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Causes of Tolosa Hunt Syndrome
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While the exact cause of Tolosa-Hunt syndrome is unknown, one theory is an abnormal autoimmune response linked with an inflammation in a specific area behind the eye (cavernous sinus and superior orbital fissure). In some cases, inflammation may be due to a clumping of a certain type of cell (granulomatous inflammation). Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. Other possible causes may include generalized inflammation and constricted or inflamed cranial blood vessels.
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Causes of Tolosa Hunt Syndrome. While the exact cause of Tolosa-Hunt syndrome is unknown, one theory is an abnormal autoimmune response linked with an inflammation in a specific area behind the eye (cavernous sinus and superior orbital fissure). In some cases, inflammation may be due to a clumping of a certain type of cell (granulomatous inflammation). Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. Other possible causes may include generalized inflammation and constricted or inflamed cranial blood vessels.
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Tolosa Hunt Syndrome
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Affects of Tolosa Hunt Syndrome
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Tolosa-Hunt syndrome is a rare neuro-immunological disorder that occurs in males and females in equal numbers. The average age of onset is 41 years, but there have been cases reported among people younger than age 30. In rare cases, children under the age of 10 have been diagnosed with Tolosa-Hunt syndrome.
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Affects of Tolosa Hunt Syndrome. Tolosa-Hunt syndrome is a rare neuro-immunological disorder that occurs in males and females in equal numbers. The average age of onset is 41 years, but there have been cases reported among people younger than age 30. In rare cases, children under the age of 10 have been diagnosed with Tolosa-Hunt syndrome.
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Tolosa Hunt Syndrome
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Related disorders of Tolosa Hunt Syndrome
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Symptoms of the following disorders can be similar to those of Tolosa-Hunt syndrome. Comparisons may be useful for differential diagnosis:Orbital cellulitis is characterized by inflammation of the tissues within the cavity which holds the eyeball. Symptoms include extreme pain, impaired eye movement, swelling, fever and a general feeling of discomfort. Possible complications may include impaired vision, vein abnormalities and spread of the inflammation to the entire orbit, brain or the membranes surrounding the brain.Cavernous sinus thrombosis is an ophthalmologic disorder usually caused by infection and clotting in veins behind the eyeball. It can be a complication of Orbital Cellulitis or infections of facial skin. Swelling and protrusion of both eyes, fever, headache, poor eye movements, droopy eyelids, facial numbness, and an overly sick appearing patient are symptoms of this deadly disorder. Prompt treatment with antibiotics and blood thinners and rest is recommended.Migraine headaches usually involve one side of the head like the Tolosa-Hunt syndrome. Individuals who suffer from these intense headaches may have a genetic predisposition to them. Often associated with these painful attacks are irritability, nausea, vomiting, constipation or diarrhea, and sensitivity to light. Medical researchers believe constriction of the cranial arteries may precede migraine headaches in some cases. Poor eye movements are not characteristic of migraine headaches and should alert physicians to the possibility of Tolosa-Hunt syndrome.
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Related disorders of Tolosa Hunt Syndrome. Symptoms of the following disorders can be similar to those of Tolosa-Hunt syndrome. Comparisons may be useful for differential diagnosis:Orbital cellulitis is characterized by inflammation of the tissues within the cavity which holds the eyeball. Symptoms include extreme pain, impaired eye movement, swelling, fever and a general feeling of discomfort. Possible complications may include impaired vision, vein abnormalities and spread of the inflammation to the entire orbit, brain or the membranes surrounding the brain.Cavernous sinus thrombosis is an ophthalmologic disorder usually caused by infection and clotting in veins behind the eyeball. It can be a complication of Orbital Cellulitis or infections of facial skin. Swelling and protrusion of both eyes, fever, headache, poor eye movements, droopy eyelids, facial numbness, and an overly sick appearing patient are symptoms of this deadly disorder. Prompt treatment with antibiotics and blood thinners and rest is recommended.Migraine headaches usually involve one side of the head like the Tolosa-Hunt syndrome. Individuals who suffer from these intense headaches may have a genetic predisposition to them. Often associated with these painful attacks are irritability, nausea, vomiting, constipation or diarrhea, and sensitivity to light. Medical researchers believe constriction of the cranial arteries may precede migraine headaches in some cases. Poor eye movements are not characteristic of migraine headaches and should alert physicians to the possibility of Tolosa-Hunt syndrome.
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Tolosa Hunt Syndrome
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Diagnosis of Tolosa Hunt Syndrome
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The diagnosis of Tolosa-Hunt syndrome has been codified by the International Headache Society. The following criteria must be met for a definitive diagnosis of this disorder: Eye pain on one side of the head that persists for at least eight weeks if untreated; associated irritation or damage to the third, fourth, or sixth cranial nerves; relief of pain within 48 hours upon the administration of steroids; and specialized testing that rules out other conditions such as neoplasm, infection or aneurysm.The diagnosis of Tolosa-Hunt syndrome is suspected based upon the presence of characteristic physical features (e.g., pain, headache, ophthalmoplegia). The diagnosis may be confirmed by a thorough clinical evaluation, detailed patient history, and a variety of specialized radiologic tests including computed tomography (CT) scan, and magnetic resonance imaging (MRI). These examinations may reveal characteristic enlargement or inflammation of the areas behind the eye (cavernous sinus and superior orbital fissure).
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Diagnosis of Tolosa Hunt Syndrome. The diagnosis of Tolosa-Hunt syndrome has been codified by the International Headache Society. The following criteria must be met for a definitive diagnosis of this disorder: Eye pain on one side of the head that persists for at least eight weeks if untreated; associated irritation or damage to the third, fourth, or sixth cranial nerves; relief of pain within 48 hours upon the administration of steroids; and specialized testing that rules out other conditions such as neoplasm, infection or aneurysm.The diagnosis of Tolosa-Hunt syndrome is suspected based upon the presence of characteristic physical features (e.g., pain, headache, ophthalmoplegia). The diagnosis may be confirmed by a thorough clinical evaluation, detailed patient history, and a variety of specialized radiologic tests including computed tomography (CT) scan, and magnetic resonance imaging (MRI). These examinations may reveal characteristic enlargement or inflammation of the areas behind the eye (cavernous sinus and superior orbital fissure).
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Tolosa Hunt Syndrome
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Therapies of Tolosa Hunt Syndrome
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Treatment
In most cases, the pain associated with Tolosa-Hunt syndrome subsides with short-term use of steroid drugs. Pain is usually reduced in untreated cases within fifteen to twenty days. With steroid treatment, pain typically briskly subsides within twenty-four to seventy-two hours – and this brisk steroid response aids in the diagnosis. Affected individuals may be vulnerable to recurrent future attacks.
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Therapies of Tolosa Hunt Syndrome. Treatment
In most cases, the pain associated with Tolosa-Hunt syndrome subsides with short-term use of steroid drugs. Pain is usually reduced in untreated cases within fifteen to twenty days. With steroid treatment, pain typically briskly subsides within twenty-four to seventy-two hours – and this brisk steroid response aids in the diagnosis. Affected individuals may be vulnerable to recurrent future attacks.
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Tolosa Hunt Syndrome
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nord_1215_0
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Overview of Tongue Cancer
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Tongue cancers are oral cancers that are differentiated by their location in the mouth and on the tongue. If the cancer is on the forward portion of the tongue, it is known as a squamous cell cancer of the oral tongue. If the cancer is located towards the rear third of the tongue, it is known as a squamous cell cancer at the base of the tongue.The characteristics of these two cancers are quite distinct, and reflect the differences in their origins. The difference in origins is also the reason that the treatment of these two forms of tongue cancer is quite different. Oral cancers are relatively rare, representing only about three percent of all cancers.
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Overview of Tongue Cancer. Tongue cancers are oral cancers that are differentiated by their location in the mouth and on the tongue. If the cancer is on the forward portion of the tongue, it is known as a squamous cell cancer of the oral tongue. If the cancer is located towards the rear third of the tongue, it is known as a squamous cell cancer at the base of the tongue.The characteristics of these two cancers are quite distinct, and reflect the differences in their origins. The difference in origins is also the reason that the treatment of these two forms of tongue cancer is quite different. Oral cancers are relatively rare, representing only about three percent of all cancers.
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Tongue Cancer
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Symptoms of Tongue Cancer
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Generally, the first sign of squamous cell cancer of the oral tongue is a pinkish-red sore at the side of the tongue that persists and seems not to heal over time. Quite often, the sore bleeds easily if bitten or touched. If this occurs, it is recommended that the person see a physician, especially if the person is older than fifty.In its earliest developmental period, squamous cell cancer of the base of the tongue is asymptomatic. This means that the cancer does not make itself known until later in its growth. However, symptoms may begin with pain in the tongue and surrounding tissue, changes in voice tones and sounds, and difficulty in swallowing that may lead to feelings of bloat or fullness. Because the early symptoms are dormant, most squamous cell cancers of the base of the tongue are further advanced by the time a patient sees a physician. Many patients will have already had squamous cancer cells in the lymph nodes of the neck (metastases).
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Symptoms of Tongue Cancer. Generally, the first sign of squamous cell cancer of the oral tongue is a pinkish-red sore at the side of the tongue that persists and seems not to heal over time. Quite often, the sore bleeds easily if bitten or touched. If this occurs, it is recommended that the person see a physician, especially if the person is older than fifty.In its earliest developmental period, squamous cell cancer of the base of the tongue is asymptomatic. This means that the cancer does not make itself known until later in its growth. However, symptoms may begin with pain in the tongue and surrounding tissue, changes in voice tones and sounds, and difficulty in swallowing that may lead to feelings of bloat or fullness. Because the early symptoms are dormant, most squamous cell cancers of the base of the tongue are further advanced by the time a patient sees a physician. Many patients will have already had squamous cancer cells in the lymph nodes of the neck (metastases).
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Causes of Tongue Cancer
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The cause of tongue cancer is unknown. Inadequate oral hygiene and thickened white patches on the mucous membranes of the oral cavity (leukoplakia) may be a cause. The disorder is statistically linked with alcoholism, cirrhosis of the liver, excessive smoking, and syphilis.Irritation by jagged teeth, projecting fillings and ill-fitting dentures may also be factors contributing to development of tongue cancer. As in some other types of cancer, the possibility of a genetic predisposition to malignancy may also be a factor.
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Causes of Tongue Cancer. The cause of tongue cancer is unknown. Inadequate oral hygiene and thickened white patches on the mucous membranes of the oral cavity (leukoplakia) may be a cause. The disorder is statistically linked with alcoholism, cirrhosis of the liver, excessive smoking, and syphilis.Irritation by jagged teeth, projecting fillings and ill-fitting dentures may also be factors contributing to development of tongue cancer. As in some other types of cancer, the possibility of a genetic predisposition to malignancy may also be a factor.
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Tongue Cancer
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Affects of Tongue Cancer
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Tongue cancer is most common in men over age 60. It is rare in people, particularly women, under age 40.
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Affects of Tongue Cancer. Tongue cancer is most common in men over age 60. It is rare in people, particularly women, under age 40.
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Tongue Cancer
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Related disorders of Tongue Cancer
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There are many types of mouth cancer. All types are relatively rare.Carcinoma of the floor of the mouth is characterized by a hard growth that can be felt by the tip of the tongue. Pain in the ear, increased salivation, difficulty speaking and later bleeding, are signs of this disorder. This type of cancer may be caused by poor oral hygiene or irritation of the tissues by sharp teeth, ill-fitting dentures, smoking, etc. Frequently, the lymph nodes in the neck are also affected.Carcinoma of the cheek (mouth, buccal mucosa, carcinoma) is characterized by a malignant lesion in the cheek, pain, difficulty chewing, spasms in the cheek muscles (trismus) and mucosal bleeding. The carcinoma may spread to the lymph glands under the jaw.
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Related disorders of Tongue Cancer. There are many types of mouth cancer. All types are relatively rare.Carcinoma of the floor of the mouth is characterized by a hard growth that can be felt by the tip of the tongue. Pain in the ear, increased salivation, difficulty speaking and later bleeding, are signs of this disorder. This type of cancer may be caused by poor oral hygiene or irritation of the tissues by sharp teeth, ill-fitting dentures, smoking, etc. Frequently, the lymph nodes in the neck are also affected.Carcinoma of the cheek (mouth, buccal mucosa, carcinoma) is characterized by a malignant lesion in the cheek, pain, difficulty chewing, spasms in the cheek muscles (trismus) and mucosal bleeding. The carcinoma may spread to the lymph glands under the jaw.
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Tongue Cancer
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Diagnosis of Tongue Cancer
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Examination of a sample of tissue from the site of the suspected cancer by a qualified pathologist is the key to diagnosis. MRI and/or CAT scans may be ordered to determine the location and size of the growth. This examination will also determine the stage of the disorder (how advanced it may be), which in turn, will help determine the method and pace of treatment.
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Diagnosis of Tongue Cancer. Examination of a sample of tissue from the site of the suspected cancer by a qualified pathologist is the key to diagnosis. MRI and/or CAT scans may be ordered to determine the location and size of the growth. This examination will also determine the stage of the disorder (how advanced it may be), which in turn, will help determine the method and pace of treatment.
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Tongue Cancer
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Therapies of Tongue Cancer
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TreatmentNot all specialists agree on the form of treatment of an oral tumor at any particular stage. Most do, however, agree that any dental work that the patient may need should be taken care of before treatment of the cancer begins and that smoking must stop. Treatment usually consists of surgery followed by radiation therapy. Chemotherapy is less commonly administered.Controversy exists among cancer specialists (oncologists) and among head & neck surgeons regarding which of several surgical procedures yields better outcomes. Controversy also exists regarding the used of implanted radioactive seeds (brachytherapy) as an alternative to external beam therapy. Regardless, early diagnosis and treatment is imperative, especially in individuals under 20 years of age.
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Therapies of Tongue Cancer. TreatmentNot all specialists agree on the form of treatment of an oral tumor at any particular stage. Most do, however, agree that any dental work that the patient may need should be taken care of before treatment of the cancer begins and that smoking must stop. Treatment usually consists of surgery followed by radiation therapy. Chemotherapy is less commonly administered.Controversy exists among cancer specialists (oncologists) and among head & neck surgeons regarding which of several surgical procedures yields better outcomes. Controversy also exists regarding the used of implanted radioactive seeds (brachytherapy) as an alternative to external beam therapy. Regardless, early diagnosis and treatment is imperative, especially in individuals under 20 years of age.
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Overview of Tongue, Hairy
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Hairy tongue is an uncommon, benign condition that is also known as black hairy tongue or lingua nigra. It is characterized by abnormal elongation and blackish or dark brownish discoloration or “staining” of the thread-like elevations (filiform papillae) that cover most of the tongue's surface (dorsum linguae). Such changes often begin at the back (posterior) region of the top of the tongue and extend toward the front (anterior) of the tongue's surface but never involve the undersurface.The specific underlying cause of hairy tongue is unknown. However, possible predisposing factors may include poor oral hygiene and overgrowth of pigment-producing bacteria or fungi in the mouth, treatment with certain antibiotic medications, smoking, chewing tobacco, and/or mouthwash use.
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Overview of Tongue, Hairy. Hairy tongue is an uncommon, benign condition that is also known as black hairy tongue or lingua nigra. It is characterized by abnormal elongation and blackish or dark brownish discoloration or “staining” of the thread-like elevations (filiform papillae) that cover most of the tongue's surface (dorsum linguae). Such changes often begin at the back (posterior) region of the top of the tongue and extend toward the front (anterior) of the tongue's surface but never involve the undersurface.The specific underlying cause of hairy tongue is unknown. However, possible predisposing factors may include poor oral hygiene and overgrowth of pigment-producing bacteria or fungi in the mouth, treatment with certain antibiotic medications, smoking, chewing tobacco, and/or mouthwash use.
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Symptoms of Tongue, Hairy
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Hairy tongue is characterized by elongation and overgrowth (hyperplasia) of the filiform papillae into “hair-like” projections and the development of a dark brown or black coating on the surface of the tongue. Such changes typically occur in a triangular region in front of the circumvallate papillae, which are the largest papillae of the tongue. (These nodular elevations, which typically range from eight to 12 in number, are arranged in the form of a “V”.) As noted above, the back region of the top of the tongue may initially be affected with subsequent extension toward the front.Many individuals with hairy tongue have no associated symptoms (asymptomatic). However, some with the condition may be affected by nausea, gagging, altered taste, bad breath (halitosis), and/or other associated symptoms.In some cases, hairy tongue may spontaneously disappear. In addition, it typically subsides with appropriate oral hygiene and the elimination of other predisposing factors. (For more information, please see the “Standard Therapies” section below.)
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Symptoms of Tongue, Hairy. Hairy tongue is characterized by elongation and overgrowth (hyperplasia) of the filiform papillae into “hair-like” projections and the development of a dark brown or black coating on the surface of the tongue. Such changes typically occur in a triangular region in front of the circumvallate papillae, which are the largest papillae of the tongue. (These nodular elevations, which typically range from eight to 12 in number, are arranged in the form of a “V”.) As noted above, the back region of the top of the tongue may initially be affected with subsequent extension toward the front.Many individuals with hairy tongue have no associated symptoms (asymptomatic). However, some with the condition may be affected by nausea, gagging, altered taste, bad breath (halitosis), and/or other associated symptoms.In some cases, hairy tongue may spontaneously disappear. In addition, it typically subsides with appropriate oral hygiene and the elimination of other predisposing factors. (For more information, please see the “Standard Therapies” section below.)
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Causes of Tongue, Hairy
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Hairy tongue is thought to result from failure of the normal “shedding” (desquamation) of the outermost layer of the filiform papillae, overgrowth of certain pigment-producing bacteria or fungi normally present in the mouth, and an abnormal accumulation of pigment residues, keratin, or other debris in the region. (Keratin is a fibrous protein that is a primary component of the outermost layer of the skin, nails, and hair.) Although the specific underlying cause of hairy tongue remains unknown, several potential predisposing factors have been implicated. Such factors include treatment with certain antibiotic medications (e.g., tetracycline therapy, which may lead to overgrowth of certain fungi); the use of particular oral bismuth-containing medications; the use of mouthwashes; smoking; chewing tobacco; excessive alcohol consumption; and/or poor oral hygiene. Hairy tongue is not infectious nor does it lead to oral cancer.
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Causes of Tongue, Hairy. Hairy tongue is thought to result from failure of the normal “shedding” (desquamation) of the outermost layer of the filiform papillae, overgrowth of certain pigment-producing bacteria or fungi normally present in the mouth, and an abnormal accumulation of pigment residues, keratin, or other debris in the region. (Keratin is a fibrous protein that is a primary component of the outermost layer of the skin, nails, and hair.) Although the specific underlying cause of hairy tongue remains unknown, several potential predisposing factors have been implicated. Such factors include treatment with certain antibiotic medications (e.g., tetracycline therapy, which may lead to overgrowth of certain fungi); the use of particular oral bismuth-containing medications; the use of mouthwashes; smoking; chewing tobacco; excessive alcohol consumption; and/or poor oral hygiene. Hairy tongue is not infectious nor does it lead to oral cancer.
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Affects of Tongue, Hairy
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In males or females with hairy tongue, the age of onset is variable. Hairy tongue most commonly affects adults; however, it may sometimes occur during childhood or adolescence. It is not an inherited disease.
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Affects of Tongue, Hairy. In males or females with hairy tongue, the age of onset is variable. Hairy tongue most commonly affects adults; however, it may sometimes occur during childhood or adolescence. It is not an inherited disease.
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Tongue, Hairy
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Related disorders of Tongue, Hairy
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There are additional disorders and conditions that may result in abnormal color changes or other alterations of the tongue. Such conditions and disorders are typically characterized by symptoms and physical findings that differ from those associated with hairy tongue. (For further information, choose the specific condition name in question as your search term in the Rare Disease Database.)
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Related disorders of Tongue, Hairy. There are additional disorders and conditions that may result in abnormal color changes or other alterations of the tongue. Such conditions and disorders are typically characterized by symptoms and physical findings that differ from those associated with hairy tongue. (For further information, choose the specific condition name in question as your search term in the Rare Disease Database.)
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Tongue, Hairy
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Diagnosis of Tongue, Hairy
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Diagnosis of Tongue, Hairy.
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Tongue, Hairy
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Therapies of Tongue, Hairy
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In individuals with suspected hairy tongue, receiving a thorough evaluation by physicians, dentists, and/or oral surgeons is important to exclude other underlying conditions and to confirm a diagnosis of hairy tongue. Recommended treatment measures typically include removing potential predisposing factors, such as stopping smoking, discontinuing antibiotic therapy if possible and receiving proper alternative treatments as necessary under a physician's direction, and/or other appropriate steps. In addition, affected individuals should speak with their dental specialists for guidance concerning appropriate measures to improve oral hygiene in their particular case. Such measures typically include using a soft-bristled toothbrush to regularly cleanse the tongue.
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Therapies of Tongue, Hairy. In individuals with suspected hairy tongue, receiving a thorough evaluation by physicians, dentists, and/or oral surgeons is important to exclude other underlying conditions and to confirm a diagnosis of hairy tongue. Recommended treatment measures typically include removing potential predisposing factors, such as stopping smoking, discontinuing antibiotic therapy if possible and receiving proper alternative treatments as necessary under a physician's direction, and/or other appropriate steps. In addition, affected individuals should speak with their dental specialists for guidance concerning appropriate measures to improve oral hygiene in their particular case. Such measures typically include using a soft-bristled toothbrush to regularly cleanse the tongue.
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Tongue, Hairy
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nord_1217_0
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Overview of Tooth Agenesis
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Tooth agenesis is a condition in which teeth are missing. Anodontia is a genetic disorder defined as the absence of all teeth. It usually occurs as part of a syndrome that includes other abnormalities. Also rare but more common than anodontia are hypodontia and oligodontia. Hypodontia is genetic in origin and usually involves the absence of from 1 to 5 teeth. Oligodontia is genetic as well and is the term used to describe a condition in which six or more teeth are missing.Hypodontia/oligodontia/anodontia might be considered as a unique clinical entity but with increasing severity.These conditions may involve either the primary or permanent sets of teeth, but most cases involve the permanent teeth. Tooth agenesis occurs following a specific pattern of missing teeth. Not only the number of missing teeth, but also the type of missing teeth, must be considered.Tooth agenesis is often associated with a group of conditions affecting the development or function of the teeth, hair, nails and sweat glands called ectodermal dysplasias.
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Overview of Tooth Agenesis. Tooth agenesis is a condition in which teeth are missing. Anodontia is a genetic disorder defined as the absence of all teeth. It usually occurs as part of a syndrome that includes other abnormalities. Also rare but more common than anodontia are hypodontia and oligodontia. Hypodontia is genetic in origin and usually involves the absence of from 1 to 5 teeth. Oligodontia is genetic as well and is the term used to describe a condition in which six or more teeth are missing.Hypodontia/oligodontia/anodontia might be considered as a unique clinical entity but with increasing severity.These conditions may involve either the primary or permanent sets of teeth, but most cases involve the permanent teeth. Tooth agenesis occurs following a specific pattern of missing teeth. Not only the number of missing teeth, but also the type of missing teeth, must be considered.Tooth agenesis is often associated with a group of conditions affecting the development or function of the teeth, hair, nails and sweat glands called ectodermal dysplasias.
