or degeneration of cells (atrophy) and magnetic resonance spectroscopy (MRS) is used to look for lactate in the brain. Electroencephalogram (EEG) measures electrical activity in the brain and can help diagnose seizures. Electrocardiogram (EKG) may be used to diagnose heart rhythm abnormalities. Nerve conduction velocity studies may be consistent with a myopathy or a neuropathy in individuals with MERRF syndrome. A molecular diagnosis of MERRF syndrome is made when an individual who has symptoms consistent with the syndrome is found to have a mutation in a mtDNA gene associated with MERRF. A molecular diagnosis can confirm a clinical diagnosis of MERRF syndrome or help clarify a diagnosis when a clinical diagnosis cannot be made because symptoms overlap with other related disorders. The mtDNA mutations associated with MERRF can usually be detected in white blood cells, but due to heteroplasmy (see Causes), other tissue samples such as skin, saliva, hair follicles, urinary sediment and skeletal muscle, may be necessary to establish a molecular diagnosis.In individuals with a clinical diagnosis or with symptoms that are highly suggestive of MERRF syndrome, molecular genetic testing may begin with a gene-targeted approach. An individual may first be screened for the common mutation, m.8344A>G, in the MT-TK gene. If this mutation is not found, broader genetic testing may be ordered that includes sequencing all genes associated with MERRF syndrome and other genes that cause related disorders (multigene panel testing). Genetic testing in other tissue samples may also be required. In individuals that have general symptoms, such as seizures and muscle weakness that overlap with many other inherited conditions, molecular genetic testing may begin with a very broad approach. In these patients, genetic testing may include sequencing all mtDNA (mitochondrial genome) in addition to all genes (exome sequencing) or all DNA (genome sequencing).Clinical Testing and Work-UpIndividuals with MERRF syndrome and their at-risk relatives should be followed by an interdisciplinary team at regular intervals to monitor any new symptoms and progression of disease. After an initial diagnosis, baseline evaluations recommended include: (1) measurement of height and weight to detect short stature, (2) neurologic evaluation with a head MRI, MRS, EEG and neuropsychiatric testing to detect differences in the brain, presence of seizures and evidence of dementia, (3) hearing (audiologic) evaluation to detect hearing impairment, (4) eye (ophthalmologic) evaluation to detect vision problems, (5) physical and occupational therapy assessments, (6) cardiac evaluation with a EKG and echocardiogram to detect heart abnormalities, and (7) fasting serum glucose and glucose tolerance test to detect diabetes mellitus. Genetic counseling is recommended for affected individuals and their families.
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MERRF Syndrome
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Therapies of MERRF Syndrome
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TreatmentNo specific treatment is available for MERRF syndrome. Some medications and therapies may be helpful in managing symptoms.Traditional anticonvulsant drugs are used to help prevent and control seizures associated with MERRF syndrome. Valproic acid should be avoided in the treatment of seizures. Levetiracetam and clonazepam have been effective in controlling myoclonus in a small number of patients. Standard treatment for heart problems (cardiomyopathies and arrhythmias) can be used per cardiologist recommendation. Hearing aids and cochlear implants can improve hearing impairments. Physical therapy, occupational therapy and aerobic exercise may help to improve muscle weakness, stiffness, and motor function.Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme Q10 (CoQ10) and L-carnitine have been beneficial in some patients with different mitochondrial diseases. Additionally, supplements such as ubiquinol, carnitine, alpha lipoic acid, vitamin E, vitamin B complex and creatine may be of benefit to some individuals with mitochondrial disease with muscle involvement. Efficacy of these supplements is being studied in clinical trials. Individuals with MERRF should avoid mitochondrial toxins such as aminoglycoside antibiotics, linezolid, cigarettes and alcohol.
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Therapies of MERRF Syndrome. TreatmentNo specific treatment is available for MERRF syndrome. Some medications and therapies may be helpful in managing symptoms.Traditional anticonvulsant drugs are used to help prevent and control seizures associated with MERRF syndrome. Valproic acid should be avoided in the treatment of seizures. Levetiracetam and clonazepam have been effective in controlling myoclonus in a small number of patients. Standard treatment for heart problems (cardiomyopathies and arrhythmias) can be used per cardiologist recommendation. Hearing aids and cochlear implants can improve hearing impairments. Physical therapy, occupational therapy and aerobic exercise may help to improve muscle weakness, stiffness, and motor function.Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme Q10 (CoQ10) and L-carnitine have been beneficial in some patients with different mitochondrial diseases. Additionally, supplements such as ubiquinol, carnitine, alpha lipoic acid, vitamin E, vitamin B complex and creatine may be of benefit to some individuals with mitochondrial disease with muscle involvement. Efficacy of these supplements is being studied in clinical trials. Individuals with MERRF should avoid mitochondrial toxins such as aminoglycoside antibiotics, linezolid, cigarettes and alcohol.
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MERRF Syndrome
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