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Tooth Agenesis
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Symptoms of Tooth Agenesis
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Hypo/oligodontia is characterized by partial and anodontia by complete absence of teeth. Since all primary teeth are usually present by the age of three, their absence is usually noted, and a dentist consulted. Except for wisdom teeth, all permanent teeth are usually present by the ages 12 to 14. When teeth have not appeared by the appropriate age, dental panoramic X-rays are usually taken.When hypo/oligodontia and surely anodontia occur, abnormalities of hair, nails, and sweat glands may also be present. In many cases, hypo/oligodontia is a component of one of the ectodermal dysplasias, a group of hereditary disorders.
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Symptoms of Tooth Agenesis. Hypo/oligodontia is characterized by partial and anodontia by complete absence of teeth. Since all primary teeth are usually present by the age of three, their absence is usually noted, and a dentist consulted. Except for wisdom teeth, all permanent teeth are usually present by the ages 12 to 14. When teeth have not appeared by the appropriate age, dental panoramic X-rays are usually taken.When hypo/oligodontia and surely anodontia occur, abnormalities of hair, nails, and sweat glands may also be present. In many cases, hypo/oligodontia is a component of one of the ectodermal dysplasias, a group of hereditary disorders.
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Causes of Tooth Agenesis
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Several different genes have been found to be associated with hypo/oligodontia and anodontia including the EDA, EDAR and EDARADD genes.The same genes are involved in so called isolated hypo/oligodontia (only missing teeth) or associated hypo/oligodontia with other symptoms in syndromes like ectodermal dysplasias. EDA, EDAR and EDARADD genes are indeed responsible for isolated or syndromic hypo/oligodontia.Many other genes are involved in hypo/oligodontia such as MSX1, PAX9, IRF6, GREM2, AXIN2, LRP6, SMOC2, LTBP3, PITX2, TSPEAR and WNT10B. WNT10A is now recognized as being the major gene involved in the etiology of hypodontia/oligodontia.Many genes have been associated to isolated and/or syndromic hypo/oligodontia: ADAMTS2, ANOS1, ANTXR1, ATP6V1B2, AXIN2, BCOR, BLM, BMP2, BMP4, CDH3, COL17A1, COL1A1, COL1A2, COL3A1, CREB3L1, CREBBP, CTNNB1, CXORF5, DKK1, DSP, DTDST, EDA, EDAR, EDARADD, ETV6, EVC1, EVC2, EYA1, FAM20A, FGF10, FGFR1, FGFR2, FGFR3, FLNB, FOXC1, GJA1, GJB6, GLI3, GREM2, GRHL2, GRHL3, HOXB1, HRAS, IFT122, IFT43, IKBKG, IKKγ, IRF6, JAG1, KCTD1, KDF1, KDM6A, KMT2D,KREMEN1, LAMA3, LAMB3, LEF1, LRP4, LRP6, LTBP3, MEGF8, MKKS, MSX1, NECTIN4=PVRL4, NSD1, OFD1, P63, PAX3, PAX9, PHGDH, PITX2, PKP1, POC1A, POLR1D, POLR1C, POLR3A, POLR3B, POLR3GL, PORCN, PROK2, PROKR2, PVRL1, PVR4, RAB23, RECQL4, RNF216, RPS6KA3, RSK2, RUNX2, SATB2, SHH, SLC26A2, SLC29A3, SMOC2, SPECC1L, TBCE, TBX3, TBX22, TCOF1, TFAP2B, TP63, TSPEAR, UBR1, WDR19, WDR35, WNT10A, WNT10B.Depending on the gene involved, inheritance can follow different modes of inheritance. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.In some individuals, the disorder is due to a spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.
X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly 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. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working gene he will develop the disease.Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.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.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.
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Causes of Tooth Agenesis. Several different genes have been found to be associated with hypo/oligodontia and anodontia including the EDA, EDAR and EDARADD genes.The same genes are involved in so called isolated hypo/oligodontia (only missing teeth) or associated hypo/oligodontia with other symptoms in syndromes like ectodermal dysplasias. EDA, EDAR and EDARADD genes are indeed responsible for isolated or syndromic hypo/oligodontia.Many other genes are involved in hypo/oligodontia such as MSX1, PAX9, IRF6, GREM2, AXIN2, LRP6, SMOC2, LTBP3, PITX2, TSPEAR and WNT10B. WNT10A is now recognized as being the major gene involved in the etiology of hypodontia/oligodontia.Many genes have been associated to isolated and/or syndromic hypo/oligodontia: ADAMTS2, ANOS1, ANTXR1, ATP6V1B2, AXIN2, BCOR, BLM, BMP2, BMP4, CDH3, COL17A1, COL1A1, COL1A2, COL3A1, CREB3L1, CREBBP, CTNNB1, CXORF5, DKK1, DSP, DTDST, EDA, EDAR, EDARADD, ETV6, EVC1, EVC2, EYA1, FAM20A, FGF10, FGFR1, FGFR2, FGFR3, FLNB, FOXC1, GJA1, GJB6, GLI3, GREM2, GRHL2, GRHL3, HOXB1, HRAS, IFT122, IFT43, IKBKG, IKKγ, IRF6, JAG1, KCTD1, KDF1, KDM6A, KMT2D,KREMEN1, LAMA3, LAMB3, LEF1, LRP4, LRP6, LTBP3, MEGF8, MKKS, MSX1, NECTIN4=PVRL4, NSD1, OFD1, P63, PAX3, PAX9, PHGDH, PITX2, PKP1, POC1A, POLR1D, POLR1C, POLR3A, POLR3B, POLR3GL, PORCN, PROK2, PROKR2, PVRL1, PVR4, RAB23, RECQL4, RNF216, RPS6KA3, RSK2, RUNX2, SATB2, SHH, SLC26A2, SLC29A3, SMOC2, SPECC1L, TBCE, TBX3, TBX22, TCOF1, TFAP2B, TP63, TSPEAR, UBR1, WDR19, WDR35, WNT10A, WNT10B.Depending on the gene involved, inheritance can follow different modes of inheritance. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.In some individuals, the disorder is due to a spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.
X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly 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. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working gene he will develop the disease.Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.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.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.
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Affects of Tooth Agenesis
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The prevalence of anodontia is unknown. This condition affects males and females in equal numbers. The prevalence of hypodontia is 2 to 8% of the general population (excluding third molar) and oligodontia is 0.09%. to 0.3%.
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Affects of Tooth Agenesis. The prevalence of anodontia is unknown. This condition affects males and females in equal numbers. The prevalence of hypodontia is 2 to 8% of the general population (excluding third molar) and oligodontia is 0.09%. to 0.3%.
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Related disorders of Tooth Agenesis
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The ectodermal dysplasias are a group of hereditary, non-progressive conditions affecting the development or function of the teeth, hair, nails and sweat glands, salivary glands, mammary glands, nasolacrimal ducts. (For more information, choose “Ectodermal Dysplasia” as your search term in the Rare Disease Database).Hypo/oligodontia might also be associated to cleft lip and palate in certain syndromes and associated with mutations is several different genes (MSX1, IRF6, LRP6…).A rare association was discovered linking tooth agenesis and susceptibility to colorectal cancer (AXIN2 gene mutations).
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Related disorders of Tooth Agenesis. The ectodermal dysplasias are a group of hereditary, non-progressive conditions affecting the development or function of the teeth, hair, nails and sweat glands, salivary glands, mammary glands, nasolacrimal ducts. (For more information, choose “Ectodermal Dysplasia” as your search term in the Rare Disease Database).Hypo/oligodontia might also be associated to cleft lip and palate in certain syndromes and associated with mutations is several different genes (MSX1, IRF6, LRP6…).A rare association was discovered linking tooth agenesis and susceptibility to colorectal cancer (AXIN2 gene mutations).
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Diagnosis of Tooth Agenesis
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The diagnosis of hypo/oligodontia or anodontia may be confirmed by dental X-rays. Other signs might be associated such as smaller teeth, peg shape lateral incisors, conical teeth, taurodontic molars, and spaced dentition.Genetic testing is available to identify mutations in 560 known and candidate genes involved in orodental diseases.
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Diagnosis of Tooth Agenesis. The diagnosis of hypo/oligodontia or anodontia may be confirmed by dental X-rays. Other signs might be associated such as smaller teeth, peg shape lateral incisors, conical teeth, taurodontic molars, and spaced dentition.Genetic testing is available to identify mutations in 560 known and candidate genes involved in orodental diseases.
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Therapies of Tooth Agenesis
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Treatment
Treatment of hypo/oligodontia or anodontia consists of artificial dentures. Artificial dentures are removable teeth that may aid in chewing and can improve the appearance of the mouth. In the case of oligodontia or according to the patient need, treatment might be started early. Removable prosthesis could be proposed for children who are 3-4 years old. These prostheses can be renewed as the child grows.If only front teeth are missing in hypodontia or oligodontia, a flexible system allowing slight movement of a bridge can be created by bonding an acrylic tooth to the supporting structure (abutments) by means of three orthodontic wires. Permanent options to replace missing teeth include dental implants.Therapeutic management of patients with hypo/oligodontia requires a multidisciplinary team including the pediatric dentist, orthodontist, a specialist in prosthodontics, and a maxillofacial surgeon.
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Therapies of Tooth Agenesis. Treatment
Treatment of hypo/oligodontia or anodontia consists of artificial dentures. Artificial dentures are removable teeth that may aid in chewing and can improve the appearance of the mouth. In the case of oligodontia or according to the patient need, treatment might be started early. Removable prosthesis could be proposed for children who are 3-4 years old. These prostheses can be renewed as the child grows.If only front teeth are missing in hypodontia or oligodontia, a flexible system allowing slight movement of a bridge can be created by bonding an acrylic tooth to the supporting structure (abutments) by means of three orthodontic wires. Permanent options to replace missing teeth include dental implants.Therapeutic management of patients with hypo/oligodontia requires a multidisciplinary team including the pediatric dentist, orthodontist, a specialist in prosthodontics, and a maxillofacial surgeon.
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Overview of Tooth and Nail Syndrome
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SummaryTooth and nail syndrome (TNS, also known as Witkop syndrome) is a rare genetic condition that belongs to a group of conditions called ectodermal dysplasias. This group has more than 100 separate syndromes and is defined by two or more symptoms in the nails, teeth, hair and/or skin. TNS is characterized by missing and/or incorrect formation of certain baby teeth (primary teeth) and permanent/adult teeth (secondary teeth) and incorrect formation of the nails. The lower lip of individuals with TNS may stick outwards, like a pout. TNS is usually diagnosed at 4-5 years of age when tooth and nail symptoms are found.Individuals who have TNS may have the following baby/adult teeth features: missing entirely, widely spaced, or shaped like cones (coniform). In addition, the nails in young children, especially the toenails, may be unusually small and underdeveloped (hypoplastic). They can have an obvious, unusual hollow shape, which appear to be spoon-shaped. They are slow-growing, thin and brittle. Nails are often more affected in childhood and can improve with age, so they may appear normal by adulthood. Individuals with TNS can have different numbers of teeth/nails affected, or various types of affected teeth. TNS is an autosomal dominant genetic condition.
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Overview of Tooth and Nail Syndrome. SummaryTooth and nail syndrome (TNS, also known as Witkop syndrome) is a rare genetic condition that belongs to a group of conditions called ectodermal dysplasias. This group has more than 100 separate syndromes and is defined by two or more symptoms in the nails, teeth, hair and/or skin. TNS is characterized by missing and/or incorrect formation of certain baby teeth (primary teeth) and permanent/adult teeth (secondary teeth) and incorrect formation of the nails. The lower lip of individuals with TNS may stick outwards, like a pout. TNS is usually diagnosed at 4-5 years of age when tooth and nail symptoms are found.Individuals who have TNS may have the following baby/adult teeth features: missing entirely, widely spaced, or shaped like cones (coniform). In addition, the nails in young children, especially the toenails, may be unusually small and underdeveloped (hypoplastic). They can have an obvious, unusual hollow shape, which appear to be spoon-shaped. They are slow-growing, thin and brittle. Nails are often more affected in childhood and can improve with age, so they may appear normal by adulthood. Individuals with TNS can have different numbers of teeth/nails affected, or various types of affected teeth. TNS is an autosomal dominant genetic condition.
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Symptoms of Tooth and Nail Syndrome
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TNS involves missing and/or the malformation of certain baby teeth (primary teeth) and permanent/adult teeth (secondary teeth). The number affected can range from 6 to 20 teeth. It also involves incorrect development of the nails. Rarely, affected individuals may also have changes affecting scalp hair, like thinning of the hair. Individuals with this condition usually have typical hair and sweat gland function. Symptoms are most obvious around school-age. TNS symptoms are less severe than other types of ectodermal dysplasia. Because of this, some people with TNS may be undiagnosed.In some infants with TNS, certain primary teeth may be missing or unusual in shape and look like cones (coniform) or are pointed. In most children with the condition, several secondary (adult) teeth are also absent and/or not properly formed. The most common adult teeth missing include the lower front teeth (mandibular incisors and the teeth next to the incisors). The upper portions (crowns) of certain permanent teeth may be cone-shaped and, and in some people the teeth may be widely spaced. Many infants and children with the disorder appear to have a “pouting” or outwardly turned lower lip (everted). This is due to the missing primary and/or secondary teeth. The jaw can also appear small due to incorrect tooth development. Tooth alignment is also affected, with some teeth growing in incorrectly. There is no standard pattern of missing teeth, and it varies with each individual.Individuals with TNS also have obvious differences in toenails and/or fingernails. The nails may be absent at birth and may grow very slowly. This typically occurs from infancy to around 2 to 3 years of age. In most individuals with TNS, the toenails are more affected than the fingernails. Sometimes the nails may appear normal in older children and adults, but toenails can continue to appear unusually small and/or spoon shaped. Nails can be rigid and break easily.Some individuals with TNS have scalp hair that is abnormally thin, fine and brittle. The hair is usually spaced around the head normally.
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Symptoms of Tooth and Nail Syndrome. TNS involves missing and/or the malformation of certain baby teeth (primary teeth) and permanent/adult teeth (secondary teeth). The number affected can range from 6 to 20 teeth. It also involves incorrect development of the nails. Rarely, affected individuals may also have changes affecting scalp hair, like thinning of the hair. Individuals with this condition usually have typical hair and sweat gland function. Symptoms are most obvious around school-age. TNS symptoms are less severe than other types of ectodermal dysplasia. Because of this, some people with TNS may be undiagnosed.In some infants with TNS, certain primary teeth may be missing or unusual in shape and look like cones (coniform) or are pointed. In most children with the condition, several secondary (adult) teeth are also absent and/or not properly formed. The most common adult teeth missing include the lower front teeth (mandibular incisors and the teeth next to the incisors). The upper portions (crowns) of certain permanent teeth may be cone-shaped and, and in some people the teeth may be widely spaced. Many infants and children with the disorder appear to have a “pouting” or outwardly turned lower lip (everted). This is due to the missing primary and/or secondary teeth. The jaw can also appear small due to incorrect tooth development. Tooth alignment is also affected, with some teeth growing in incorrectly. There is no standard pattern of missing teeth, and it varies with each individual.Individuals with TNS also have obvious differences in toenails and/or fingernails. The nails may be absent at birth and may grow very slowly. This typically occurs from infancy to around 2 to 3 years of age. In most individuals with TNS, the toenails are more affected than the fingernails. Sometimes the nails may appear normal in older children and adults, but toenails can continue to appear unusually small and/or spoon shaped. Nails can be rigid and break easily.Some individuals with TNS have scalp hair that is abnormally thin, fine and brittle. The hair is usually spaced around the head normally.
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Causes of Tooth and Nail Syndrome
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TNS is a genetic condition caused by a harmful change (mutation) in a gene. This leads to lack of a functional protein which ultimately causes the symptoms of TNS. The gene that causes TNS is called MSX1 and was discovered in 2001. This gene makes a protein that is important in tooth formation. Some mutations lead to a non-functioning protein resulting in TNS. Other rare MSX1 gene variants have been found to be associated with cleft lip and/or palate with or without missing teeth. Research has shown that harmful changes in the MSX1 gene affect the quality of a tooth layer called the mesenchyme. The MSX1 protein is involved in only certain stages of tooth development.TNS follows an autosomal dominant inheritance pattern. Dominant genetic conditions occur when only a single copy of a non-working gene is necessary to cause a particular condition. The non-working gene can be inherited from either parent or can be the result of a new (de novo) harmful change in the gene in the affected individual. The chance of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Causes of Tooth and Nail Syndrome. TNS is a genetic condition caused by a harmful change (mutation) in a gene. This leads to lack of a functional protein which ultimately causes the symptoms of TNS. The gene that causes TNS is called MSX1 and was discovered in 2001. This gene makes a protein that is important in tooth formation. Some mutations lead to a non-functioning protein resulting in TNS. Other rare MSX1 gene variants have been found to be associated with cleft lip and/or palate with or without missing teeth. Research has shown that harmful changes in the MSX1 gene affect the quality of a tooth layer called the mesenchyme. The MSX1 protein is involved in only certain stages of tooth development.TNS follows an autosomal dominant inheritance pattern. Dominant genetic conditions occur when only a single copy of a non-working gene is necessary to cause a particular condition. The non-working gene can be inherited from either parent or can be the result of a new (de novo) harmful change in the gene in the affected individual. The chance of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Affects of Tooth and Nail Syndrome
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TNS affects males and females in equal numbers. Since the condition was originally described in the medical literature in 1965 by C.J. Witkop, over 30 patients have been reported, with many in several families (kindreds). It has been estimated that 1-2 in every 10,000 individuals may be affected by TNS. The condition appears to be more common in Dutch Mennonites of Canada.
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Affects of Tooth and Nail Syndrome. TNS affects males and females in equal numbers. Since the condition was originally described in the medical literature in 1965 by C.J. Witkop, over 30 patients have been reported, with many in several families (kindreds). It has been estimated that 1-2 in every 10,000 individuals may be affected by TNS. The condition appears to be more common in Dutch Mennonites of Canada.
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Related disorders of Tooth and Nail Syndrome
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Symptoms of the following disorders may be similar to those of TNS. Comparisons may be useful in determining which diagnosis is correct.Fried syndrome, an extremely rare genetic condition, is also a form of ectodermal dysplasia. Fried syndrome and TNS have similar clinical features, but a different inheritance pattern. Fried syndrome is inherited as an autosomal recessive genetic condition.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The chance to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The chance is the same for males and females.In infants and children with the disorder, several primary (baby) teeth may be absent and/or unusually small, conical, and peg-shaped. It is unknown whether the secondary (permanent/adult) teeth are affected in the same way in all patients with Fried syndrome. Individuals with Fried syndrome have thin fingernails and unusually small, thin toenails that may be curved inward (concave). Affected individuals may also have slow growing, fine scalp hair and/or thin, small eyebrows. In TNS, the eyebrows are not affected. In addition, infants and children with Fried syndrome may appear to have an outwardly turned lower lip (everted). The symptoms of Fried syndrome are very similar to those occurring in TNS. However, in individuals with Fried syndrome, the nails are not as severely affected, and the hair is thin/fine.Hypohidrotic ectodermal dysplasia (also known as anhidrotic ectodermal dysplasia or Christ-Siemens-Touraine syndrome) is a rare genetic condition with features of missing and/or cone-shaped teeth. It also includes missing or underdevelopment of the sweat glands, fine, sparse, slow-growing hair and/or early-age baldness. People with this condition have differences of their face, such as a prominent forehead, sunken nasal bridge (“saddle” nose), and lips that are turned inside out (everted). Some individuals with this condition have short stature (height) and underdevelopment of the glands that release tears. Usually, this condition is inherited in an X-linked pattern so the full range of symptoms is seen only in males. However, females who carry a single copy of the disease gene may exhibit some mild symptoms. In other people, the condition may be inherited as an autosomal recessive condition and males and females are affected similarly. (For more information on this disorder, choose “hypohidrotic ectodermal dysplasia” as your search term in the Rare Disease Database.)Taurodontia, absent teeth, and sparse hair syndrome is a very rare genetic condition in which many teeth are missing. Symptoms also include incorrect formation of certain primary and/or secondary molars (taurodontia) and unusually sparse, slow-growing hair. In affected individuals, primary and/or secondary molars may be “prism” or “pyramid” shaped. Individuals with the condition may also have unusually thin, slow-growing, spoon-shaped fingernails and toenails. While it is unclear whether this disorder is completely separate from TNS, most consider it a separate diagnosis because misshapen molars are not usually associated with TNS. In addition, taurodontia, absent teeth and sparse hair syndrome is inherited as an autosomal recessive genetic condition.
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Related disorders of Tooth and Nail Syndrome. Symptoms of the following disorders may be similar to those of TNS. Comparisons may be useful in determining which diagnosis is correct.Fried syndrome, an extremely rare genetic condition, is also a form of ectodermal dysplasia. Fried syndrome and TNS have similar clinical features, but a different inheritance pattern. Fried syndrome is inherited as an autosomal recessive genetic condition.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The chance to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The chance is the same for males and females.In infants and children with the disorder, several primary (baby) teeth may be absent and/or unusually small, conical, and peg-shaped. It is unknown whether the secondary (permanent/adult) teeth are affected in the same way in all patients with Fried syndrome. Individuals with Fried syndrome have thin fingernails and unusually small, thin toenails that may be curved inward (concave). Affected individuals may also have slow growing, fine scalp hair and/or thin, small eyebrows. In TNS, the eyebrows are not affected. In addition, infants and children with Fried syndrome may appear to have an outwardly turned lower lip (everted). The symptoms of Fried syndrome are very similar to those occurring in TNS. However, in individuals with Fried syndrome, the nails are not as severely affected, and the hair is thin/fine.Hypohidrotic ectodermal dysplasia (also known as anhidrotic ectodermal dysplasia or Christ-Siemens-Touraine syndrome) is a rare genetic condition with features of missing and/or cone-shaped teeth. It also includes missing or underdevelopment of the sweat glands, fine, sparse, slow-growing hair and/or early-age baldness. People with this condition have differences of their face, such as a prominent forehead, sunken nasal bridge (“saddle” nose), and lips that are turned inside out (everted). Some individuals with this condition have short stature (height) and underdevelopment of the glands that release tears. Usually, this condition is inherited in an X-linked pattern so the full range of symptoms is seen only in males. However, females who carry a single copy of the disease gene may exhibit some mild symptoms. In other people, the condition may be inherited as an autosomal recessive condition and males and females are affected similarly. (For more information on this disorder, choose “hypohidrotic ectodermal dysplasia” as your search term in the Rare Disease Database.)Taurodontia, absent teeth, and sparse hair syndrome is a very rare genetic condition in which many teeth are missing. Symptoms also include incorrect formation of certain primary and/or secondary molars (taurodontia) and unusually sparse, slow-growing hair. In affected individuals, primary and/or secondary molars may be “prism” or “pyramid” shaped. Individuals with the condition may also have unusually thin, slow-growing, spoon-shaped fingernails and toenails. While it is unclear whether this disorder is completely separate from TNS, most consider it a separate diagnosis because misshapen molars are not usually associated with TNS. In addition, taurodontia, absent teeth and sparse hair syndrome is inherited as an autosomal recessive genetic condition.
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Diagnosis of Tooth and Nail Syndrome
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TNS may be suspected at birth if one or more toenails and/or fingernails are absent. More commonly, the condition is diagnosed at around four or five years of age, when certain primary (baby) teeth are missing and underdevelopment of nails may be noted. In some people, a diagnosis of TNS may not be confirmed until seven to fifteen years of age. This can be when the missing and/or unusual shape of several permanent, adult teeth and nail dysplasia has been confirmed. A diagnosis of TNS is confirmed based upon a thorough clinical exam noting the typical physical findings. Molecular genetic testing can also confirm a diagnosis. However, the percentage of patients with a clinical diagnosis of TNS and an identifiable mutation in the MSX1 gene is currently unknown.
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Diagnosis of Tooth and Nail Syndrome. TNS may be suspected at birth if one or more toenails and/or fingernails are absent. More commonly, the condition is diagnosed at around four or five years of age, when certain primary (baby) teeth are missing and underdevelopment of nails may be noted. In some people, a diagnosis of TNS may not be confirmed until seven to fifteen years of age. This can be when the missing and/or unusual shape of several permanent, adult teeth and nail dysplasia has been confirmed. A diagnosis of TNS is confirmed based upon a thorough clinical exam noting the typical physical findings. Molecular genetic testing can also confirm a diagnosis. However, the percentage of patients with a clinical diagnosis of TNS and an identifiable mutation in the MSX1 gene is currently unknown.
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Therapies of Tooth and Nail Syndrome
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TreatmentThe treatment of TNS is directed toward the specific symptoms and findings that are present. The severity may vary from person to person, but the condition of the hair and nails usually gets better when patients get older. Pediatricians, dental surgeons, dental specialists who diagnose and/orcorrect wrongly aligned teeth (orthodontists) are involved in the care of people with TNS. Other health care professionals may also be involved to ensure a complete approach to treatment.Treatment mainly consists of restoring teeth. Artificial teeth and/or other devices (prosthetics) may be used to replace missing teeth. Devices can help with spacing of teeth as well. In addition, braces, dental surgery and/or other corrective procedures may be used to help with these dental differences. Bonding of conical shaped teeth in young individuals improves the look and chewing ability of teeth. It is best to have dental work done at an earlier age, with the first visit during the first year, and visits every 6-12 months. Dental work may be needed every 2-3 years.Dietary counseling may be helpful for patients who have trouble chewing and swallowing.Patients may feel self-conscious due to their appearance, so psychological support may be helpful.Genetic counseling may be recommended for patients and their families.
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Therapies of Tooth and Nail Syndrome. TreatmentThe treatment of TNS is directed toward the specific symptoms and findings that are present. The severity may vary from person to person, but the condition of the hair and nails usually gets better when patients get older. Pediatricians, dental surgeons, dental specialists who diagnose and/orcorrect wrongly aligned teeth (orthodontists) are involved in the care of people with TNS. Other health care professionals may also be involved to ensure a complete approach to treatment.Treatment mainly consists of restoring teeth. Artificial teeth and/or other devices (prosthetics) may be used to replace missing teeth. Devices can help with spacing of teeth as well. In addition, braces, dental surgery and/or other corrective procedures may be used to help with these dental differences. Bonding of conical shaped teeth in young individuals improves the look and chewing ability of teeth. It is best to have dental work done at an earlier age, with the first visit during the first year, and visits every 6-12 months. Dental work may be needed every 2-3 years.Dietary counseling may be helpful for patients who have trouble chewing and swallowing.Patients may feel self-conscious due to their appearance, so psychological support may be helpful.Genetic counseling may be recommended for patients and their families.
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Overview of TORCH Syndrome
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TORCH Syndrome refers to infection of a developing fetus or newborn by any of a group of infectious agents. “TORCH” is an acronym meaning (T)oxoplasmosis, (O)ther Agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes Simplex. Infection with any of these agents (i.e., Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex viruses) may cause a constellation of similar symptoms in affected newborns. These may include fever; difficulties feeding; small areas of bleeding under the skin, causing the appearance of small reddish or purplish spots; enlargement of the liver and spleen (hepatosplenomegaly); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); hearing impairment; abnormalities of the eyes; and/or other symptoms and findings. Each infectious agent may also result in additional abnormalities that may be variable, depending upon a number of factors (e.g., stage of fetal development).
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Overview of TORCH Syndrome. TORCH Syndrome refers to infection of a developing fetus or newborn by any of a group of infectious agents. “TORCH” is an acronym meaning (T)oxoplasmosis, (O)ther Agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes Simplex. Infection with any of these agents (i.e., Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex viruses) may cause a constellation of similar symptoms in affected newborns. These may include fever; difficulties feeding; small areas of bleeding under the skin, causing the appearance of small reddish or purplish spots; enlargement of the liver and spleen (hepatosplenomegaly); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); hearing impairment; abnormalities of the eyes; and/or other symptoms and findings. Each infectious agent may also result in additional abnormalities that may be variable, depending upon a number of factors (e.g., stage of fetal development).
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Symptoms of TORCH Syndrome
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TORCH Syndrome refers to any of a group of infections in newborns due to one of the TORCH infectious agents having crossed the placenta during pregnancy. The acronym TORCH refers to (T)oxoplasmosis, (O)ther Agents, (R)ubella (or German Measles), (C)ytomegalovirus, and (H)erpes Simplex. If a developing fetus is infected by a TORCH agent, the outcome of the pregnancy may be miscarriage, stillbirth, delayed fetal growth and maturation (intrauterine growth retardation), or early delivery. In addition, newborns infected by any one of the TORCH agents may develop a spectrum of similar symptoms and findings. These may include listlessness (lethargy), fever, difficulties feeding, enlargement of the liver and spleen (hepatomegaly), and decreased levels of the oxygen-carrying pigment (hemoglobin) in the blood (anemia). In addition, affected infants may develop areas of bleeding, resulting in reddish or purplish spots or areas of discoloration visible through the skin (petechia or purpura); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); inflammation of the middle and innermost layers of the eyes (chorioretinitis); and/or other symptoms and findings. Each infectious agent may also cause additional abnormalities that may vary in degree and severity, depending upon the stage of fetal development at time of infection and/or other factors. Following is a more specific description of the TORCH agents.Toxoplasmosis is an infectious disease caused by the microscopic parasitic organism called Toxoplasma gondii. This parasitic infection, found worldwide, may be acquired or transmitted to the developing fetus from an infected mother during pregnancy. In some severely affected newborns, Toxoplasmosis may be associated with abnormal smallness of the head (microcephaly), inflammation of the middle and innermost layers of the eyes (chorioretinitis), calcium deposits in the brain (intracranial calcifications), and/or other abnormalities. (For more information on this disorder, choose “Toxoplasmosis” as your search term in the Rare Disease Database.)Rubella is a viral infection characterized by fever, upper respiratory infection, swelling of the lymph nodes, skin rash, and joint pain. Severely affected newborns and infants may have visual and/or hearing impairment, heart defects, calcium deposits in the brain, and/or other abnormalities. (For more information on this disorder, choose “Rubella” as your search term in the Rare Disease Database.)Cytomegalovirus (CMV) Infection is a viral infection that may occur during pregnancy, after birth, or at any age. In severely affected newborns, associated symptoms and findings may include growth retardation, an abnormally small head (microcephaly), enlargement of the liver and spleen (hepatosplenomegaly), inflammation of the liver (hepatitis), low levels of the oxygen-carrying pigment in the blood due to premature destruction of red blood cells (hemolytic anemia), calcium deposits in the brain, and/or other abnormalities. (For more information on this disorder, choose “Cytomegalovirus” as your search term in the Rare Disease Database.)Neonatal Herpes is a rare disorder affecting newborns infected with the Herpes simplex virus (HSV). This disorder may vary from mild to severe. In most cases, the disorder is transmitted to an infant from an infected mother with active genital lesions at the time of delivery. In the event that a mother has a severe primary genital outbreak, it is possible that a mother may transmit the infection to the fetus. After delivery, direct contact with either genital or oral herpes sores may result in neonatal herpes. Severely affected newborns may develop fluid-filled blisters on the skin (cutaneous vesicles), lesions in the mouth area, inflammation of the mucous membrane lining the eyelids and whites of the eyes (conjunctivitis), abnormally diminished muscle tone, inflammation of the liver (hepatitis), difficulties breathing, and/or other symptoms and findings. (For more information on this disorder, choose “Neonatal Herpes” as your search term in the Rare Disease Database.)
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Symptoms of TORCH Syndrome. TORCH Syndrome refers to any of a group of infections in newborns due to one of the TORCH infectious agents having crossed the placenta during pregnancy. The acronym TORCH refers to (T)oxoplasmosis, (O)ther Agents, (R)ubella (or German Measles), (C)ytomegalovirus, and (H)erpes Simplex. If a developing fetus is infected by a TORCH agent, the outcome of the pregnancy may be miscarriage, stillbirth, delayed fetal growth and maturation (intrauterine growth retardation), or early delivery. In addition, newborns infected by any one of the TORCH agents may develop a spectrum of similar symptoms and findings. These may include listlessness (lethargy), fever, difficulties feeding, enlargement of the liver and spleen (hepatomegaly), and decreased levels of the oxygen-carrying pigment (hemoglobin) in the blood (anemia). In addition, affected infants may develop areas of bleeding, resulting in reddish or purplish spots or areas of discoloration visible through the skin (petechia or purpura); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); inflammation of the middle and innermost layers of the eyes (chorioretinitis); and/or other symptoms and findings. Each infectious agent may also cause additional abnormalities that may vary in degree and severity, depending upon the stage of fetal development at time of infection and/or other factors. Following is a more specific description of the TORCH agents.Toxoplasmosis is an infectious disease caused by the microscopic parasitic organism called Toxoplasma gondii. This parasitic infection, found worldwide, may be acquired or transmitted to the developing fetus from an infected mother during pregnancy. In some severely affected newborns, Toxoplasmosis may be associated with abnormal smallness of the head (microcephaly), inflammation of the middle and innermost layers of the eyes (chorioretinitis), calcium deposits in the brain (intracranial calcifications), and/or other abnormalities. (For more information on this disorder, choose “Toxoplasmosis” as your search term in the Rare Disease Database.)Rubella is a viral infection characterized by fever, upper respiratory infection, swelling of the lymph nodes, skin rash, and joint pain. Severely affected newborns and infants may have visual and/or hearing impairment, heart defects, calcium deposits in the brain, and/or other abnormalities. (For more information on this disorder, choose “Rubella” as your search term in the Rare Disease Database.)Cytomegalovirus (CMV) Infection is a viral infection that may occur during pregnancy, after birth, or at any age. In severely affected newborns, associated symptoms and findings may include growth retardation, an abnormally small head (microcephaly), enlargement of the liver and spleen (hepatosplenomegaly), inflammation of the liver (hepatitis), low levels of the oxygen-carrying pigment in the blood due to premature destruction of red blood cells (hemolytic anemia), calcium deposits in the brain, and/or other abnormalities. (For more information on this disorder, choose “Cytomegalovirus” as your search term in the Rare Disease Database.)Neonatal Herpes is a rare disorder affecting newborns infected with the Herpes simplex virus (HSV). This disorder may vary from mild to severe. In most cases, the disorder is transmitted to an infant from an infected mother with active genital lesions at the time of delivery. In the event that a mother has a severe primary genital outbreak, it is possible that a mother may transmit the infection to the fetus. After delivery, direct contact with either genital or oral herpes sores may result in neonatal herpes. Severely affected newborns may develop fluid-filled blisters on the skin (cutaneous vesicles), lesions in the mouth area, inflammation of the mucous membrane lining the eyelids and whites of the eyes (conjunctivitis), abnormally diminished muscle tone, inflammation of the liver (hepatitis), difficulties breathing, and/or other symptoms and findings. (For more information on this disorder, choose “Neonatal Herpes” as your search term in the Rare Disease Database.)
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Causes of TORCH Syndrome
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TORCH Syndrome results from one of the TORCH agents having crossed the placenta during pregnancy. These infectious agents include Toxoplasma gondii, the single-celled microorganism (protozoa) responsible for Toxoplasmosis; rubella virus; cytomegalovirus; and herpes simplex viruses. (Note: According to some reports, the acronym “TORCH” is sometimes modified to the term “STORCH” to include syphilis, a disease that may result in symptoms similar to those associated with the other TORCH agents. Syphilis is caused by infection with the bacterium Treponema pallidum. In addition, TORCH may encompass other disease-causing agents, such as varicella-zoster virus, which is the virus responsible for chickenpox, and parvovirus.)
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Causes of TORCH Syndrome. TORCH Syndrome results from one of the TORCH agents having crossed the placenta during pregnancy. These infectious agents include Toxoplasma gondii, the single-celled microorganism (protozoa) responsible for Toxoplasmosis; rubella virus; cytomegalovirus; and herpes simplex viruses. (Note: According to some reports, the acronym “TORCH” is sometimes modified to the term “STORCH” to include syphilis, a disease that may result in symptoms similar to those associated with the other TORCH agents. Syphilis is caused by infection with the bacterium Treponema pallidum. In addition, TORCH may encompass other disease-causing agents, such as varicella-zoster virus, which is the virus responsible for chickenpox, and parvovirus.)
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Affects of TORCH Syndrome
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TORCH syndrome may affect a developing fetus or newborn, potentially resulting in miscarriage, delayed fetal growth and maturation (intrauterine growth retardation), or early delivery.
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Affects of TORCH Syndrome. TORCH syndrome may affect a developing fetus or newborn, potentially resulting in miscarriage, delayed fetal growth and maturation (intrauterine growth retardation), or early delivery.
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Related disorders of TORCH Syndrome
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Related disorders of TORCH Syndrome.
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Diagnosis of TORCH Syndrome
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Diagnosis of TORCH Syndrome.
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Therapies of TORCH Syndrome
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Treatment of newborns and infants with TORCH Syndrome is based upon the specific causative agent, the stage of fetal development when infection initially occurred, the severity of the infection and associated symptoms and findings, and/or other factors. For infants with toxoplasmosis, treatment may include administration of the medication pyrimethamine with sulfadiazine. Herpes simplex may be treated with the antiviral agent acyclovir. The treatment of newborns and infants with rubella or cytomegalovirus primarily includes symptomatic and supportive measures.
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Therapies of TORCH Syndrome. Treatment of newborns and infants with TORCH Syndrome is based upon the specific causative agent, the stage of fetal development when infection initially occurred, the severity of the infection and associated symptoms and findings, and/or other factors. For infants with toxoplasmosis, treatment may include administration of the medication pyrimethamine with sulfadiazine. Herpes simplex may be treated with the antiviral agent acyclovir. The treatment of newborns and infants with rubella or cytomegalovirus primarily includes symptomatic and supportive measures.
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Overview of Townes-Brocks Syndrome
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SummaryTownes-Brocks syndrome (TBS) is a genetic condition caused by a harmful change (mutation) in a gene called SALL1. Features include no anal opening (imperforate anus) and differently shaped ears and thumbs. There can also be problems with the feet, heart and kidneys.
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Overview of Townes-Brocks Syndrome. SummaryTownes-Brocks syndrome (TBS) is a genetic condition caused by a harmful change (mutation) in a gene called SALL1. Features include no anal opening (imperforate anus) and differently shaped ears and thumbs. There can also be problems with the feet, heart and kidneys.
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Symptoms of Townes-Brocks Syndrome
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There are three major symptoms of TBS: A closed anal opening (imperforate anus), small ears that usually have a folded rim of skin and cartilage around the outer ear, and differences in the structures of the thumbs. The thumbs have three bones (triphalangeal) instead of two. People with this syndrome may also have an extra thumb (preaxial polydactyly). Another symptom may be hearing loss present at birth (congenital). The hearing loss can be sensorineural and/or conductive, range from mild to severe and may be progressive. Differences in the feet occur less frequently and include a short third toe, overlapping toes and flat feet. Typical kidney (renal) differences include displaced or rotated kidneys, horseshoe kidney, polycystic kidneys and underdeveloped kidneys. There can also be heart and genital problems present at birth. Intellectual disability occurs in about 10% of affected individuals.
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Symptoms of Townes-Brocks Syndrome. There are three major symptoms of TBS: A closed anal opening (imperforate anus), small ears that usually have a folded rim of skin and cartilage around the outer ear, and differences in the structures of the thumbs. The thumbs have three bones (triphalangeal) instead of two. People with this syndrome may also have an extra thumb (preaxial polydactyly). Another symptom may be hearing loss present at birth (congenital). The hearing loss can be sensorineural and/or conductive, range from mild to severe and may be progressive. Differences in the feet occur less frequently and include a short third toe, overlapping toes and flat feet. Typical kidney (renal) differences include displaced or rotated kidneys, horseshoe kidney, polycystic kidneys and underdeveloped kidneys. There can also be heart and genital problems present at birth. Intellectual disability occurs in about 10% of affected individuals.
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Causes of Townes-Brocks Syndrome
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TBS is caused by a harmful genetic change (mutation) in a gene called SALL1. The SALL1 gene has instructions for the body to form certain tissues and organs such as the hands (particularly the thumbs), ears, anus and kidneys. Humans should have two working copies of the SALL1 gene, but people with TBS have one copy of the gene that does not work properly.There is also evidence that this condition could be caused by a mutation in the DACT1 gene, but a mutation in the SALL1 gene is the more common cause.TBS is inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Causes of Townes-Brocks Syndrome. TBS is caused by a harmful genetic change (mutation) in a gene called SALL1. The SALL1 gene has instructions for the body to form certain tissues and organs such as the hands (particularly the thumbs), ears, anus and kidneys. Humans should have two working copies of the SALL1 gene, but people with TBS have one copy of the gene that does not work properly.There is also evidence that this condition could be caused by a mutation in the DACT1 gene, but a mutation in the SALL1 gene is the more common cause.TBS is inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Affects of Townes-Brocks Syndrome
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It has been estimated that TBS occurs in at least 1 in 250,000 births.
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Affects of Townes-Brocks Syndrome. It has been estimated that TBS occurs in at least 1 in 250,000 births.
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Related disorders of Townes-Brocks Syndrome
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The physical features of TBS are similar to oculo-auriculo-vertebral spectrum disorder, Okihiro syndrome, branchiootorenal syndrome, VACTERL association and STAR syndrome.People with oculo-auriculo-vertebral spectrum disorder can have a wide range of problems affecting the eyes, ears and spine. In some forms, one side of the face may be underdeveloped (hemifacial microstomia). Patients with TBS can also have hemifacial microstomia. (For more information about this disorder, choose “oculo-auriculo-vertebral spectrum” as your search term in the Rare Disease Database.)Okihiro syndrome (Duane-radial ray syndrome) affects the eyes and causes differences of bones in the arms and hands. Bone changes in the hands include structurally different or absent thumbs, an extra thumb or a thumb that looks like a finger. There is limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction) or in both directions.Branchiootorenal spectrum disorders are associated with pits or ear tags in front of the outer ear, and kidney defects or impaired renal function. There are no other TBS associated symptoms. It is also associated with abnormal passages from the throat to the outside surface of the neck (branchial fistulas), branchial cysts and hearing loss. (For more information about this disorder, choose “branchiootorenal spectrum” as your search term in the Rare Disease Database.)VACTERL association is a nonrandom association of birth defects that affects multiple anatomical structures. The term VACTERL is an acronym with each letter representing the first letter of one of the more common findings seen in affected children: (V) = vertebral (spinal) abnormalities, (A) = anal atresia, (C) = cardiac (heart) defects, (T) = tracheoesophageal fistula, (E) =esophageal atresia, (R) = renal (kidney) abnormalities and (L) = limb abnormalities. TBS does not have the vertebral defects. (For more information about this disorder, choose “VACTERL” as your search term in the Rare Disease Database.)STAR syndrome is associated with fusion of the toes (syndactyly), wide-spaced eyes (telecanthus), and anal, genital and kidney defects similar to TBS. The facial features and toe fusion are the differences between STAR syndrome and TBS. This syndrome also more commonly affects males due to the X-linked inheritance pattern.
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Related disorders of Townes-Brocks Syndrome. The physical features of TBS are similar to oculo-auriculo-vertebral spectrum disorder, Okihiro syndrome, branchiootorenal syndrome, VACTERL association and STAR syndrome.People with oculo-auriculo-vertebral spectrum disorder can have a wide range of problems affecting the eyes, ears and spine. In some forms, one side of the face may be underdeveloped (hemifacial microstomia). Patients with TBS can also have hemifacial microstomia. (For more information about this disorder, choose “oculo-auriculo-vertebral spectrum” as your search term in the Rare Disease Database.)Okihiro syndrome (Duane-radial ray syndrome) affects the eyes and causes differences of bones in the arms and hands. Bone changes in the hands include structurally different or absent thumbs, an extra thumb or a thumb that looks like a finger. There is limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction) or in both directions.Branchiootorenal spectrum disorders are associated with pits or ear tags in front of the outer ear, and kidney defects or impaired renal function. There are no other TBS associated symptoms. It is also associated with abnormal passages from the throat to the outside surface of the neck (branchial fistulas), branchial cysts and hearing loss. (For more information about this disorder, choose “branchiootorenal spectrum” as your search term in the Rare Disease Database.)VACTERL association is a nonrandom association of birth defects that affects multiple anatomical structures. The term VACTERL is an acronym with each letter representing the first letter of one of the more common findings seen in affected children: (V) = vertebral (spinal) abnormalities, (A) = anal atresia, (C) = cardiac (heart) defects, (T) = tracheoesophageal fistula, (E) =esophageal atresia, (R) = renal (kidney) abnormalities and (L) = limb abnormalities. TBS does not have the vertebral defects. (For more information about this disorder, choose “VACTERL” as your search term in the Rare Disease Database.)STAR syndrome is associated with fusion of the toes (syndactyly), wide-spaced eyes (telecanthus), and anal, genital and kidney defects similar to TBS. The facial features and toe fusion are the differences between STAR syndrome and TBS. This syndrome also more commonly affects males due to the X-linked inheritance pattern.
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Diagnosis of Townes-Brocks Syndrome
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The clinical diagnosis of TBS is based on the presence of the three common symptoms (differences of the anus, ear and thumb) and sometimes the minor features. Genetic testing that reveals a harmful variant in the SALL1 gene can confirm the diagnosis.
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Diagnosis of Townes-Brocks Syndrome. The clinical diagnosis of TBS is based on the presence of the three common symptoms (differences of the anus, ear and thumb) and sometimes the minor features. Genetic testing that reveals a harmful variant in the SALL1 gene can confirm the diagnosis.
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Therapies of Townes-Brocks Syndrome
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Treatment includes surgery to correct the differences of the anus and thumbs. Hearing evaluation should be conducted if TBS is suspected. Ultrasound and laboratory tests should be performed to monitor kidney function. A baseline echocardiogram should be performed by a cardiologist.Genetic counseling is recommended for affected individuals and their families.
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Therapies of Townes-Brocks Syndrome. Treatment includes surgery to correct the differences of the anus and thumbs. Hearing evaluation should be conducted if TBS is suspected. Ultrasound and laboratory tests should be performed to monitor kidney function. A baseline echocardiogram should be performed by a cardiologist.Genetic counseling is recommended for affected individuals and their families.
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Overview of Toxic Shock Syndrome
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Toxic Shock Syndrome is a rare multisystem disease with many widespread symptoms. It is caused by a toxin that is produced and secreted by the bacterium Staphylococcus aureus. The symptoms of Toxic Shock Syndrome may include a sudden high fever, nausea, vomiting, diarrhea, abnormally low blood pressure (hypotension), and a characteristic skin rash that resemble a bad sunburn. Most cases of Toxic Shock Syndrome occur in menstruating females in association with the use of tampons. Other cases may occur in association with postoperative wound infections, nasal packing, or other factors.
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Overview of Toxic Shock Syndrome. Toxic Shock Syndrome is a rare multisystem disease with many widespread symptoms. It is caused by a toxin that is produced and secreted by the bacterium Staphylococcus aureus. The symptoms of Toxic Shock Syndrome may include a sudden high fever, nausea, vomiting, diarrhea, abnormally low blood pressure (hypotension), and a characteristic skin rash that resemble a bad sunburn. Most cases of Toxic Shock Syndrome occur in menstruating females in association with the use of tampons. Other cases may occur in association with postoperative wound infections, nasal packing, or other factors.
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Symptoms of Toxic Shock Syndrome
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The symptoms of Toxic Shock Syndrome begin suddenly and usually include high fever, headache, sore throat (pharyngitis), inflammation of the whites of the eyes (conjunctivitis), muscle aches and pain (myalgia), and/or certain digestive symptoms, such as nausea, vomiting, and profuse watery diarrhea. Involvement of the central nervous system is also common and may be characterized by listlessness, dizziness, confusion, and/or disorientation. A characteristic “sunburn-like” skin rash typically develops within a few hours of onset, with later scaling and peeling (desquamation) of skin, particularly of the palms and soles.In severe cases, blood pressure may fall dangerously low (hypotension), with an inadequate blood supply to body tissues (shock). Additional complications may include kidney and/or liver failure, heart dysfunction, adult respiratory distress syndrome, and/or other abnormalities. Adult respiratory distress syndrome is characterized by shortness of breath (dyspnea), abnormally rapid breathing, and insufficient levels of oxygen in the circulating blood. Without early diagnosis and appropriate treatment of Toxic Shock Syndrome, potentially life-threatening complications may result.
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Symptoms of Toxic Shock Syndrome. The symptoms of Toxic Shock Syndrome begin suddenly and usually include high fever, headache, sore throat (pharyngitis), inflammation of the whites of the eyes (conjunctivitis), muscle aches and pain (myalgia), and/or certain digestive symptoms, such as nausea, vomiting, and profuse watery diarrhea. Involvement of the central nervous system is also common and may be characterized by listlessness, dizziness, confusion, and/or disorientation. A characteristic “sunburn-like” skin rash typically develops within a few hours of onset, with later scaling and peeling (desquamation) of skin, particularly of the palms and soles.In severe cases, blood pressure may fall dangerously low (hypotension), with an inadequate blood supply to body tissues (shock). Additional complications may include kidney and/or liver failure, heart dysfunction, adult respiratory distress syndrome, and/or other abnormalities. Adult respiratory distress syndrome is characterized by shortness of breath (dyspnea), abnormally rapid breathing, and insufficient levels of oxygen in the circulating blood. Without early diagnosis and appropriate treatment of Toxic Shock Syndrome, potentially life-threatening complications may result.
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Causes of Toxic Shock Syndrome
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Toxic Shock Syndrome (TSS) is a rare acute multisystemic disease caused by toxins (such as “toxic shock syndrome toxin-1” [TSST-1], enterotoxin B, enterotoxin C) produced by certain strains (particularly phage group I) of the bacterium Staphylococcus aureus (S. aureus). TSS is most common in menstruating women who use highly absorbent tampons. Evidence suggests that the prolonged use of tampons in the presence (i.e., colonization) of toxin-secreting S. aureus strains may promote increased production of the toxin, which may enter the bloodstream through the uterus or tiny cuts within the vaginal lining.In addition, TSS may also occur in nonmenstruating women or those who do not use tampons. Such “nonmenstrual TSS” may occur due to vaginal colonization of toxin-secreting S. aureus strains and certain associated factors, such as the use of vaginal contraceptive devices (e.g., diaphragms, contraceptive sponges); vaginal infection; childbirth or the period (e.g., hours to several weeks) following delivery (postpartum state); or other factors. Nonmenstrual TSS may also occur in women, men, or children in association with post-surgical wounds; nasal packing; burns; certain skin infections; other inflammatory conditions, such as of the windpipe (tracheitis), the sinuses (sinusitis), the lungs (pneumonia), or the bone or bone marrow (osteomyelitis); the “flu” (influenza); or other factors.
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Causes of Toxic Shock Syndrome. Toxic Shock Syndrome (TSS) is a rare acute multisystemic disease caused by toxins (such as “toxic shock syndrome toxin-1” [TSST-1], enterotoxin B, enterotoxin C) produced by certain strains (particularly phage group I) of the bacterium Staphylococcus aureus (S. aureus). TSS is most common in menstruating women who use highly absorbent tampons. Evidence suggests that the prolonged use of tampons in the presence (i.e., colonization) of toxin-secreting S. aureus strains may promote increased production of the toxin, which may enter the bloodstream through the uterus or tiny cuts within the vaginal lining.In addition, TSS may also occur in nonmenstruating women or those who do not use tampons. Such “nonmenstrual TSS” may occur due to vaginal colonization of toxin-secreting S. aureus strains and certain associated factors, such as the use of vaginal contraceptive devices (e.g., diaphragms, contraceptive sponges); vaginal infection; childbirth or the period (e.g., hours to several weeks) following delivery (postpartum state); or other factors. Nonmenstrual TSS may also occur in women, men, or children in association with post-surgical wounds; nasal packing; burns; certain skin infections; other inflammatory conditions, such as of the windpipe (tracheitis), the sinuses (sinusitis), the lungs (pneumonia), or the bone or bone marrow (osteomyelitis); the “flu” (influenza); or other factors.
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Affects of Toxic Shock Syndrome
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Toxic Shock Syndrome (TSS) was originally described as a disease entity in 1978, when the condition was reported in seven children from age eight to 17 years. In 1980 and 1981, a large number of TSS cases were recognized, primarily in young menstruating women who used tampons. This sudden increase was thought to be due to the introduction and availability of new, highly absorbent tampons.Since the removal of super absorbent tampon varieties from the market and the introduction of federal regulations, the incidence of TSS has declined in women in the United States. (Incidence refers to the number of new cases of a particular disorder or condition during a specific period.) For example, in 1980 in the U.S., the incidence of TSS was approximately six per 100,000 women aged 19 to 44 years. In 1986 and later, the incidence decreased among this age group to one per 100,000. Other estimates suggest that TSS may currently occur in up to three per 100,000 menstruating women. Investigators indicate that menstruation-associated TSS most commonly occurs in young women aged 15 to 25 years who are using tampons.As noted above, TSS may also occur in nonmenstruating women and in women who do not use tampons as well as in men and children. Nonmenstrual TSS more commonly affects females than males by a ratio of about three to one. (For further information, please see the “Causes” section above.)
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Affects of Toxic Shock Syndrome. Toxic Shock Syndrome (TSS) was originally described as a disease entity in 1978, when the condition was reported in seven children from age eight to 17 years. In 1980 and 1981, a large number of TSS cases were recognized, primarily in young menstruating women who used tampons. This sudden increase was thought to be due to the introduction and availability of new, highly absorbent tampons.Since the removal of super absorbent tampon varieties from the market and the introduction of federal regulations, the incidence of TSS has declined in women in the United States. (Incidence refers to the number of new cases of a particular disorder or condition during a specific period.) For example, in 1980 in the U.S., the incidence of TSS was approximately six per 100,000 women aged 19 to 44 years. In 1986 and later, the incidence decreased among this age group to one per 100,000. Other estimates suggest that TSS may currently occur in up to three per 100,000 menstruating women. Investigators indicate that menstruation-associated TSS most commonly occurs in young women aged 15 to 25 years who are using tampons.As noted above, TSS may also occur in nonmenstruating women and in women who do not use tampons as well as in men and children. Nonmenstrual TSS more commonly affects females than males by a ratio of about three to one. (For further information, please see the “Causes” section above.)
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Related disorders of Toxic Shock Syndrome
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Symptoms of the following disorders may be similar to those of Toxic Shock Syndrome (TSS). Comparisons may be useful for a differential diagnosis:Streptococcal Toxic Shock Syndrome may be characterized by TSS-like symptoms and findings, the sudden onset of shock, and impairment of various organ systems due to infection with certain toxin-secreting strains of streptococcus bacteria (group A beta-hemolytic streptococci). The syndrome, which was initially reported in the mid to late 1980s, may occur in adults or children. The skin and soft tissues are usually the primary sites of infection. Factors that appear to increase the risk of infection may include certain surgical procedures, particular viral infections (e.g., varicella, influenza), and exposure to affected individuals in close environments such as hospitals or nursing homes. Associated symptoms and findings may vary from case to case, depending upon the causative bacterial strain and other factors. Reported features have included initial flu-like symptoms, including fever, chills, muscle aches, and vomiting; low blood pressure (hypotension); confusion; an accelerated heart rate (tachycardia), unusually rapid breathing (tachypnea), and other findings; and sudden onset of shock and multiple organ failure, leading to potentially life-threatening complications.Scarlet Fever is an infectious disease of childhood usually caused by certain toxin-secreting strains of streptococci bacteria (group A beta-hemolytic streptococci). Symptoms may include sore throat, fever, chills, swollen lymph nodes in the neck, a strawberry color to the tongue, and the development of a pinkish-red rash that may be most apparent on the sides of the chest, on the abdomen, and within skin folds. Following resolution of fever, the outer region of previously reddened skin may peel. Other symptoms and findings may also be present.Kawasaki Disease is a rare inflammatory disease of unknown cause that most commonly affects infants and young children. It may be characterized by a sudden fever that lasts for approximately one week or longer; dryness and cracking of the lips; a strawberry-red tongue; swelling of one or more lymph nodes (lymphadenopathy); and/or a reddish skin rash affecting the hands and feet, trunk, and other regions. By about two to three weeks following symptom onset, affected skin tissue may peel (desquamate) from the tips of the fingers and toes, palms of the hands, soles of the feet, and/or other affected areas. Other symptoms and findings may include inflammation and redness of the “whites” of the eyes (bilateral conjunctivitis); irritability; fatigue; inflammation, pain, and swelling of many joints (polyarthritis); and/or other abnormalities. In addition, affected individuals may develop inflammation of arteries that transport blood to heart muscle (coronary arteritis); associated bulging or widening (aneurysms) of the walls of affected coronary arteries; inflammation of heart muscle (myocarditis); and/or other symptoms and findings. Evidence suggests that Kawasaki Disease is the primary cause of acquired heart disease in children in the United States. Some researchers indicate that toxic substances produced by certain forms of bacteria, such as streptococci or staphylococci, may play some role in causing the inflammatory disease process. (For more information on this disorder, choose “Kawasaki” as your search term in the Rare Disease Database.)The Ehrlichioses are rare infectious diseases caused by bacteria in the Ehrlichia family. Three forms of Human Ehrlichial infection have been identified, including Human Granulocytic Ehrlichiosis (HGE), Human Monocytic Ehrlichiosis (HME), and Sennetsu Fever. The bacteria that cause HGE and HME are carried and transmitted by certain ticks. Cases of Sennetsu Fever, which have been limited to Malaysia and Western Japan, are thought to result from ingestion of raw fish. Though caused by different strains of Ehrlichia bacteria, the three disorders are characterized by similar symptoms. Such symptoms may include a sudden high fever, headache, muscle aches (myalgia), chills, a general feeling of ill health (malaise), and fatigue. Some affected individuals may also develop nausea, vomiting, sore throat, cough, diarrhea, loss of appetite, weight loss, and/or other symptoms. Rarely, a skin rash may appear. Laboratory testing may reveal abnormally low numbers of circulating blood platelets (thrombocytopenia), reduced numbers of white blood cells (leukopenia), and increased levels of certain liver enzymes. Without prompt, appropriate treatment, potentially life-threatening complications may occur in some cases. (For further information, choose “Ehrlichiosis” as your search term in the Rare Disease Database.)Leptospirosis is a group of infectious diseases caused by bacterial organisms known as spirochetes (Leptospira), which are transmitted in the urine of certain domestic and wild animals, including dogs, raccoons, and rats. Symptoms may include fever; chills; muscle aches; inflammation of the protective membranes covering the brain (meningitis), with associated headache, stiffness of the neck, and, in some cases, mental changes; and/or other abnormalities. The most severe form of Leptospirosis, known as Weil Syndrome, may also be characterized by reduced blood clotting and associated bleeding within tissues; inflammation of the liver (hepatitis); yellowish discoloration of the skin, mucous membranes, and whites of the eyes (jaundice); kidney (renal) failure; and/or other complications. (For more information on this disorder, choose “Leptospirosis” as your search term in the Rare Disease Database.)Other infectious diseases or inflammatory syndromes may potentially cause certain symptoms and findings similar to those associated with Toxic Shock Syndrome. (For further information, please choose the exact disease name in question as your search term in the Rare Disease Database.)
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Related disorders of Toxic Shock Syndrome. Symptoms of the following disorders may be similar to those of Toxic Shock Syndrome (TSS). Comparisons may be useful for a differential diagnosis:Streptococcal Toxic Shock Syndrome may be characterized by TSS-like symptoms and findings, the sudden onset of shock, and impairment of various organ systems due to infection with certain toxin-secreting strains of streptococcus bacteria (group A beta-hemolytic streptococci). The syndrome, which was initially reported in the mid to late 1980s, may occur in adults or children. The skin and soft tissues are usually the primary sites of infection. Factors that appear to increase the risk of infection may include certain surgical procedures, particular viral infections (e.g., varicella, influenza), and exposure to affected individuals in close environments such as hospitals or nursing homes. Associated symptoms and findings may vary from case to case, depending upon the causative bacterial strain and other factors. Reported features have included initial flu-like symptoms, including fever, chills, muscle aches, and vomiting; low blood pressure (hypotension); confusion; an accelerated heart rate (tachycardia), unusually rapid breathing (tachypnea), and other findings; and sudden onset of shock and multiple organ failure, leading to potentially life-threatening complications.Scarlet Fever is an infectious disease of childhood usually caused by certain toxin-secreting strains of streptococci bacteria (group A beta-hemolytic streptococci). Symptoms may include sore throat, fever, chills, swollen lymph nodes in the neck, a strawberry color to the tongue, and the development of a pinkish-red rash that may be most apparent on the sides of the chest, on the abdomen, and within skin folds. Following resolution of fever, the outer region of previously reddened skin may peel. Other symptoms and findings may also be present.Kawasaki Disease is a rare inflammatory disease of unknown cause that most commonly affects infants and young children. It may be characterized by a sudden fever that lasts for approximately one week or longer; dryness and cracking of the lips; a strawberry-red tongue; swelling of one or more lymph nodes (lymphadenopathy); and/or a reddish skin rash affecting the hands and feet, trunk, and other regions. By about two to three weeks following symptom onset, affected skin tissue may peel (desquamate) from the tips of the fingers and toes, palms of the hands, soles of the feet, and/or other affected areas. Other symptoms and findings may include inflammation and redness of the “whites” of the eyes (bilateral conjunctivitis); irritability; fatigue; inflammation, pain, and swelling of many joints (polyarthritis); and/or other abnormalities. In addition, affected individuals may develop inflammation of arteries that transport blood to heart muscle (coronary arteritis); associated bulging or widening (aneurysms) of the walls of affected coronary arteries; inflammation of heart muscle (myocarditis); and/or other symptoms and findings. Evidence suggests that Kawasaki Disease is the primary cause of acquired heart disease in children in the United States. Some researchers indicate that toxic substances produced by certain forms of bacteria, such as streptococci or staphylococci, may play some role in causing the inflammatory disease process. (For more information on this disorder, choose “Kawasaki” as your search term in the Rare Disease Database.)The Ehrlichioses are rare infectious diseases caused by bacteria in the Ehrlichia family. Three forms of Human Ehrlichial infection have been identified, including Human Granulocytic Ehrlichiosis (HGE), Human Monocytic Ehrlichiosis (HME), and Sennetsu Fever. The bacteria that cause HGE and HME are carried and transmitted by certain ticks. Cases of Sennetsu Fever, which have been limited to Malaysia and Western Japan, are thought to result from ingestion of raw fish. Though caused by different strains of Ehrlichia bacteria, the three disorders are characterized by similar symptoms. Such symptoms may include a sudden high fever, headache, muscle aches (myalgia), chills, a general feeling of ill health (malaise), and fatigue. Some affected individuals may also develop nausea, vomiting, sore throat, cough, diarrhea, loss of appetite, weight loss, and/or other symptoms. Rarely, a skin rash may appear. Laboratory testing may reveal abnormally low numbers of circulating blood platelets (thrombocytopenia), reduced numbers of white blood cells (leukopenia), and increased levels of certain liver enzymes. Without prompt, appropriate treatment, potentially life-threatening complications may occur in some cases. (For further information, choose “Ehrlichiosis” as your search term in the Rare Disease Database.)Leptospirosis is a group of infectious diseases caused by bacterial organisms known as spirochetes (Leptospira), which are transmitted in the urine of certain domestic and wild animals, including dogs, raccoons, and rats. Symptoms may include fever; chills; muscle aches; inflammation of the protective membranes covering the brain (meningitis), with associated headache, stiffness of the neck, and, in some cases, mental changes; and/or other abnormalities. The most severe form of Leptospirosis, known as Weil Syndrome, may also be characterized by reduced blood clotting and associated bleeding within tissues; inflammation of the liver (hepatitis); yellowish discoloration of the skin, mucous membranes, and whites of the eyes (jaundice); kidney (renal) failure; and/or other complications. (For more information on this disorder, choose “Leptospirosis” as your search term in the Rare Disease Database.)Other infectious diseases or inflammatory syndromes may potentially cause certain symptoms and findings similar to those associated with Toxic Shock Syndrome. (For further information, please choose the exact disease name in question as your search term in the Rare Disease Database.)
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Diagnosis of Toxic Shock Syndrome
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The diagnosis of Toxic Shock Syndrome (TSS) has been defined by the Centers for Disease Control clinical and laboratory criteria. TSS is considered probable if three or more criteria are met in association with peeling (desquamation) of affected skin or if five or more criteria are met in the absence of desquamation. The criteria include the following: fever; rash, with possible, subsequent peeling (desquamation), particularly on the palms and soles; low blood pressure (hypotension); the involvement of three or more organ systems (i.e., digestive [gastrointestinal], muscular, mucous membranes, kidneys, liver, blood, and/or brain and spinal cord [central nervous system]). and negative results of blood tests for the infectious diseases Rocky Mountain Spotted Fever, Leptospirosis, and Measles. Sometimes S. aureus may be isolated from the vagina or from localized (focal) wound sites and identified with the use of various laboratory techniques (e.g., bacterial cultures).
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Diagnosis of Toxic Shock Syndrome. The diagnosis of Toxic Shock Syndrome (TSS) has been defined by the Centers for Disease Control clinical and laboratory criteria. TSS is considered probable if three or more criteria are met in association with peeling (desquamation) of affected skin or if five or more criteria are met in the absence of desquamation. The criteria include the following: fever; rash, with possible, subsequent peeling (desquamation), particularly on the palms and soles; low blood pressure (hypotension); the involvement of three or more organ systems (i.e., digestive [gastrointestinal], muscular, mucous membranes, kidneys, liver, blood, and/or brain and spinal cord [central nervous system]). and negative results of blood tests for the infectious diseases Rocky Mountain Spotted Fever, Leptospirosis, and Measles. Sometimes S. aureus may be isolated from the vagina or from localized (focal) wound sites and identified with the use of various laboratory techniques (e.g., bacterial cultures).
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Therapies of Toxic Shock Syndrome
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TreatmentIndividuals with Toxic Shock Syndrome (TSS) should immediately be hospitalized for appropriate intensive treatment. Disease management requires aggressive intravenous fluid and electrolyte replacement and other supportive care measures as appropriate. Vaginal examination is also essential in women to remove a tampon or vaginal contraceptive device and to collect small tissue samples (cultures) from the vagina and neck of the uterus (cervix) for possible isolation of the S. aureus bacterium. In nonmenstrual TSS, measures may include obtaining cultures from and appropriately cleaning and treating focal wound sites.In addition, in individuals with TSS, treatment typically includes the intravenous administration of beta-lactamase resistant antistaphylococcal antibiotics, such as nafcillin or oxacillin, possibly in combination with clindamycin. Other appropriate antibiotic regimens may be required in some cases. Such antibiotic therapy is important in preventing recurrences of TSS. In extremely severe cases, treatment may include infusion of concentrated preparations of certain antibodies (intravenous immune globulins).To prevent menstrual TSS, tampons should only be used intermittently and replaced frequently. Super absorbent brands should also be avoided. Women who use tampons should be aware of the symptoms of TSS and advised to seek immediate medical attention if they occur. In addition, avoidance of tampons is important in helping to prevent a recurrence of menstrual TSS.As noted above (see “Causes”), TSS has also been reported in association with the use of certain vaginal contraceptive devices. Women who use such contraceptive methods are cautioned to carefully follow all package instructions and to share any questions and concerns with their physicians and pharmacists to help minimize risk and ensure proper use.Other treatment for this disorder is symptomatic and supportive.
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Therapies of Toxic Shock Syndrome. TreatmentIndividuals with Toxic Shock Syndrome (TSS) should immediately be hospitalized for appropriate intensive treatment. Disease management requires aggressive intravenous fluid and electrolyte replacement and other supportive care measures as appropriate. Vaginal examination is also essential in women to remove a tampon or vaginal contraceptive device and to collect small tissue samples (cultures) from the vagina and neck of the uterus (cervix) for possible isolation of the S. aureus bacterium. In nonmenstrual TSS, measures may include obtaining cultures from and appropriately cleaning and treating focal wound sites.In addition, in individuals with TSS, treatment typically includes the intravenous administration of beta-lactamase resistant antistaphylococcal antibiotics, such as nafcillin or oxacillin, possibly in combination with clindamycin. Other appropriate antibiotic regimens may be required in some cases. Such antibiotic therapy is important in preventing recurrences of TSS. In extremely severe cases, treatment may include infusion of concentrated preparations of certain antibodies (intravenous immune globulins).To prevent menstrual TSS, tampons should only be used intermittently and replaced frequently. Super absorbent brands should also be avoided. Women who use tampons should be aware of the symptoms of TSS and advised to seek immediate medical attention if they occur. In addition, avoidance of tampons is important in helping to prevent a recurrence of menstrual TSS.As noted above (see “Causes”), TSS has also been reported in association with the use of certain vaginal contraceptive devices. Women who use such contraceptive methods are cautioned to carefully follow all package instructions and to share any questions and concerns with their physicians and pharmacists to help minimize risk and ensure proper use.Other treatment for this disorder is symptomatic and supportive.
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Overview of Tracheobronchomalacia
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SummaryTracheobronchomalacia (TBM) is a condition caused by a weak airway that collapses when the patient breathes. It can present either at birth or in adulthood with a cough, shortness of breath and/or recurrent infections. TBM occurs when the walls of the airway (specifically the trachea and bronchi) are weak. As the patient breathes out, the weak airway collapses partially or completely. There are two forms of TBM: primary (congenital) and secondary (acquired). Primary TBM typically presents at birth or during infancy due to a malformed airway. Secondary TBM is an acquired form usually seen in adults with weakened airways. Symptoms include shortness of breath, a “barking” cough, chronic airway infections, and/or wheezing or stridor with breathing. These symptoms may mimic other diseases or not be present at all, which makes TBM more difficult to diagnose and likely less rare than previously thought. A pulmonologist confirms the diagnosis and severity with a flexible bronchoscopy. Case severity may vary widely, but prognosis has continually improved with supportive measures. IntroductionPrimary tracheobronchomalacia is caused by congenital conditions that weaken or compress the walls of the airway (i.e. tracheoesophageal fistula, esophageal atresia, or Ehlers-Danlos syndrome). Secondary or acquired TBM may occur due to trauma (i.e. prolonged intubation or trachea surgery) and is always associated with another condition (i.e. COPD, asthma, chronic infections, heartburn, and sleep apnea). The exact mechanism causing TBM is largely unknown. Treatment may only be needed if signs and symptoms are present and affecting the patient’s quality of life. Depending on severity, treatment options may include continuous positive airway pressure (CPAP), stenting, or tracheobronchoplasty.
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Overview of Tracheobronchomalacia. SummaryTracheobronchomalacia (TBM) is a condition caused by a weak airway that collapses when the patient breathes. It can present either at birth or in adulthood with a cough, shortness of breath and/or recurrent infections. TBM occurs when the walls of the airway (specifically the trachea and bronchi) are weak. As the patient breathes out, the weak airway collapses partially or completely. There are two forms of TBM: primary (congenital) and secondary (acquired). Primary TBM typically presents at birth or during infancy due to a malformed airway. Secondary TBM is an acquired form usually seen in adults with weakened airways. Symptoms include shortness of breath, a “barking” cough, chronic airway infections, and/or wheezing or stridor with breathing. These symptoms may mimic other diseases or not be present at all, which makes TBM more difficult to diagnose and likely less rare than previously thought. A pulmonologist confirms the diagnosis and severity with a flexible bronchoscopy. Case severity may vary widely, but prognosis has continually improved with supportive measures. IntroductionPrimary tracheobronchomalacia is caused by congenital conditions that weaken or compress the walls of the airway (i.e. tracheoesophageal fistula, esophageal atresia, or Ehlers-Danlos syndrome). Secondary or acquired TBM may occur due to trauma (i.e. prolonged intubation or trachea surgery) and is always associated with another condition (i.e. COPD, asthma, chronic infections, heartburn, and sleep apnea). The exact mechanism causing TBM is largely unknown. Treatment may only be needed if signs and symptoms are present and affecting the patient’s quality of life. Depending on severity, treatment options may include continuous positive airway pressure (CPAP), stenting, or tracheobronchoplasty.
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Symptoms of Tracheobronchomalacia
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Many patients with TBM are asymptomatic. The most common symptoms include:Adults with secondary TBM will have symptoms that progressively get worse over time.
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Symptoms of Tracheobronchomalacia. Many patients with TBM are asymptomatic. The most common symptoms include:Adults with secondary TBM will have symptoms that progressively get worse over time.
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Causes of Tracheobronchomalacia
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Primary TBM (present at birth) can be due to:Causes of acquired TBM which presents in adulthood are often unknown but may be associated with:These conditions can cause the breakdown of the cartilage that holds open the airway, resulting in tracheobronchomalacia.
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Causes of Tracheobronchomalacia. Primary TBM (present at birth) can be due to:Causes of acquired TBM which presents in adulthood are often unknown but may be associated with:These conditions can cause the breakdown of the cartilage that holds open the airway, resulting in tracheobronchomalacia.
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Affects of Tracheobronchomalacia
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Primary TBM is a relatively uncommon condition, estimated to occur in 1 in 1,445-2,100 livebirths. The genetic factors associated with primary TBM are unknown. However, primary tracheobronchomalacia is often associated with certain genetic conditions or structural birth defects, particularly tracheoesophageal fistula and esophageal atresia.Secondary TBM is not inherited. It occurs in patients with underlying conditions or exposures that weaken the cartilage in the airway (see Causes).
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Affects of Tracheobronchomalacia. Primary TBM is a relatively uncommon condition, estimated to occur in 1 in 1,445-2,100 livebirths. The genetic factors associated with primary TBM are unknown. However, primary tracheobronchomalacia is often associated with certain genetic conditions or structural birth defects, particularly tracheoesophageal fistula and esophageal atresia.Secondary TBM is not inherited. It occurs in patients with underlying conditions or exposures that weaken the cartilage in the airway (see Causes).
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Related disorders of Tracheobronchomalacia
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Tracheomalacia – the cartilage of the trachea alone is weakened, causing it to collapse when exhalingBronchomalacia – the cartilage of the bronchus alone is weakened, causing it to collapse when exhalingExcessive dynamic airway collapse (EDAC) – the airway cartilage is normal, but the posterior wall is excessively mobile, causing the trachea to collapse when exhalingCongenital vascular disorders – these include any malformed blood vessels which compress the windpipe and weaken it, including vascular rings, innominate arteries and double aortic archesTracheoesophageal fistula – a rare birth defect where the esophagus forms incorrectly and connects to the windpipe rather than the stomach. Infants will have trouble breathing and swallowing and require surgery.
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Related disorders of Tracheobronchomalacia. Tracheomalacia – the cartilage of the trachea alone is weakened, causing it to collapse when exhalingBronchomalacia – the cartilage of the bronchus alone is weakened, causing it to collapse when exhalingExcessive dynamic airway collapse (EDAC) – the airway cartilage is normal, but the posterior wall is excessively mobile, causing the trachea to collapse when exhalingCongenital vascular disorders – these include any malformed blood vessels which compress the windpipe and weaken it, including vascular rings, innominate arteries and double aortic archesTracheoesophageal fistula – a rare birth defect where the esophagus forms incorrectly and connects to the windpipe rather than the stomach. Infants will have trouble breathing and swallowing and require surgery.
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Diagnosis of Tracheobronchomalacia
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A dynamic CT scan and flexible bronchoscopy can confirm the diagnosis and evaluate the severity of the condition. The patient is awake but numbed during the flexible bronchoscopy and asked to take deep breaths or cough. TBM is considered mild if the trachea narrows to 50% of its initial size as the patient is breathing out, moderate if it narrows to 25%, and severe if the walls of the trachea touch.Clinical Testing and Work-upThe presenting symptoms of shortness of breath, a “barking” cough, and chronic infections may first raise suspicion for TBM. The next step is often to obtain pulmonary function tests which are abnormal. To make the diagnosis and determine the severity, a physician will likely order a chest CT scan and bronchoscopy. These tests are important to rule out other conditions such as asthma, a foreign body and pneumonia. To determine the proper treatment, the doctor will investigate possible underlying issues causing the disease.
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Diagnosis of Tracheobronchomalacia. A dynamic CT scan and flexible bronchoscopy can confirm the diagnosis and evaluate the severity of the condition. The patient is awake but numbed during the flexible bronchoscopy and asked to take deep breaths or cough. TBM is considered mild if the trachea narrows to 50% of its initial size as the patient is breathing out, moderate if it narrows to 25%, and severe if the walls of the trachea touch.Clinical Testing and Work-upThe presenting symptoms of shortness of breath, a “barking” cough, and chronic infections may first raise suspicion for TBM. The next step is often to obtain pulmonary function tests which are abnormal. To make the diagnosis and determine the severity, a physician will likely order a chest CT scan and bronchoscopy. These tests are important to rule out other conditions such as asthma, a foreign body and pneumonia. To determine the proper treatment, the doctor will investigate possible underlying issues causing the disease.
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Therapies of Tracheobronchomalacia
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Before pursuing surgery, the treatment team will try treating the underlying cause, if one is present. Chronic infections and traumas should be treated first, if possible. If the cause of the TBM is genetic or cannot be corrected with medical therapies, other avenues will be explored. Patients may receive continuous positive airway pressure (CPAP), a machine often used for obstructive sleep apnea that pushes air into the lungs to keep them inflated. A silicone stent may be inserted to hold open the airway. More severe cases require surgical correction of the weakened airway (see Treatment).Treatment
TBM is managed by a team of specialists working together, which includes interventional pulmonologists, respiratory therapists, radiologists, and surgeons. Treatment may only be needed if signs and symptoms are present, quality of life is impaired, and/or there is complete or near-complete collapse of the airway. Age and other conditions that a patient has may also be factors that the treatment team considers in deciding about advanced treatment. Initial management of symptoms may depend on whether an underlying condition is contributing to symptoms, and whether that condition can be managed. In some patients, treating the underlying condition improves the symptoms of TBM. Depending on severity, treatment options for TBM that continues to progress may include:Even with treatment, continued surveillance is recommended to identify any progression or recurrence of symptoms.
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Therapies of Tracheobronchomalacia. Before pursuing surgery, the treatment team will try treating the underlying cause, if one is present. Chronic infections and traumas should be treated first, if possible. If the cause of the TBM is genetic or cannot be corrected with medical therapies, other avenues will be explored. Patients may receive continuous positive airway pressure (CPAP), a machine often used for obstructive sleep apnea that pushes air into the lungs to keep them inflated. A silicone stent may be inserted to hold open the airway. More severe cases require surgical correction of the weakened airway (see Treatment).Treatment
TBM is managed by a team of specialists working together, which includes interventional pulmonologists, respiratory therapists, radiologists, and surgeons. Treatment may only be needed if signs and symptoms are present, quality of life is impaired, and/or there is complete or near-complete collapse of the airway. Age and other conditions that a patient has may also be factors that the treatment team considers in deciding about advanced treatment. Initial management of symptoms may depend on whether an underlying condition is contributing to symptoms, and whether that condition can be managed. In some patients, treating the underlying condition improves the symptoms of TBM. Depending on severity, treatment options for TBM that continues to progress may include:Even with treatment, continued surveillance is recommended to identify any progression or recurrence of symptoms.
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Overview of Transverse Myelitis
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Summary
Transverse myelitis (TM) is a rare inflammatory disease-causing injury to the spinal cord with varying degrees of weakness, sensory alterations and autonomic dysfunction (the part of the nervous system that controls important involuntary functions such as the heart, blood pressure, bladder, the digestive system, sexual functions. etc.)IntroductionThe first cases of acute myelitis were described in 1882 and were attributed to vascular lesions and acute inflammatory events. In England between 1922 and 1923 more than 200 post-vaccinal cases were noted as complications of the smallpox and rabies vaccines. Later reports revealed that TM was post-infectious in nature, and agents including measles, rubella and mycoplasma were directly isolated from the patient’s spinal fluid. The term “acute transverse myelitis” was first used by an English neurologist in 1948 to describe a case of rapidly progressive paraparesis with a thoracic sensory level, occurring as a postinfectious complication of pneumonia. The Transverse Myelitis Consortium Working Group delineated diagnostic criteria for disease-associated TM and idiopathic TM along with a framework to differentiate TM from non-inflammatory myelopathies in 2002.
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Overview of Transverse Myelitis. Summary
Transverse myelitis (TM) is a rare inflammatory disease-causing injury to the spinal cord with varying degrees of weakness, sensory alterations and autonomic dysfunction (the part of the nervous system that controls important involuntary functions such as the heart, blood pressure, bladder, the digestive system, sexual functions. etc.)IntroductionThe first cases of acute myelitis were described in 1882 and were attributed to vascular lesions and acute inflammatory events. In England between 1922 and 1923 more than 200 post-vaccinal cases were noted as complications of the smallpox and rabies vaccines. Later reports revealed that TM was post-infectious in nature, and agents including measles, rubella and mycoplasma were directly isolated from the patient’s spinal fluid. The term “acute transverse myelitis” was first used by an English neurologist in 1948 to describe a case of rapidly progressive paraparesis with a thoracic sensory level, occurring as a postinfectious complication of pneumonia. The Transverse Myelitis Consortium Working Group delineated diagnostic criteria for disease-associated TM and idiopathic TM along with a framework to differentiate TM from non-inflammatory myelopathies in 2002.
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Symptoms of Transverse Myelitis
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The spinal cord carries motor nerve fibers to the limbs and trunk and sensory fibers from the body back to the brain. Inflammation within the spinal cord interrupts these pathways and causes the typical presenting symptoms. TM generally presents with rapidly progressing muscle weakness or paralysis, beginning with the legs and potentially moving to the arms with varying degrees of severity. The arm involvement is dependent upon the level of spinal cord affected. Sensation to light touch is diminished below the level of spinal cord lesion in most individuals. Pain (ascertained as appreciation of pinprick by the neurologist) and temperature sensation are generally diminished and appreciation of vibration (as tested by a tuning fork) and joint position sense may also be decreased. Many patients report a tight banding or girdle-like sensation around the trunk and that area may be very sensitive to touch.In most patients a sensory level is documented, most commonly in the mid-thoracic region in adults or the cervical region in children. Pain in the back (that might suggest where the inflammation is localized), extremities, or abdomen, as well as tingling, numbness, burning sensations are common. Increased urinary urgency, frequency, hesitancy to start voiding, interrupted urine stream, incomplete bladder emptying or inability to void, or urinary incontinence, as well as incomplete evacuation of bowel or constipation or bowel incontinence, are other characteristic autonomic symptoms. Spasticity and fatigue are other symptoms common to TM. Sexual dysfunction is also the result of sensory and autonomic involvement, but also may be contributed by depression that sometimes accompanies TM. In some patients, symptoms progress over hours whereas in other instances, the presentation is over days. Neurologic function tends to decline during the 4h-21-day acute phase, while eighty percent of patients reach their maximal deficit within 10 days of symptom onset. At its worst point, 50% of individuals have lost all movements of their legs, 80-94% experience numbness, tingling or pain, the feeling of “banding or girdling”, and almost all have some degree of bladder dysfunction.Recovery from TM may be absent, partial or complete and generally begins within 1 to 3 months after acute treatment. Significant recovery is unlikely if no improvement occurs by 3 months. After the initial attack, approximately 1/3 of individuals recover with little or only minor symptoms, 1/3 are left with a moderate degree of permanent disability and 1/3 have virtually no recovery and are left severely functionally disabled. Most show good to fair recovery. The rapid progression of clinical symptoms, the presence of back pain, and the presence of spinal shock, as well as para-clinical evidence, such as absent central motor conduction response on evoked potential testing and the presence of elevated 14-3-3 protein in the cerebrospinal fluid (CSF) during the acute phase, might be indicators of a less complete recovery. It is important to know that the neurological outcome in patients with TM cannot be predicted based on imaging findings.TM usually occurs only once, but in a subset of patients TM can be recurrent. Recurrence can often be predicted at the initial acute onset based on multifocal lesions in the spinal cord, lesions in the brain, presence of an underlying mixed connective tissue disease, the presence of oligoclonal bands in the CSF, and/or NMO-IgG, as well as persistence of MOG-IgG antibodies over time.
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Symptoms of Transverse Myelitis. The spinal cord carries motor nerve fibers to the limbs and trunk and sensory fibers from the body back to the brain. Inflammation within the spinal cord interrupts these pathways and causes the typical presenting symptoms. TM generally presents with rapidly progressing muscle weakness or paralysis, beginning with the legs and potentially moving to the arms with varying degrees of severity. The arm involvement is dependent upon the level of spinal cord affected. Sensation to light touch is diminished below the level of spinal cord lesion in most individuals. Pain (ascertained as appreciation of pinprick by the neurologist) and temperature sensation are generally diminished and appreciation of vibration (as tested by a tuning fork) and joint position sense may also be decreased. Many patients report a tight banding or girdle-like sensation around the trunk and that area may be very sensitive to touch.In most patients a sensory level is documented, most commonly in the mid-thoracic region in adults or the cervical region in children. Pain in the back (that might suggest where the inflammation is localized), extremities, or abdomen, as well as tingling, numbness, burning sensations are common. Increased urinary urgency, frequency, hesitancy to start voiding, interrupted urine stream, incomplete bladder emptying or inability to void, or urinary incontinence, as well as incomplete evacuation of bowel or constipation or bowel incontinence, are other characteristic autonomic symptoms. Spasticity and fatigue are other symptoms common to TM. Sexual dysfunction is also the result of sensory and autonomic involvement, but also may be contributed by depression that sometimes accompanies TM. In some patients, symptoms progress over hours whereas in other instances, the presentation is over days. Neurologic function tends to decline during the 4h-21-day acute phase, while eighty percent of patients reach their maximal deficit within 10 days of symptom onset. At its worst point, 50% of individuals have lost all movements of their legs, 80-94% experience numbness, tingling or pain, the feeling of “banding or girdling”, and almost all have some degree of bladder dysfunction.Recovery from TM may be absent, partial or complete and generally begins within 1 to 3 months after acute treatment. Significant recovery is unlikely if no improvement occurs by 3 months. After the initial attack, approximately 1/3 of individuals recover with little or only minor symptoms, 1/3 are left with a moderate degree of permanent disability and 1/3 have virtually no recovery and are left severely functionally disabled. Most show good to fair recovery. The rapid progression of clinical symptoms, the presence of back pain, and the presence of spinal shock, as well as para-clinical evidence, such as absent central motor conduction response on evoked potential testing and the presence of elevated 14-3-3 protein in the cerebrospinal fluid (CSF) during the acute phase, might be indicators of a less complete recovery. It is important to know that the neurological outcome in patients with TM cannot be predicted based on imaging findings.TM usually occurs only once, but in a subset of patients TM can be recurrent. Recurrence can often be predicted at the initial acute onset based on multifocal lesions in the spinal cord, lesions in the brain, presence of an underlying mixed connective tissue disease, the presence of oligoclonal bands in the CSF, and/or NMO-IgG, as well as persistence of MOG-IgG antibodies over time.
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Causes of Transverse Myelitis
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The possible causes of TM can be quite varied. TM may occur in isolation or in the setting of another illness. Idiopathic TM is assumed to be a result of abnormal and excessive activation of an immune response against the spinal cord that results in inflammation and tissue damage (for which the exact cause is still undetermined).TM can be the presenting feature of MS. In individuals with acute partial TM and normal brain MRI, about 10-33 percent develop MS over a five to ten-year period. If the brain MRI shows lesions, the transition rate to clinically definite MS is known to be quite high, in the range of 80 to 90 percent within a few years. Those who are ultimately diagnosed with MS are more likely to have asymmetric clinical findings, predominant sensory symptoms with relative sparing of motor systems, MR lesions extending over fewer than 2 spinal segments, abnormal brain MRI and oligoclonal bands in the CSF.TM can often be seen in patients who test positive for NMO-IgG (an autoantibody that is a highly specific biomarker for the immune-mediated disease called neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), as well as in patients who test positive for MOG-IgG (another autoimmune antibody marker for MOGAD (myelin oligodendrocyte glycoprotein antibody associated disease, a disease recently distinguished from NMO/NMOSD). In patients with those conditions myelitis symptoms are frequently symmetrical (opposite to MS where myelitis symptoms are typically asymmetrical). In patients with NMO/NMOSD myelitis most frequently affects at least 3 spinal segments (and therefore is called longitudinally extensive TM), however about 1/3 of patients with NMO/NMOSD can have lesions in the spinal cord that are affecting less than 3 spinal segments on MRI imaging. TM often develops in the setting of viral and bacterial infections, especially those which may be associated with a rash (e.g., rubeola, varicella, variola, rubella, influenza and mumps). The term parainfectious suggests that the neurologic injury associated with TM may be related to direct microbial infection and injury as a result of the infection, microbial infection with immune-mediated systemic response that induces neural injury. Cases of TM in association with COVID19 infection have also been reported. Approximately one third of individuals with TM report a febrile illness (flu-like illness with fever) in close temporal relationship to the onset of neurologic symptoms. In some cases, there is evidence that there is a direct invasion and injury to the cord by the infectious agent itself (especially poliomyelitis, herpes zoster, AIDS and Lyme neuroborreliosis). However, causality may not always be established. A bacterial abscess can also develop around the spinal cord and injure the cord through compression, bacterial invasion and inflammation. Fungal and parasitic infections can also cause TM. Experts believe that in many patients, infection causes a derangement of the immune system, which leads to an autoimmune attack on the spinal cord, rather than a direct attack by the organism. One theory to explain this abnormal activation of the immune system toward human tissue is termed molecular mimicry. This theory is that an infectious agent may share a molecule that resembles or mimics a molecule in the spinal cord. When the body mounts an immune response to the invading virus or bacterium, it also responds to the spinal cord molecule with which it shares structural characteristics. This leads to inflammation and injury within the spinal cord.Although a causal relationship has not been established, TM has been anecdotally reported following vaccinations against rabies, diphtheria-tetanus-polio, pertussis, MMR, influenza and hepatitis B. Recently, several cases of TM have been reported following COVID19 vaccination. One theory suggests that it is possible that the vaccination may have excited an autoimmune process. It is critically important to bear in mind that extensive research has demonstrated that vaccinations are safe, and the potential link to TM may only be coincidental or at worst is an exceptionally rare complication, and that benefits of receiving the vaccines exceed the low risk of vaccine complications. Myelitis related to cancer (called paraneoplastic syndrome) is uncommon. There are several reports in the medical literature of a myelitis occurring in association with a malignancy, in which the immune system produces an antibody or immune cells to fight off the cancer and this cross-reacts with the molecules in the spinal cord neurons, leading to spinal cord inflammation. Vascular causes are noted because they present with the same problems as TM. However, this is really a distinct problem primarily due to inadequate blood flow to the spinal cord instead of actual spinal cord inflammation. The blood vessels to the spinal cord can close up with blood clots or atherosclerosis or burst and bleed. This is essentially a “stroke” of the spinal cord.
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Causes of Transverse Myelitis. The possible causes of TM can be quite varied. TM may occur in isolation or in the setting of another illness. Idiopathic TM is assumed to be a result of abnormal and excessive activation of an immune response against the spinal cord that results in inflammation and tissue damage (for which the exact cause is still undetermined).TM can be the presenting feature of MS. In individuals with acute partial TM and normal brain MRI, about 10-33 percent develop MS over a five to ten-year period. If the brain MRI shows lesions, the transition rate to clinically definite MS is known to be quite high, in the range of 80 to 90 percent within a few years. Those who are ultimately diagnosed with MS are more likely to have asymmetric clinical findings, predominant sensory symptoms with relative sparing of motor systems, MR lesions extending over fewer than 2 spinal segments, abnormal brain MRI and oligoclonal bands in the CSF.TM can often be seen in patients who test positive for NMO-IgG (an autoantibody that is a highly specific biomarker for the immune-mediated disease called neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), as well as in patients who test positive for MOG-IgG (another autoimmune antibody marker for MOGAD (myelin oligodendrocyte glycoprotein antibody associated disease, a disease recently distinguished from NMO/NMOSD). In patients with those conditions myelitis symptoms are frequently symmetrical (opposite to MS where myelitis symptoms are typically asymmetrical). In patients with NMO/NMOSD myelitis most frequently affects at least 3 spinal segments (and therefore is called longitudinally extensive TM), however about 1/3 of patients with NMO/NMOSD can have lesions in the spinal cord that are affecting less than 3 spinal segments on MRI imaging. TM often develops in the setting of viral and bacterial infections, especially those which may be associated with a rash (e.g., rubeola, varicella, variola, rubella, influenza and mumps). The term parainfectious suggests that the neurologic injury associated with TM may be related to direct microbial infection and injury as a result of the infection, microbial infection with immune-mediated systemic response that induces neural injury. Cases of TM in association with COVID19 infection have also been reported. Approximately one third of individuals with TM report a febrile illness (flu-like illness with fever) in close temporal relationship to the onset of neurologic symptoms. In some cases, there is evidence that there is a direct invasion and injury to the cord by the infectious agent itself (especially poliomyelitis, herpes zoster, AIDS and Lyme neuroborreliosis). However, causality may not always be established. A bacterial abscess can also develop around the spinal cord and injure the cord through compression, bacterial invasion and inflammation. Fungal and parasitic infections can also cause TM. Experts believe that in many patients, infection causes a derangement of the immune system, which leads to an autoimmune attack on the spinal cord, rather than a direct attack by the organism. One theory to explain this abnormal activation of the immune system toward human tissue is termed molecular mimicry. This theory is that an infectious agent may share a molecule that resembles or mimics a molecule in the spinal cord. When the body mounts an immune response to the invading virus or bacterium, it also responds to the spinal cord molecule with which it shares structural characteristics. This leads to inflammation and injury within the spinal cord.Although a causal relationship has not been established, TM has been anecdotally reported following vaccinations against rabies, diphtheria-tetanus-polio, pertussis, MMR, influenza and hepatitis B. Recently, several cases of TM have been reported following COVID19 vaccination. One theory suggests that it is possible that the vaccination may have excited an autoimmune process. It is critically important to bear in mind that extensive research has demonstrated that vaccinations are safe, and the potential link to TM may only be coincidental or at worst is an exceptionally rare complication, and that benefits of receiving the vaccines exceed the low risk of vaccine complications. Myelitis related to cancer (called paraneoplastic syndrome) is uncommon. There are several reports in the medical literature of a myelitis occurring in association with a malignancy, in which the immune system produces an antibody or immune cells to fight off the cancer and this cross-reacts with the molecules in the spinal cord neurons, leading to spinal cord inflammation. Vascular causes are noted because they present with the same problems as TM. However, this is really a distinct problem primarily due to inadequate blood flow to the spinal cord instead of actual spinal cord inflammation. The blood vessels to the spinal cord can close up with blood clots or atherosclerosis or burst and bleed. This is essentially a “stroke” of the spinal cord.
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Affects of Transverse Myelitis
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TM has a conservatively estimated incidence of between 1 and 8 new cases per million per year, or approximately 1,400 new cases each year. However, this is probably an underestimate. Although this disease affects people of all ages, with a range of six months to 88 years, there are peaks between the ages of 10 to 19 years and 30 to 39 years. In addition, approximately 25% of cases are in children. There is no gender or familial association with TM. In 75-90% of cases TM occurs only once, yet a small percentage of patients have recurrent disease especially if there is a predisposing underlying illness.
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Affects of Transverse Myelitis. TM has a conservatively estimated incidence of between 1 and 8 new cases per million per year, or approximately 1,400 new cases each year. However, this is probably an underestimate. Although this disease affects people of all ages, with a range of six months to 88 years, there are peaks between the ages of 10 to 19 years and 30 to 39 years. In addition, approximately 25% of cases are in children. There is no gender or familial association with TM. In 75-90% of cases TM occurs only once, yet a small percentage of patients have recurrent disease especially if there is a predisposing underlying illness.
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Related disorders of Transverse Myelitis
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As mentioned above, TM may be a relatively uncommon manifestation of several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren’s syndrome and sarcoidosis. SLE is an autoimmune disease of unknown cause that affects multiple organs and tissues in the body. SLE may cause TM that may even be recurrent. Sjogren’s disease is another autoimmune disease characterized by invasion and infiltration of the tear and salivary glands by white blood cells with resultant decreased production of these fluids leading to dry mouth and dry eyes. Several tests can support this diagnosis: the presence of a SS-A/SS-B antibody in the blood, ophthalmologic tests that confirm decreased tear production and the demonstration of lymphocytic infiltration in biopsy specimens of the small salivary glands (a minimally invasive procedure). Neurologic manifestations are unusual in Sjogren’s syndrome, and spinal cord inflammation can occur. Sarcoidosis is a multisystem inflammatory disorder of unknown cause and manifested by enlarged lymph nodes, lung inflammation, various skin lesions, liver and other organ involvement. In the nervous system, various nerves, as well as the spinal cord, may be involved. Diagnosis is generally confirmed by biopsy, demonstrating features of inflammation typical of sarcoidosis. (For more information on these disorders, search for the condition in the Rare Disease Database.)
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Related disorders of Transverse Myelitis. As mentioned above, TM may be a relatively uncommon manifestation of several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren’s syndrome and sarcoidosis. SLE is an autoimmune disease of unknown cause that affects multiple organs and tissues in the body. SLE may cause TM that may even be recurrent. Sjogren’s disease is another autoimmune disease characterized by invasion and infiltration of the tear and salivary glands by white blood cells with resultant decreased production of these fluids leading to dry mouth and dry eyes. Several tests can support this diagnosis: the presence of a SS-A/SS-B antibody in the blood, ophthalmologic tests that confirm decreased tear production and the demonstration of lymphocytic infiltration in biopsy specimens of the small salivary glands (a minimally invasive procedure). Neurologic manifestations are unusual in Sjogren’s syndrome, and spinal cord inflammation can occur. Sarcoidosis is a multisystem inflammatory disorder of unknown cause and manifested by enlarged lymph nodes, lung inflammation, various skin lesions, liver and other organ involvement. In the nervous system, various nerves, as well as the spinal cord, may be involved. Diagnosis is generally confirmed by biopsy, demonstrating features of inflammation typical of sarcoidosis. (For more information on these disorders, search for the condition in the Rare Disease Database.)
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Diagnosis of Transverse Myelitis
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Diagnosis of TM is based on clinical and radiological findings. Clinical characteristics of myelopathy are signs and/or symptoms of sensory, motor or autonomic dysfunction attributable to the spinal cord. Evidence of inflammation either on MRI as gadolinium enhancement or on lumbar puncture as elevated CSF white blood cells, or the presence of oligoclonal IgG bands unique to the CSF or elevated IgG index, are frequently observed.If a myelopathy is suspected based on history and physical examination, a gadolinium-enhanced MRI of the spinal cord is first obtained to assess if there is a compressive or inflammatory (gadolinium enhancing) lesion, or a spinal cord stroke, as signs and symptoms may be alike. It is essential to rule out compressive myelopathy (compression of the spinal cord), which can be caused by a tumor, herniated disc, hematoma or abscess. Identifying these disorders is critical since immobilization to prevent further injury and early surgery to remove the compression may sometimes reverse neurologic injury to the spinal cord.Lumbar puncture is used to look for surrogate markers for inflammation in the CSF. These include elevated CSF white cell counts, elevated CSF protein and an elevated IgG index/or the presence of oligoclonal IgG bands unique to the CSF. It should be noted, however, that a significant percentage of individuals with a clinical pattern that otherwise resembles TM do not meet these inflammatory features and, therefore, the absence of inflammatory markers does not rule out TM.To identify the underlying cause of the inflammatory process, specific tests are recommended to assess for the presence of a systemic inflammatory disease – such as Sjögren’s syndrome, lupus (SLE) and neurosarcoidosis, and some others. It is important to test for vitamin B12 and copper levels. NMO-IgG and MOG-IgG tests should be ordered. If there is a suspicion of paraneoplastic myelitis- appropriate antibody panels in serum and CSF should be done. Infections need to be ruled out.A MRI of the brain is performed to screen for lesions suggestive of MS or other diseases (NMO/NMOSD, acute disseminated encephalomyelitis, neuro-lupus, neuro- Sjogren’s syndrome, neurosarcoidosis) that may affect the brain in addition to the spinal cord. If no clear cause can be identified, the diagnosis is idiopathic TM.Non-inflammatory myelopathies include those caused by arterial or venous ischemia (blockage), vascular malformations, radiation, or nutritional/metabolic causes and appropriate workups under these situations might include aortic ultrasound, spinal angiogram or evaluation of pro-thrombotic risk factors.Within the category of idiopathic TM, it may be of further value to distinguish between acute partial TM, acute complete TM and longitudinally extensive TM (LETM), since these syndromes present distinct differential diagnoses and prognoses.Acute partial transverse myelitis refers to usually mild and asymmetrical spinal cord dysfunction with a MRI lesion of less than 3 vertebral segments. Acute complete TM refers to a complete or near complete clinical deficit below the lesion and an MRI lesion of less than 3 vertebral segments. LETM has a complete or incomplete clinical picture, but an MRI lesion that is longer than or equal to 3 vertebral segments.
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Diagnosis of Transverse Myelitis. Diagnosis of TM is based on clinical and radiological findings. Clinical characteristics of myelopathy are signs and/or symptoms of sensory, motor or autonomic dysfunction attributable to the spinal cord. Evidence of inflammation either on MRI as gadolinium enhancement or on lumbar puncture as elevated CSF white blood cells, or the presence of oligoclonal IgG bands unique to the CSF or elevated IgG index, are frequently observed.If a myelopathy is suspected based on history and physical examination, a gadolinium-enhanced MRI of the spinal cord is first obtained to assess if there is a compressive or inflammatory (gadolinium enhancing) lesion, or a spinal cord stroke, as signs and symptoms may be alike. It is essential to rule out compressive myelopathy (compression of the spinal cord), which can be caused by a tumor, herniated disc, hematoma or abscess. Identifying these disorders is critical since immobilization to prevent further injury and early surgery to remove the compression may sometimes reverse neurologic injury to the spinal cord.Lumbar puncture is used to look for surrogate markers for inflammation in the CSF. These include elevated CSF white cell counts, elevated CSF protein and an elevated IgG index/or the presence of oligoclonal IgG bands unique to the CSF. It should be noted, however, that a significant percentage of individuals with a clinical pattern that otherwise resembles TM do not meet these inflammatory features and, therefore, the absence of inflammatory markers does not rule out TM.To identify the underlying cause of the inflammatory process, specific tests are recommended to assess for the presence of a systemic inflammatory disease – such as Sjögren’s syndrome, lupus (SLE) and neurosarcoidosis, and some others. It is important to test for vitamin B12 and copper levels. NMO-IgG and MOG-IgG tests should be ordered. If there is a suspicion of paraneoplastic myelitis- appropriate antibody panels in serum and CSF should be done. Infections need to be ruled out.A MRI of the brain is performed to screen for lesions suggestive of MS or other diseases (NMO/NMOSD, acute disseminated encephalomyelitis, neuro-lupus, neuro- Sjogren’s syndrome, neurosarcoidosis) that may affect the brain in addition to the spinal cord. If no clear cause can be identified, the diagnosis is idiopathic TM.Non-inflammatory myelopathies include those caused by arterial or venous ischemia (blockage), vascular malformations, radiation, or nutritional/metabolic causes and appropriate workups under these situations might include aortic ultrasound, spinal angiogram or evaluation of pro-thrombotic risk factors.Within the category of idiopathic TM, it may be of further value to distinguish between acute partial TM, acute complete TM and longitudinally extensive TM (LETM), since these syndromes present distinct differential diagnoses and prognoses.Acute partial transverse myelitis refers to usually mild and asymmetrical spinal cord dysfunction with a MRI lesion of less than 3 vertebral segments. Acute complete TM refers to a complete or near complete clinical deficit below the lesion and an MRI lesion of less than 3 vertebral segments. LETM has a complete or incomplete clinical picture, but an MRI lesion that is longer than or equal to 3 vertebral segments.
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Therapies of Transverse Myelitis
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Intravenous Steroids
Intravenous steroid treatment is the first line of therapy often used in acute TM. Corticosteroids have multiple mechanisms of action including anti-inflammatory activity, immunosuppressive properties and antiproliferative actions. Though there is no randomized double-blind placebo-controlled study that supports this approach, evidence from related disorders and clinical experience support this treatment. At the Johns Hopkins TM Center, the standard of care includes intravenous methylprednisolone (1000 mg) or dexamethasone (200 mg) for 3 to 5 days unless there are compelling reasons to avoid this therapy. However, high dose steroid treatment intravenously may be given for 3-7 days. The decision to offer continued steroids or to add a new treatment is often based on the clinical course, the underlying cause and MRI appearance at the end of high dose steroid course. Plasma Exchange (PLEX)
PLEX is often initiated in moderate to severe TM (i.e., inability to walk, markedly impaired autonomic function, and sensory loss in the lower extremities) in individuals who show little clinical improvement after instituting 5 to 7 days of intravenous steroids but may also be initiated at first presentation. PLEX is believed to work in autoimmune CNS diseases through the removal of specific or nonspecific soluble factors likely to mediate, be responsible for, or contribute to inflammatory-mediated target organ damage. PLEX has been shown to be effective in adults with TM and other acute inflammatory disorders of the CNS.Other Immunomodulatory Treatment
If there is continued progression despite intravenous steroid therapy and PLEX, pulse dose intravenous cyclophosphamide (750-1000 mg/m2) is considered. Cyclophosphamide is known to have immunosuppressive properties. From the Johns Hopkins TM Center experience, it has been reported that PLEX provided an added benefit to steroids in patients who were not at a disability level of ASIA A at nadir and who did not have a history of autoimmune disease. For those who were classified at a disability level of ASIA A at their nadir, they showed a significant benefit when given combination therapy with steroids, PLEX and IV cyclophosphamide. Cyclophosphamide should be administered under the supervision of an experienced oncology team, and caregivers should monitor the patient carefully for hemorrhagic cystitis and cytopenia.Chronic immunomodulatory therapy should be considered for recurrent TM. The ideal treatment regimen is not known, and it is important for your neurologist to consult with a specialist who has significant experience in treating these rare, recurrent neuroimmunologic disorders.Long-term Care and Management
After the acute phase, rehabilitative care to improve functional skills and prevent secondary complications of immobility involves both psychological and physical accommodations. There is very little written in the medical literature specifically dealing with rehabilitation after transverse myelitis. However, much has been written regarding recovery from spinal cord injury (SCI) in general, and this literature applies. The physical issues include bowel and bladder management, sexuality, maintenance of skin integrity, spasticity, activities of daily living (i.e., dressing), mobility, and pain.It is important to begin occupational and physical therapies early during recovery to prevent inactivity related problems of skin breakdown and soft tissue contractures that leads to a decreased range of motion. Assessment and fitting for splints designed to passively maintain an optimal position for limbs that cannot be actively moved is an important part of the management at this stage.The long-term management of TM requires attention to several issues. These are the residual effects of any spinal cord injury, including TM. In addition to chronic medical problems, there are the ongoing issues of ordering the appropriate equipment, reentry into school, re-socialization into the community and coping with the psychological effects of this condition by the patients and their families. During the early recovery period, family education is essential to develop a strategic plan for dealing with the challenges to independence following return to the community.Bladder function is almost always at least transiently impaired in patients with TM. Immediately after the onset of TM, there is frequently a period of transient loss or depression of neural activity below the involved spinal cord lesion, referred to as “spinal shock,” which lasts about 3 weeks. Following this period, two general problems can affect the bladder. The bladder can become overly sensitive, and empty after only a small amount of urine has collected, or relatively insensitive, causing the bladder to become over extended and overflow. An overly distended bladder increases the likelihood of urinary tract infections and, in time, may threaten the health of the kidneys. Depending on the dysfunction, treatment options include timed voiding, medicines, external catheters for males (a catheter connected to a condom), padding for women, intermittent internal self-catheterization, an indwelling catheter if needed, or electrical stimulation. Another major area of concern is effective management of bowel function. A common problem in spinal cord injury is difficulty with evacuation of stool, although fecal incontinence can also occur. The neurologic pathways for defecation are similar to those of the bladder. Many lacking voluntary control of the bowel may still be able to achieve continence by diet, strategic use of stool softeners and fiber, and the technique of rectal stimulation. Other aids include suppositories and oral medications. A high-fiber diet, adequate and timely fluid intake, and medications to regulate bowel evacuations are the basic components of success. Regular evaluations by medical specialists for adjustment of the bowel program are recommended to prevent potentially serious complications. There are some surgical options, although this is rarely necessary.Sexual dysfunction involves similar innervation and analogous syndromes as those found in bladder dysfunction. Treatment of sexual dysfunction should consider baseline function before the onset of TM. Of the utmost importance is adequate education and counseling about the known physical and neurologic changes that TM has on sexual functioning. Because of the similarities in innervation between sexual and bladder function, patients with sexual dysfunction should be encouraged to empty their bladders before sexual stimulation to prevent inopportune incontinence. The mainstays of treatment of erectile dysfunction in men are inhibitors of cGMP phosphodiesterase, type 5, which will allow most of men with TM to achieve adequate erections for success in intercourse through a combination of reflex and/or psychogenic mechanisms. Although less effective in women, these same types of medications have been shown capable of enhancing a woman’s sexual functioning. The most used oral erectile dysfunction drugs are Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). Although sexual experience is impacted by spinal cord injury, sensual experience and even orgasm are still possible. Lubricants and aids to erection and ejaculation (for fertility) are available. Adjustment to altered sexuality is aided by an attitude of permissive experimentation, as the previous methods and habits may no longer serve.Skin breakdown occurs if the skin is exposed to pressure for a significant amount of time, without sensation or the strength to shift position as necessary. The sitting position should be changed at least every 15 minutes. This can be accomplished by standing, by lifting the body up while pushing down on armrests, or by just leaning and weight shifting. Wheelchairs can be supplied with either power mechanisms of recline or tilt-in-space to redistribute weight bearing. A variety of wheelchair cushions are available to minimize sitting pressure. Redness that does not blanch when finger pressure is applied may signal the beginning of a pressure ulcer. Good nutrition, vitamin C, and avoidance of moisture all contribute to healthy skin. Pressure ulcers are much easier to prevent than to heal.Spasticity is often a very difficult problem to manage. The goal is to maintain flexibility with a stretching routine using exercises for active stretching and a bracing program with splints for a prolonged stretch. These splints are commonly used at the ankles, wrists, or elbows. Also recommended are appropriate strengthening programs for the weaker of the spastic muscles acting on a joint and an aerobic conditioning regimen. These interventions are supported by adjunctive measures that include muscle relaxant drugs (e.g., diazepam, baclofen, dantrolene, tizanidine), therapeutic botulinum toxin injections and serial casting. The therapeutic goal is to improve the function of the individual in performing specific activities of daily living (i.e., feeding, dressing, bathing, hygiene, mobility) by improving the available joint range of motion, teaching effective compensatory strategies and relieving pain.Individuals with TM may find ordinary tasks such as dressing, bathing, grooming and eating very difficult. Many of these obstacles can be mastered with training and specialized equipment. For example, long handled sponges can make bathing easier as can grab bars, portable bath seats and hand-held shower heads. For dressing, elastic shoelaces can eliminate the need to tie shoes while other devices can aid in donning socks. Occupational therapists are specialists in assessing equipment needs and helping people with limited function perform activities of daily living. A home assessment by an experienced professional is often helpful.Physical therapists assist with mobility. Besides teaching people to walk and transfer more easily, they can recommend mobility aids. This includes everything from canes (single point vs. small quad cane vs. large quad cane) to walkers (static vs. rolling vs. rollator) and braces. For a custom-fabricated orthotic (brace), an orthotist is necessary. Careful thought should go into deciding whether the brace should be an ankle-foot orthosis, whether it should be flexible or stiff, and what angle the foot portion should be in relationship to the calf portion. Some will benefit by a knee-ankle foot orthosis. Each person should be evaluated individually. The best results occur when a physician coordinates the team so that the therapists and orthotists are united on what is to be achieved. The physician best trained to take this role is the physiatrist.Pain is common following transverse myelitis. The first step in treating pain effectively is obtaining an accurate diagnosis. Unfortunately, this can be very difficult. Causes of pain include muscle strain from using the body in an unaccustomed manner, nerve compression (i.e., compression of the ulnar nerve at the elbow due to excessive pressure from resting the elbow on an armrest continuously) or dysfunction of the spinal cord from the damage caused by the inflammatory attack. Muscle pain might be treated with analgesics, such as acetaminophen (Tylenol), non-steroidal, anti-inflammatory drugs such as naproxen or ibuprofen (Naprosyn, Alleve, Motrin) or modalities such as heat or cold. Nerve compression might be treated with repositioning and padding (i.e., an elbow pad for an ulnar nerve compression).Nerve pain can be a significant challenge to find effective treatment. Nerve messages traveling through the damaged portion of the spinal cord may become scrambled and misinterpreted by the brain as pain. Besides the treatments listed above, certain antidepressants such as amitriptyline (Elavil) or anticonvulsants, such as carbamazepine, phenytoin, pregabalin, gabapentin or lamotrigine (Tegretol, Dilantin, Lyrica, Neurontin, Lamictal) may be helpful. Stress and depression should also be addressed since these conditions make pain harder to tolerate.Individuals with TM should be educated about the effect of TM on mood regulation and routinely screened for the development of symptoms consistent with clinical depression. Warning signs that should prompt a complete evaluation for depression include failure to progress with rehabilitation and self-care, worsening fixed low mood, pervasive decreased interest and/or social and professional withdrawal. A preoccupation with death or suicidal thoughts constitutes a true psychiatric emergency and should lead to prompt evaluation and treatment. Depression in TM is similar to the other neurologic symptoms patients endure, which are mediated by the effects of the immune system on the brain. Depression is remarkably prevalent in TM, occurring in up to 25% of those diagnosed at any given time, and is thought to be largely independent of the patient’s degree of physical disability. Depression is not due to personal weakness or the inability to “cope.” It can have devastating consequences; not only can depression worsen physical disability (such as fatigue, pain, and decreased concentration) but it can have lethal consequences. Suicide is the leading cause of death in TM. Despite the severity of the clinical presentation of depression in TM, there is a very robust response to combined aggressive psychopharmacologic and psychotherapeutic interventions. With appropriate recognition and treatment of TM depression, complete symptom remission is standard.
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Therapies of Transverse Myelitis. Intravenous Steroids
Intravenous steroid treatment is the first line of therapy often used in acute TM. Corticosteroids have multiple mechanisms of action including anti-inflammatory activity, immunosuppressive properties and antiproliferative actions. Though there is no randomized double-blind placebo-controlled study that supports this approach, evidence from related disorders and clinical experience support this treatment. At the Johns Hopkins TM Center, the standard of care includes intravenous methylprednisolone (1000 mg) or dexamethasone (200 mg) for 3 to 5 days unless there are compelling reasons to avoid this therapy. However, high dose steroid treatment intravenously may be given for 3-7 days. The decision to offer continued steroids or to add a new treatment is often based on the clinical course, the underlying cause and MRI appearance at the end of high dose steroid course. Plasma Exchange (PLEX)
PLEX is often initiated in moderate to severe TM (i.e., inability to walk, markedly impaired autonomic function, and sensory loss in the lower extremities) in individuals who show little clinical improvement after instituting 5 to 7 days of intravenous steroids but may also be initiated at first presentation. PLEX is believed to work in autoimmune CNS diseases through the removal of specific or nonspecific soluble factors likely to mediate, be responsible for, or contribute to inflammatory-mediated target organ damage. PLEX has been shown to be effective in adults with TM and other acute inflammatory disorders of the CNS.Other Immunomodulatory Treatment
If there is continued progression despite intravenous steroid therapy and PLEX, pulse dose intravenous cyclophosphamide (750-1000 mg/m2) is considered. Cyclophosphamide is known to have immunosuppressive properties. From the Johns Hopkins TM Center experience, it has been reported that PLEX provided an added benefit to steroids in patients who were not at a disability level of ASIA A at nadir and who did not have a history of autoimmune disease. For those who were classified at a disability level of ASIA A at their nadir, they showed a significant benefit when given combination therapy with steroids, PLEX and IV cyclophosphamide. Cyclophosphamide should be administered under the supervision of an experienced oncology team, and caregivers should monitor the patient carefully for hemorrhagic cystitis and cytopenia.Chronic immunomodulatory therapy should be considered for recurrent TM. The ideal treatment regimen is not known, and it is important for your neurologist to consult with a specialist who has significant experience in treating these rare, recurrent neuroimmunologic disorders.Long-term Care and Management
After the acute phase, rehabilitative care to improve functional skills and prevent secondary complications of immobility involves both psychological and physical accommodations. There is very little written in the medical literature specifically dealing with rehabilitation after transverse myelitis. However, much has been written regarding recovery from spinal cord injury (SCI) in general, and this literature applies. The physical issues include bowel and bladder management, sexuality, maintenance of skin integrity, spasticity, activities of daily living (i.e., dressing), mobility, and pain.It is important to begin occupational and physical therapies early during recovery to prevent inactivity related problems of skin breakdown and soft tissue contractures that leads to a decreased range of motion. Assessment and fitting for splints designed to passively maintain an optimal position for limbs that cannot be actively moved is an important part of the management at this stage.The long-term management of TM requires attention to several issues. These are the residual effects of any spinal cord injury, including TM. In addition to chronic medical problems, there are the ongoing issues of ordering the appropriate equipment, reentry into school, re-socialization into the community and coping with the psychological effects of this condition by the patients and their families. During the early recovery period, family education is essential to develop a strategic plan for dealing with the challenges to independence following return to the community.Bladder function is almost always at least transiently impaired in patients with TM. Immediately after the onset of TM, there is frequently a period of transient loss or depression of neural activity below the involved spinal cord lesion, referred to as “spinal shock,” which lasts about 3 weeks. Following this period, two general problems can affect the bladder. The bladder can become overly sensitive, and empty after only a small amount of urine has collected, or relatively insensitive, causing the bladder to become over extended and overflow. An overly distended bladder increases the likelihood of urinary tract infections and, in time, may threaten the health of the kidneys. Depending on the dysfunction, treatment options include timed voiding, medicines, external catheters for males (a catheter connected to a condom), padding for women, intermittent internal self-catheterization, an indwelling catheter if needed, or electrical stimulation. Another major area of concern is effective management of bowel function. A common problem in spinal cord injury is difficulty with evacuation of stool, although fecal incontinence can also occur. The neurologic pathways for defecation are similar to those of the bladder. Many lacking voluntary control of the bowel may still be able to achieve continence by diet, strategic use of stool softeners and fiber, and the technique of rectal stimulation. Other aids include suppositories and oral medications. A high-fiber diet, adequate and timely fluid intake, and medications to regulate bowel evacuations are the basic components of success. Regular evaluations by medical specialists for adjustment of the bowel program are recommended to prevent potentially serious complications. There are some surgical options, although this is rarely necessary.Sexual dysfunction involves similar innervation and analogous syndromes as those found in bladder dysfunction. Treatment of sexual dysfunction should consider baseline function before the onset of TM. Of the utmost importance is adequate education and counseling about the known physical and neurologic changes that TM has on sexual functioning. Because of the similarities in innervation between sexual and bladder function, patients with sexual dysfunction should be encouraged to empty their bladders before sexual stimulation to prevent inopportune incontinence. The mainstays of treatment of erectile dysfunction in men are inhibitors of cGMP phosphodiesterase, type 5, which will allow most of men with TM to achieve adequate erections for success in intercourse through a combination of reflex and/or psychogenic mechanisms. Although less effective in women, these same types of medications have been shown capable of enhancing a woman’s sexual functioning. The most used oral erectile dysfunction drugs are Viagra (sildenafil), Levitra (vardenafil) and Cialis (tadalafil). Although sexual experience is impacted by spinal cord injury, sensual experience and even orgasm are still possible. Lubricants and aids to erection and ejaculation (for fertility) are available. Adjustment to altered sexuality is aided by an attitude of permissive experimentation, as the previous methods and habits may no longer serve.Skin breakdown occurs if the skin is exposed to pressure for a significant amount of time, without sensation or the strength to shift position as necessary. The sitting position should be changed at least every 15 minutes. This can be accomplished by standing, by lifting the body up while pushing down on armrests, or by just leaning and weight shifting. Wheelchairs can be supplied with either power mechanisms of recline or tilt-in-space to redistribute weight bearing. A variety of wheelchair cushions are available to minimize sitting pressure. Redness that does not blanch when finger pressure is applied may signal the beginning of a pressure ulcer. Good nutrition, vitamin C, and avoidance of moisture all contribute to healthy skin. Pressure ulcers are much easier to prevent than to heal.Spasticity is often a very difficult problem to manage. The goal is to maintain flexibility with a stretching routine using exercises for active stretching and a bracing program with splints for a prolonged stretch. These splints are commonly used at the ankles, wrists, or elbows. Also recommended are appropriate strengthening programs for the weaker of the spastic muscles acting on a joint and an aerobic conditioning regimen. These interventions are supported by adjunctive measures that include muscle relaxant drugs (e.g., diazepam, baclofen, dantrolene, tizanidine), therapeutic botulinum toxin injections and serial casting. The therapeutic goal is to improve the function of the individual in performing specific activities of daily living (i.e., feeding, dressing, bathing, hygiene, mobility) by improving the available joint range of motion, teaching effective compensatory strategies and relieving pain.Individuals with TM may find ordinary tasks such as dressing, bathing, grooming and eating very difficult. Many of these obstacles can be mastered with training and specialized equipment. For example, long handled sponges can make bathing easier as can grab bars, portable bath seats and hand-held shower heads. For dressing, elastic shoelaces can eliminate the need to tie shoes while other devices can aid in donning socks. Occupational therapists are specialists in assessing equipment needs and helping people with limited function perform activities of daily living. A home assessment by an experienced professional is often helpful.Physical therapists assist with mobility. Besides teaching people to walk and transfer more easily, they can recommend mobility aids. This includes everything from canes (single point vs. small quad cane vs. large quad cane) to walkers (static vs. rolling vs. rollator) and braces. For a custom-fabricated orthotic (brace), an orthotist is necessary. Careful thought should go into deciding whether the brace should be an ankle-foot orthosis, whether it should be flexible or stiff, and what angle the foot portion should be in relationship to the calf portion. Some will benefit by a knee-ankle foot orthosis. Each person should be evaluated individually. The best results occur when a physician coordinates the team so that the therapists and orthotists are united on what is to be achieved. The physician best trained to take this role is the physiatrist.Pain is common following transverse myelitis. The first step in treating pain effectively is obtaining an accurate diagnosis. Unfortunately, this can be very difficult. Causes of pain include muscle strain from using the body in an unaccustomed manner, nerve compression (i.e., compression of the ulnar nerve at the elbow due to excessive pressure from resting the elbow on an armrest continuously) or dysfunction of the spinal cord from the damage caused by the inflammatory attack. Muscle pain might be treated with analgesics, such as acetaminophen (Tylenol), non-steroidal, anti-inflammatory drugs such as naproxen or ibuprofen (Naprosyn, Alleve, Motrin) or modalities such as heat or cold. Nerve compression might be treated with repositioning and padding (i.e., an elbow pad for an ulnar nerve compression).Nerve pain can be a significant challenge to find effective treatment. Nerve messages traveling through the damaged portion of the spinal cord may become scrambled and misinterpreted by the brain as pain. Besides the treatments listed above, certain antidepressants such as amitriptyline (Elavil) or anticonvulsants, such as carbamazepine, phenytoin, pregabalin, gabapentin or lamotrigine (Tegretol, Dilantin, Lyrica, Neurontin, Lamictal) may be helpful. Stress and depression should also be addressed since these conditions make pain harder to tolerate.Individuals with TM should be educated about the effect of TM on mood regulation and routinely screened for the development of symptoms consistent with clinical depression. Warning signs that should prompt a complete evaluation for depression include failure to progress with rehabilitation and self-care, worsening fixed low mood, pervasive decreased interest and/or social and professional withdrawal. A preoccupation with death or suicidal thoughts constitutes a true psychiatric emergency and should lead to prompt evaluation and treatment. Depression in TM is similar to the other neurologic symptoms patients endure, which are mediated by the effects of the immune system on the brain. Depression is remarkably prevalent in TM, occurring in up to 25% of those diagnosed at any given time, and is thought to be largely independent of the patient’s degree of physical disability. Depression is not due to personal weakness or the inability to “cope.” It can have devastating consequences; not only can depression worsen physical disability (such as fatigue, pain, and decreased concentration) but it can have lethal consequences. Suicide is the leading cause of death in TM. Despite the severity of the clinical presentation of depression in TM, there is a very robust response to combined aggressive psychopharmacologic and psychotherapeutic interventions. With appropriate recognition and treatment of TM depression, complete symptom remission is standard.
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Overview of Treacher Collins Syndrome
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SummaryTreacher Collins syndrome (TCS) is a rare genetic disorder characterized by distinctive abnormalities of the head and face. Craniofacial abnormalities tend to involve underdevelopment of the zygomatic complex, cheekbones, jaws, palate and mouth which can lead to breathing and feeding difficulties. In addition, affected individuals may also have malformations of the eyes including a downward slant of the opening between the upper and lower eyelids (palpebral fissures) and anomalies of external and middle ear structures, which may result in hearing loss. Brain and behavioral anomalies such as microcephaly and psychomotor delay have also been occasionally reported as part of the condition. The specific symptoms and physical characteristics associated with TCS can vary greatly from one individual to another. Some individuals may be so mildly affected as to go undiagnosed, while others may develop serious, life-threatening complications. TCS is primarily caused by changes (mutations) in the TCOF1 gene, but is also associated with mutations in the POLR1B, POLR1C or POLR1D genes. In the case of TCOF1 and POLR1B, the mode of inheritance is autosomal dominant, while for POLR1C it is autosomal recessive. In contrast, both autosomal dominant and recessive mutations in POLR1D have been reported in association with TCS.IntroductionTCS is named after Edward Treacher Collins, a London ophthalmologist who first described the disorder in the medical literature in 1900. TCS is also known as mandibulofacial dysostosis or Treacher Collins-Franceschetti syndrome.
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Overview of Treacher Collins Syndrome. SummaryTreacher Collins syndrome (TCS) is a rare genetic disorder characterized by distinctive abnormalities of the head and face. Craniofacial abnormalities tend to involve underdevelopment of the zygomatic complex, cheekbones, jaws, palate and mouth which can lead to breathing and feeding difficulties. In addition, affected individuals may also have malformations of the eyes including a downward slant of the opening between the upper and lower eyelids (palpebral fissures) and anomalies of external and middle ear structures, which may result in hearing loss. Brain and behavioral anomalies such as microcephaly and psychomotor delay have also been occasionally reported as part of the condition. The specific symptoms and physical characteristics associated with TCS can vary greatly from one individual to another. Some individuals may be so mildly affected as to go undiagnosed, while others may develop serious, life-threatening complications. TCS is primarily caused by changes (mutations) in the TCOF1 gene, but is also associated with mutations in the POLR1B, POLR1C or POLR1D genes. In the case of TCOF1 and POLR1B, the mode of inheritance is autosomal dominant, while for POLR1C it is autosomal recessive. In contrast, both autosomal dominant and recessive mutations in POLR1D have been reported in association with TCS.IntroductionTCS is named after Edward Treacher Collins, a London ophthalmologist who first described the disorder in the medical literature in 1900. TCS is also known as mandibulofacial dysostosis or Treacher Collins-Franceschetti syndrome.
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Symptoms of Treacher Collins Syndrome
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The symptoms and severity of TCS can vary dramatically from one person to another, even among members of the same family. Some individuals may be so mildly affected that they can go undiagnosed; others may have significant abnormalities and the potential for life-threatening respiratory complications. It is important to note that affected individuals will not have all of the symptoms discussed below.The major characteristic features of TCS encompass certain bones of the face, ears and soft tissues around the eyes. Affected individuals present with distinctive facial features and potentially develop hearing and vision problems. The abnormalities of TCS are typically symmetric (almost identical on both sides of the face) and are present at birth (congenital). Speech and language development can be compromised by hearing loss, cleft palate or jaw and airway problems. Intelligence is usually unaffected but brain and behavioral anomalies such as microcephaly and cognitive delay have been reported infrequently as part of the condition.Infants with TCS exhibit underdeveloped (hypoplastic) or absent cheekbones (malars), causing this area of the face to appear flat or sunken. The bone of the lower jaw (mandible) is incompletely developed (mandibular hypoplasia), causing the chin and the lower jaw to appear abnormally small (micrognathia). Certain bony structures (e.g., coronoid and condyloid processes) that anchor portions of the lower jaw bone to muscle can be unusually flat or absent. Affected infants may also exhibit underdevelopment of the throat (pharyngeal hypoplasia). Pharyngeal hypoplasia with underdevelopment of the lower jaw (mandibular hypoplasia) and/or abnormal smallness of the jaw (micrognathia) may contribute to feeding problems and/or breathing difficulties (respiratory insufficiency) during early infancy. Children may experience obstructive sleep apnea which is characterized by repeated short interruptions of normal breathing and air movement during sleep. In some severely-affected individuals, life-threatening respiratory difficulties may develop. (For more information on this condition, choose “Infantile Apnea” as your search term in the Rare Disease Database.)Additional abnormalities that may contribute to respiratory or feeding difficulties include narrowing or obstruction of the nasal airways (choanal stenosis or atresia). Some children may be described as having features of “Pierre Robin sequence” which include severe micrognathia, a tongue that is displaced farther back in the mouth than normal (glossoptosis) with or without incomplete closure of the roof of the mouth (cleft palate). Even in patients where the palate fuses, it may remain high arched which can still affect feeding and respiration. In addition, malformations of the mouth and the jaw may result in dental abnormalities, such as teeth that are underdeveloped (hypoplastic) and/or misaligned (malocclusion). Additional dental abnormalities have also been reported including missing teeth (tooth agenesis), clouding or discoloration of the enamel of teeth (enamel opacity), and improper (ectopic) eruption of certain upper teeth (maxillary molars).Individuals with TCS may develop hearing loss due to the failure of sound waves to be conducted through the middle ear (conductive hearing loss). Conductive hearing loss usually results from abnormalities affecting structures within the middle ear and individuals with TCS may also have malformed or absent ossicles, the three small bones through which sound waves are transmitted in the middle ear (i.e., incus, malleus, and stapes). In addition, the external ear structures are often absent, small or malformed (microtia), with narrowing (stenosis) or blockage (atresia) of the external ear canals. The outer ears may be crumpled or rotated. In contrast, the inner ear is usually unaffected, although malformation of the bony spiral organ in the inner ear (cochlea) and the structures within the inner ear that play a role in balance (vestibular apparatus) have been reported. Additional symptoms may include the presence of small growths of skin or pits just in front of the external ear (preauricular tags) and an abnormal passage that is closed on one end (blind fistula) that normally drains the ears to the nose.Many infants with TCS have abnormalities of the tissue surrounding the eyes. These eye differences can give affected individuals a saddened facial appearance. The most common ocular symptom is a downward slant to the opening between the upper and lower eyelids (palpebral fissures). Additional symptoms include a lower eyelid notch or cleft of missing lid tissue (lid coloboma), partial absence of eyelashes on the lower eyelid, crossed eyes (strabismus) and narrowed tear ducts (dacrostenosis). Occasionally malformations of the globe are seen and can include notch or cleft of missing tissue of the iris or abnormally small eyes (microphthalmia). Vision loss may occur in some patients. The degree of visual impairment varies depending upon the severity and combination of ocular abnormalities. Lower eyelid abnormalities can cause the eyes to dry out, which increases the risk of chronic irritation and eye infections.Approximately 5% of individuals with TCS display development deficits or neurological problems such as psychomotor delay. However, intelligence is generally unaffected with normal language development. Nonetheless, issues with speech development can occur because of hearing loss, cleft palate or difficulties producing sounds because of structural distortion. Some individuals with TCS exhibit additional physical abnormalities such as widely spaced eyes, notching of the upper eyelid, nasal deformity, an abnormally wide mouth (macrostomia), unusual growth of the scalp hair toward the cheeks, congenital heart defects and/or gastrointestinal malformation.
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Symptoms of Treacher Collins Syndrome. The symptoms and severity of TCS can vary dramatically from one person to another, even among members of the same family. Some individuals may be so mildly affected that they can go undiagnosed; others may have significant abnormalities and the potential for life-threatening respiratory complications. It is important to note that affected individuals will not have all of the symptoms discussed below.The major characteristic features of TCS encompass certain bones of the face, ears and soft tissues around the eyes. Affected individuals present with distinctive facial features and potentially develop hearing and vision problems. The abnormalities of TCS are typically symmetric (almost identical on both sides of the face) and are present at birth (congenital). Speech and language development can be compromised by hearing loss, cleft palate or jaw and airway problems. Intelligence is usually unaffected but brain and behavioral anomalies such as microcephaly and cognitive delay have been reported infrequently as part of the condition.Infants with TCS exhibit underdeveloped (hypoplastic) or absent cheekbones (malars), causing this area of the face to appear flat or sunken. The bone of the lower jaw (mandible) is incompletely developed (mandibular hypoplasia), causing the chin and the lower jaw to appear abnormally small (micrognathia). Certain bony structures (e.g., coronoid and condyloid processes) that anchor portions of the lower jaw bone to muscle can be unusually flat or absent. Affected infants may also exhibit underdevelopment of the throat (pharyngeal hypoplasia). Pharyngeal hypoplasia with underdevelopment of the lower jaw (mandibular hypoplasia) and/or abnormal smallness of the jaw (micrognathia) may contribute to feeding problems and/or breathing difficulties (respiratory insufficiency) during early infancy. Children may experience obstructive sleep apnea which is characterized by repeated short interruptions of normal breathing and air movement during sleep. In some severely-affected individuals, life-threatening respiratory difficulties may develop. (For more information on this condition, choose “Infantile Apnea” as your search term in the Rare Disease Database.)Additional abnormalities that may contribute to respiratory or feeding difficulties include narrowing or obstruction of the nasal airways (choanal stenosis or atresia). Some children may be described as having features of “Pierre Robin sequence” which include severe micrognathia, a tongue that is displaced farther back in the mouth than normal (glossoptosis) with or without incomplete closure of the roof of the mouth (cleft palate). Even in patients where the palate fuses, it may remain high arched which can still affect feeding and respiration. In addition, malformations of the mouth and the jaw may result in dental abnormalities, such as teeth that are underdeveloped (hypoplastic) and/or misaligned (malocclusion). Additional dental abnormalities have also been reported including missing teeth (tooth agenesis), clouding or discoloration of the enamel of teeth (enamel opacity), and improper (ectopic) eruption of certain upper teeth (maxillary molars).Individuals with TCS may develop hearing loss due to the failure of sound waves to be conducted through the middle ear (conductive hearing loss). Conductive hearing loss usually results from abnormalities affecting structures within the middle ear and individuals with TCS may also have malformed or absent ossicles, the three small bones through which sound waves are transmitted in the middle ear (i.e., incus, malleus, and stapes). In addition, the external ear structures are often absent, small or malformed (microtia), with narrowing (stenosis) or blockage (atresia) of the external ear canals. The outer ears may be crumpled or rotated. In contrast, the inner ear is usually unaffected, although malformation of the bony spiral organ in the inner ear (cochlea) and the structures within the inner ear that play a role in balance (vestibular apparatus) have been reported. Additional symptoms may include the presence of small growths of skin or pits just in front of the external ear (preauricular tags) and an abnormal passage that is closed on one end (blind fistula) that normally drains the ears to the nose.Many infants with TCS have abnormalities of the tissue surrounding the eyes. These eye differences can give affected individuals a saddened facial appearance. The most common ocular symptom is a downward slant to the opening between the upper and lower eyelids (palpebral fissures). Additional symptoms include a lower eyelid notch or cleft of missing lid tissue (lid coloboma), partial absence of eyelashes on the lower eyelid, crossed eyes (strabismus) and narrowed tear ducts (dacrostenosis). Occasionally malformations of the globe are seen and can include notch or cleft of missing tissue of the iris or abnormally small eyes (microphthalmia). Vision loss may occur in some patients. The degree of visual impairment varies depending upon the severity and combination of ocular abnormalities. Lower eyelid abnormalities can cause the eyes to dry out, which increases the risk of chronic irritation and eye infections.Approximately 5% of individuals with TCS display development deficits or neurological problems such as psychomotor delay. However, intelligence is generally unaffected with normal language development. Nonetheless, issues with speech development can occur because of hearing loss, cleft palate or difficulties producing sounds because of structural distortion. Some individuals with TCS exhibit additional physical abnormalities such as widely spaced eyes, notching of the upper eyelid, nasal deformity, an abnormally wide mouth (macrostomia), unusual growth of the scalp hair toward the cheeks, congenital heart defects and/or gastrointestinal malformation.
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Causes of Treacher Collins Syndrome
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TCS is caused by mutation of the TCOF1, POLR1B, POLR1C or POLR1D genes. In the case of TCOF1 the mode of inheritance is autosomal dominant, although very rare cases of autosomal recessive mutations have been observed. Mutations in POLR1B are autosomal dominant, whereas in POLR1C they are autosomal recessive, and for POLR1D, can be autosomal dominant or autosomal recessive. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. For TCOF1, POLR1B and POLR1D, the abnormal gene can be inherited from either parent, or can be the result of a new mutation (spontaneous gene change) in the affected individual. In approximately 60% of TCS patients, the mutation is a new mutation that occurs randomly (spontaneously) without a previous family history of the disorder (de novo mutation). However, a parent may be mildly affected and unaware that they have the disorder. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for male and female children. Irrespective of whether the mutation is inherited from the mother or father, it appears to have no bearing on severity of the TCS condition in their children.Recessive genetic disorders (e.g. TCS caused by POLR1C or POLR1D mutations) 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 unaffected for that particular trait is 25%.Mutations of the TCOF1 gene cause most (approximately 80%) cases of TCS. TCOF1 carries instructions that encode (create) a protein known as treacle. The precise role that treacle plays in the development of TCS is not fully understood. Researchers have determined that treacle plays a role in the creation of certain small structures found within cells that assemble proteins (ribosomes). This is particularly important for the formation of a group of cells called neural crest cells which form very early during embryonic development and give rise to most of the bone and cartilage underlying the face.Conditions that arise from defects in the formation (biogenesis) of ribosomes are termed ribosomopathies. POLR1B encodes a subunit of RNA polymerase 1, whereas POLR1C and POLR1D encode subunits of RNA polymerases I and III, each of which are also essential for ribosome biogenesis. It seems likely that mutations in TCOF1, POLR1B, POLR1C and POLR1D cause insufficient protein assembly and do not allow specific neural and neural crest cells to meet their proliferation and growth needs during the development of the embryo. Because TCS is highly variable, researchers speculate that additional genetic and possibly environmental factors may also play a role in the variable severity of the disorder. In support of this concept, recent experimental data has indicated that treacle plays a critical role in protection against oxidative stress induced DNA damage in neural cells, as well as in spindle orientation during neural cell division, both of which subsequently affects head and facial development.
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Causes of Treacher Collins Syndrome. TCS is caused by mutation of the TCOF1, POLR1B, POLR1C or POLR1D genes. In the case of TCOF1 the mode of inheritance is autosomal dominant, although very rare cases of autosomal recessive mutations have been observed. Mutations in POLR1B are autosomal dominant, whereas in POLR1C they are autosomal recessive, and for POLR1D, can be autosomal dominant or autosomal recessive. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. For TCOF1, POLR1B and POLR1D, the abnormal gene can be inherited from either parent, or can be the result of a new mutation (spontaneous gene change) in the affected individual. In approximately 60% of TCS patients, the mutation is a new mutation that occurs randomly (spontaneously) without a previous family history of the disorder (de novo mutation). However, a parent may be mildly affected and unaware that they have the disorder. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for male and female children. Irrespective of whether the mutation is inherited from the mother or father, it appears to have no bearing on severity of the TCS condition in their children.Recessive genetic disorders (e.g. TCS caused by POLR1C or POLR1D mutations) 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 unaffected for that particular trait is 25%.Mutations of the TCOF1 gene cause most (approximately 80%) cases of TCS. TCOF1 carries instructions that encode (create) a protein known as treacle. The precise role that treacle plays in the development of TCS is not fully understood. Researchers have determined that treacle plays a role in the creation of certain small structures found within cells that assemble proteins (ribosomes). This is particularly important for the formation of a group of cells called neural crest cells which form very early during embryonic development and give rise to most of the bone and cartilage underlying the face.Conditions that arise from defects in the formation (biogenesis) of ribosomes are termed ribosomopathies. POLR1B encodes a subunit of RNA polymerase 1, whereas POLR1C and POLR1D encode subunits of RNA polymerases I and III, each of which are also essential for ribosome biogenesis. It seems likely that mutations in TCOF1, POLR1B, POLR1C and POLR1D cause insufficient protein assembly and do not allow specific neural and neural crest cells to meet their proliferation and growth needs during the development of the embryo. Because TCS is highly variable, researchers speculate that additional genetic and possibly environmental factors may also play a role in the variable severity of the disorder. In support of this concept, recent experimental data has indicated that treacle plays a critical role in protection against oxidative stress induced DNA damage in neural cells, as well as in spindle orientation during neural cell division, both of which subsequently affects head and facial development.
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Affects of Treacher Collins Syndrome
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TCS affects males and females in equal numbers. The prevalence is estimated to be between 1 in 10,000-50,000 individuals in the general population. Some mildly affected individuals may go undiagnosed, making it difficult to determine the disorder’s true frequency in the general population. It is therefore highly recommended, that the parents and perhaps siblings of a child affected with TCS in association with a mutation in TCOF1, POLR1B, POLR1C or POLR1D, be tested even if they appear unaffected. This is important for future family planning. It should not be assumed that the mutation in an affected child occurred spontaneously, just because each parent exhibits no facial differences. However, it should be noted that some individuals (approximately 10-15%) with the features and physical findings of TCS do not have mutations in any of the four above mentioned genes, suggesting that additional as yet unidentified genes may also cause TCS.
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Affects of Treacher Collins Syndrome. TCS affects males and females in equal numbers. The prevalence is estimated to be between 1 in 10,000-50,000 individuals in the general population. Some mildly affected individuals may go undiagnosed, making it difficult to determine the disorder’s true frequency in the general population. It is therefore highly recommended, that the parents and perhaps siblings of a child affected with TCS in association with a mutation in TCOF1, POLR1B, POLR1C or POLR1D, be tested even if they appear unaffected. This is important for future family planning. It should not be assumed that the mutation in an affected child occurred spontaneously, just because each parent exhibits no facial differences. However, it should be noted that some individuals (approximately 10-15%) with the features and physical findings of TCS do not have mutations in any of the four above mentioned genes, suggesting that additional as yet unidentified genes may also cause TCS.
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Related disorders of Treacher Collins Syndrome
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Symptoms of the following disorders can be similar to those of TCS and comparisons may be useful for a differential diagnosis.Acrofacial dysostosis describes congenital syndromes, which present with craniofacial anomalies similar to those observed in mandibulofacial dysostosis conditions (ie TCS) but with the addition of limb defects. These include the well characterized disorders of Nager syndrome and Miller syndrome as well as more recently identified conditions such as acrofacial dysostosis, Cincinnati type.Nager syndrome and its more severe form Rodriguez syndrome (also known as acrofacial dysostosis – Treacher Collins type with limb anomalies) are rare inherited disorders characterized by craniofacial malformations similar to those in TCS occurring in association with abnormalities of the arms, hands, and/or feet. Craniofacial malformations include underdevelopment of the cheekbones (malar hypoplasia); incomplete development of the lower jaw (mandibular hypoplasia), causing the jaw to appear abnormally small (micrognathia); hypoplastic and/or malformed (dysplastic) external ears (pinnae) and blind ending or absent external ear canals (microtia), resulting in hearing impairment (conductive hearing loss); and/or downwardly slanted palpebral fissures, lack or absence of the lower eyelashes, and/or drooping upper eyelids (ptosis). Limb abnormalities include underdevelopment or absence of the thumbs, absence of one of the bones in the forearms (radius), abnormal fusion of bones in the forearms (radioulnar synostosis), permanent flexion of certain fingers (camptodactyly), and/or webbing of the toes (syndactyly). Nager and Rodriguez syndromes are typically inherited as an autosomal dominant trait via heterozygous mutation in the SF3B4 gene on chromosome 1q12-q21. In most cases, Nager and Rodriguez syndromes appears to occur randomly and newly in the family (sporadic) yet autosomal recessive inheritance has been previously described. (For more information on this disorder, choose “Nager” and “Rodriguez” as your search terms in the Rare Disease Database).Miller syndrome (also known as Gene-Wiedemann syndrome or postaxial acrofacial dysostosis) is a rare inherited disorder characterized by craniofacial malformations occurring in association with abnormalities of the arms, hands, and/or feet. Craniofacial malformations include underdevelopment of the cheekbones (malar hypoplasia); an abnormally small lower jaw (micrognathia); incomplete closure of the roof of the mouth (cleft palate); small, protruding, “cup-shaped” ears; and/or absence of tissue (colobomas) from the lower eyelids. Limb abnormalities may include incomplete development (hypoplasia), webbing (syndactyly), and/or absence of certain fingers and/or toes; improper positioning of certain toes; and/or improper development and/or abnormal fusion of bones in the forearms (radioulnar synostosis), causing the forearms to appear unusually short. Additional physical abnormalities can occur in some patients. Miller syndrome is inherited as an autosomal recessive trait caused by compound heterozygous mutations in the DHODH gene on chromosome 16q22.2. (For more information on this disorder, choose “Miller” as your search term in the Rare Disease Database.)Acrofacial dysostosis, Cincinnati type is a rare inherited disorder characterized by underdeveloped zygomatic arches (malar hypoplasia), maxilla and mandible (micrognathia), together with or without limb skeletal defects that include pelvic and digit anomalies. Similar to Treacher Collins syndrome, affected individuals have variable phenotypes, and additional characteristic features include downward slanting eye slits (palpebral fissures), eyelid clefts (coloboma), malformed (choanal atresia) or absent nose (anotia) and conductive hearing loss. Limb and pelvic anomalies include short and broad digits, short bowed femurs, delayed or absent bone formation (ossification). To date, all affected individuals were found to carry a heterozygous mutation in POLR1A on chromosome 2q11.2, which encodes the largest subunit of RNA Polymerase 1. POLR1A is also the catalytic subunit of RNA Polymerase 1, which transcribes ribosomal DNA genes (rDNA) into ribosomal RNA (rRNA) precursors. This process is one of the rate-limiting steps of ribosome biogenesis. Hemifacial microsomia is a rare disorder characterized by craniofacial abnormalities involving the jaws, mouth, and ears in addition to extra cranial anomalies of the cardiac, skeletal, renal systems, and extremities (HFM with expanded spectrum). Many researchers consider Goldenhar syndrome a variant and subgroup of hemifacial microsomia. In the medical literature, hemifacial microsomia and Goldenhar syndrome are often grouped together under the term “Oculoauriculovertebral (OAV) Spectrum” or “craniofacial microsomia”. Most cases occur randomly, with no apparent cause (sporadic). In other cases, there has been a positive family history that, according to some researchers, appears to suggest autosomal dominant inheritance. The physical features associated with craniofacial microsomia vary dramatically from person to person. Such features tend to involve one side of the body (unilateral) and may represent varying combinations of certain abnormalities. These include underdevelopment of the cheekbones, the upper jaw, and the lower jaw (malar, maxillary, and mandibular hypoplasia); underdevelopment of certain muscles in the face; abnormalities of the tongue, incomplete closure of the roof of the mouth (cleft palate), and/or an abnormal groove in the lip (cleft lip); malformed external ears (pinnae) with blind ending or absent external ear canals (microtia), resulting in hearing impairment (conductive hearing loss); abnormal outgrowths of skin on the ears (skin tags); and/or incomplete development of certain bones in the spinal column (vertebral hypoplasia). Additional abnormalities include partial or total absence of tissue (coloboma) from the upper eyelids, crossed eyes (strabismus), and/or abnormally small eyes (microphthalmia); heart (cardiac) defects; kidney (renal) abnormalities; and/or additional physical abnormalities. The two key features differentiating TCS from OAV Spectrum are: 1) TCS is symmetrical; and 2) TCS does not affect the nerves. (For more information on this disorder, choose “OAV Spectrum” as your search term in the Rare Disease Database.)
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Related disorders of Treacher Collins Syndrome. Symptoms of the following disorders can be similar to those of TCS and comparisons may be useful for a differential diagnosis.Acrofacial dysostosis describes congenital syndromes, which present with craniofacial anomalies similar to those observed in mandibulofacial dysostosis conditions (ie TCS) but with the addition of limb defects. These include the well characterized disorders of Nager syndrome and Miller syndrome as well as more recently identified conditions such as acrofacial dysostosis, Cincinnati type.Nager syndrome and its more severe form Rodriguez syndrome (also known as acrofacial dysostosis – Treacher Collins type with limb anomalies) are rare inherited disorders characterized by craniofacial malformations similar to those in TCS occurring in association with abnormalities of the arms, hands, and/or feet. Craniofacial malformations include underdevelopment of the cheekbones (malar hypoplasia); incomplete development of the lower jaw (mandibular hypoplasia), causing the jaw to appear abnormally small (micrognathia); hypoplastic and/or malformed (dysplastic) external ears (pinnae) and blind ending or absent external ear canals (microtia), resulting in hearing impairment (conductive hearing loss); and/or downwardly slanted palpebral fissures, lack or absence of the lower eyelashes, and/or drooping upper eyelids (ptosis). Limb abnormalities include underdevelopment or absence of the thumbs, absence of one of the bones in the forearms (radius), abnormal fusion of bones in the forearms (radioulnar synostosis), permanent flexion of certain fingers (camptodactyly), and/or webbing of the toes (syndactyly). Nager and Rodriguez syndromes are typically inherited as an autosomal dominant trait via heterozygous mutation in the SF3B4 gene on chromosome 1q12-q21. In most cases, Nager and Rodriguez syndromes appears to occur randomly and newly in the family (sporadic) yet autosomal recessive inheritance has been previously described. (For more information on this disorder, choose “Nager” and “Rodriguez” as your search terms in the Rare Disease Database).Miller syndrome (also known as Gene-Wiedemann syndrome or postaxial acrofacial dysostosis) is a rare inherited disorder characterized by craniofacial malformations occurring in association with abnormalities of the arms, hands, and/or feet. Craniofacial malformations include underdevelopment of the cheekbones (malar hypoplasia); an abnormally small lower jaw (micrognathia); incomplete closure of the roof of the mouth (cleft palate); small, protruding, “cup-shaped” ears; and/or absence of tissue (colobomas) from the lower eyelids. Limb abnormalities may include incomplete development (hypoplasia), webbing (syndactyly), and/or absence of certain fingers and/or toes; improper positioning of certain toes; and/or improper development and/or abnormal fusion of bones in the forearms (radioulnar synostosis), causing the forearms to appear unusually short. Additional physical abnormalities can occur in some patients. Miller syndrome is inherited as an autosomal recessive trait caused by compound heterozygous mutations in the DHODH gene on chromosome 16q22.2. (For more information on this disorder, choose “Miller” as your search term in the Rare Disease Database.)Acrofacial dysostosis, Cincinnati type is a rare inherited disorder characterized by underdeveloped zygomatic arches (malar hypoplasia), maxilla and mandible (micrognathia), together with or without limb skeletal defects that include pelvic and digit anomalies. Similar to Treacher Collins syndrome, affected individuals have variable phenotypes, and additional characteristic features include downward slanting eye slits (palpebral fissures), eyelid clefts (coloboma), malformed (choanal atresia) or absent nose (anotia) and conductive hearing loss. Limb and pelvic anomalies include short and broad digits, short bowed femurs, delayed or absent bone formation (ossification). To date, all affected individuals were found to carry a heterozygous mutation in POLR1A on chromosome 2q11.2, which encodes the largest subunit of RNA Polymerase 1. POLR1A is also the catalytic subunit of RNA Polymerase 1, which transcribes ribosomal DNA genes (rDNA) into ribosomal RNA (rRNA) precursors. This process is one of the rate-limiting steps of ribosome biogenesis. Hemifacial microsomia is a rare disorder characterized by craniofacial abnormalities involving the jaws, mouth, and ears in addition to extra cranial anomalies of the cardiac, skeletal, renal systems, and extremities (HFM with expanded spectrum). Many researchers consider Goldenhar syndrome a variant and subgroup of hemifacial microsomia. In the medical literature, hemifacial microsomia and Goldenhar syndrome are often grouped together under the term “Oculoauriculovertebral (OAV) Spectrum” or “craniofacial microsomia”. Most cases occur randomly, with no apparent cause (sporadic). In other cases, there has been a positive family history that, according to some researchers, appears to suggest autosomal dominant inheritance. The physical features associated with craniofacial microsomia vary dramatically from person to person. Such features tend to involve one side of the body (unilateral) and may represent varying combinations of certain abnormalities. These include underdevelopment of the cheekbones, the upper jaw, and the lower jaw (malar, maxillary, and mandibular hypoplasia); underdevelopment of certain muscles in the face; abnormalities of the tongue, incomplete closure of the roof of the mouth (cleft palate), and/or an abnormal groove in the lip (cleft lip); malformed external ears (pinnae) with blind ending or absent external ear canals (microtia), resulting in hearing impairment (conductive hearing loss); abnormal outgrowths of skin on the ears (skin tags); and/or incomplete development of certain bones in the spinal column (vertebral hypoplasia). Additional abnormalities include partial or total absence of tissue (coloboma) from the upper eyelids, crossed eyes (strabismus), and/or abnormally small eyes (microphthalmia); heart (cardiac) defects; kidney (renal) abnormalities; and/or additional physical abnormalities. The two key features differentiating TCS from OAV Spectrum are: 1) TCS is symmetrical; and 2) TCS does not affect the nerves. (For more information on this disorder, choose “OAV Spectrum” as your search term in the Rare Disease Database.)
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Diagnosis of Treacher Collins Syndrome
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A diagnosis of TCS is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic physical findings. Many associated abnormalities such as malformation or absence of the external ear are present at birth (congenital).Clinical Testing and Work-Up
Specialized X-ray studies will confirm the presence and/or extent of certain observed craniofacial abnormalities. For example, such imaging tests show the abnormal smallness of the jaw (micrognathia) due to underdevelopment of the lower jaw bone (mandibular hypoplasia), the presence and/or extent of hypoplasia affecting certain parts of the skull, and/or the presence of additional malformations of the ear that cannot be seen during clinical evaluation. In addition, in those affected individuals who exhibit few signs, a thorough clinical examination and X-ray imaging of the craniofacial area can demonstrate the subtle presence of certain characteristic features (e.g., hypoplasia of zygomatic arches) associated with TCS. Because TCS shares several physical features that may occur in other craniofacial syndromes, many researchers recommend that diagnostic confirmation be made through molecular genetic testing and/or, in some cases, a careful, detailed family history.Molecular genetic testing to confirm a diagnosis is available through commercial and academic research laboratories to detect mutations in the TCOF1, POLR1B, POLR1C and POLR1D genes. Approximately 80% of individuals have an identifiable mutation of the TCOF1 gene. Furthermore, genetic confirmation of a TCOF1, POLR1B, POLR1C, or POLR1D mutation can be detected before birth (prenatally) by amniocentesis and chorionic villus sampling if a mutation has been identified in an affected family member. In certain cases, fetal ultrasonography, which uses reflected sound waves to create an image of the developing fetus, can reveal characteristic findings suggestive of TCS. Relatives, especially parents and siblings, of an individual diagnosed with TCS should be carefully examined because mild cases often go unrecognized and undiagnosed.
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Diagnosis of Treacher Collins Syndrome. A diagnosis of TCS is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic physical findings. Many associated abnormalities such as malformation or absence of the external ear are present at birth (congenital).Clinical Testing and Work-Up
Specialized X-ray studies will confirm the presence and/or extent of certain observed craniofacial abnormalities. For example, such imaging tests show the abnormal smallness of the jaw (micrognathia) due to underdevelopment of the lower jaw bone (mandibular hypoplasia), the presence and/or extent of hypoplasia affecting certain parts of the skull, and/or the presence of additional malformations of the ear that cannot be seen during clinical evaluation. In addition, in those affected individuals who exhibit few signs, a thorough clinical examination and X-ray imaging of the craniofacial area can demonstrate the subtle presence of certain characteristic features (e.g., hypoplasia of zygomatic arches) associated with TCS. Because TCS shares several physical features that may occur in other craniofacial syndromes, many researchers recommend that diagnostic confirmation be made through molecular genetic testing and/or, in some cases, a careful, detailed family history.Molecular genetic testing to confirm a diagnosis is available through commercial and academic research laboratories to detect mutations in the TCOF1, POLR1B, POLR1C and POLR1D genes. Approximately 80% of individuals have an identifiable mutation of the TCOF1 gene. Furthermore, genetic confirmation of a TCOF1, POLR1B, POLR1C, or POLR1D mutation can be detected before birth (prenatally) by amniocentesis and chorionic villus sampling if a mutation has been identified in an affected family member. In certain cases, fetal ultrasonography, which uses reflected sound waves to create an image of the developing fetus, can reveal characteristic findings suggestive of TCS. Relatives, especially parents and siblings, of an individual diagnosed with TCS should be carefully examined because mild cases often go unrecognized and undiagnosed.
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Therapies of Treacher Collins Syndrome
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Treatment
There is no cure for TCS. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, pediatric ear, nose and throat specialists (pediatric otolaryngologists), pediatric dentist, pediatric nurse, plastic surgeon, speech pathologists, audiologists, ophthalmologists, psychologists, geneticists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Physicians regularly monitor individuals with TCS to detect certain abnormalities that may be associated with the disorder. For example, an affected individual’s hearing should be carefully monitored to detect any onset of hearing loss. Assessment of an infant’s hearing is critical and a full assessment should be done early during life, even before one year of age and then yearly, to ensure proper speech development.An instrument (ophthalmoscope) is used to visualize the interior of the eye to detect any possibility of visual impairment. This examination is important to ensure appropriate preventive steps and/or prompt treatment for those who exhibit abnormalities of the eyes in association with TCS (e.g., colobomas, strabismus, microphthalmia). Affected individuals should also be monitored for jaw and dental abnormalities.Early intervention is important to ensure that affected children reach their potential. Special services that may be beneficial include speech therapy, special social support, and other medical, social, and/or vocational services. Genetic counseling is recommended for affected individuals and their families.Surgery
In some patients, surgical reconstruction of craniofacial malformations may be necessary. Surgery may be performed to repair cleft palate, to reconstruct the jaw, or to repair other bones in the skull (e.g., malar bones, zygomatic complex). The specific surgical procedures used and the age when surgery is performed depends upon the severity of the malformations, overall health and personal preference.For example, different abnormalities may be treated at different ages. Cleft palate is often corrected around 1-2 years of age. Zygomatic and orbital reconstruction usually occurs around 5-7 years of age. External and inner ear reconstruction usually occurs around 6 years of age. Jawbone lengthening or reconstruction can range from newborn to teenager years depending upon the extent and severity of the condition.Obstructive airways can be a serious problem not always obvious to parents or clinicians. A sleep or nap study may be used to help determine the severity of the obstruction and may influence the treatment plan. In severe affected individuals, a tube may be surgically inserted into the windpipe (trachea) to maintain an effective airway, a procedure called a tracheostomy. A procedure known as mandibular distraction, which is used to increase the length of the jawbone, may be necessary. A tube may be surgically implanted into the stomach to assure that affected infants experiencing feeding difficulties receive sufficient calories (gastrostomy).Multiple surgeries may be required to treat the various craniofacial abnormalities that are associated with TCS. Despite the number of surgeries, results vary from one person to another and the end result is rarely fully corrective.In some individuals, an operation may be performed to help correct middle ear malformations and associated conductive hearing loss. However, specialized hearing aids such as bone-anchored hearing aids (BAHA) may suffice rather than surgery in most patients. Bone-anchored hearing aids transmit sound directly through bone into the inner ear, bypassing the external ear canal and the middle ear (both of which are often affected in individuals with TCS. Reconstructive surgery may be performed to help correct outer ear malformations for functional and cosmetic reasons. Generally, reconstruction of the external ear should be performed first.Additional Therapies
In individuals with TCS who exhibit eye abnormalities and associated visual impairment, corrective glasses, contact lenses, surgery, and/or other supportive techniques may be used to help improve vision in some cases. Artificial teeth (dentures), dental implants, braces, dental surgery, and/or other corrective procedures may be used to correct dental abnormalities.Anesthesia Considerations
Structural airway problems associated with TCS can make it difficult for anesthesiologists to manage and maintain an airway during surgery. Proper evaluation including a comprehensive preoperative assessment and complete clinical history should be performed to best plan an anesthetic strategy.
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Therapies of Treacher Collins Syndrome. Treatment
There is no cure for TCS. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, pediatric ear, nose and throat specialists (pediatric otolaryngologists), pediatric dentist, pediatric nurse, plastic surgeon, speech pathologists, audiologists, ophthalmologists, psychologists, geneticists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Physicians regularly monitor individuals with TCS to detect certain abnormalities that may be associated with the disorder. For example, an affected individual’s hearing should be carefully monitored to detect any onset of hearing loss. Assessment of an infant’s hearing is critical and a full assessment should be done early during life, even before one year of age and then yearly, to ensure proper speech development.An instrument (ophthalmoscope) is used to visualize the interior of the eye to detect any possibility of visual impairment. This examination is important to ensure appropriate preventive steps and/or prompt treatment for those who exhibit abnormalities of the eyes in association with TCS (e.g., colobomas, strabismus, microphthalmia). Affected individuals should also be monitored for jaw and dental abnormalities.Early intervention is important to ensure that affected children reach their potential. Special services that may be beneficial include speech therapy, special social support, and other medical, social, and/or vocational services. Genetic counseling is recommended for affected individuals and their families.Surgery
In some patients, surgical reconstruction of craniofacial malformations may be necessary. Surgery may be performed to repair cleft palate, to reconstruct the jaw, or to repair other bones in the skull (e.g., malar bones, zygomatic complex). The specific surgical procedures used and the age when surgery is performed depends upon the severity of the malformations, overall health and personal preference.For example, different abnormalities may be treated at different ages. Cleft palate is often corrected around 1-2 years of age. Zygomatic and orbital reconstruction usually occurs around 5-7 years of age. External and inner ear reconstruction usually occurs around 6 years of age. Jawbone lengthening or reconstruction can range from newborn to teenager years depending upon the extent and severity of the condition.Obstructive airways can be a serious problem not always obvious to parents or clinicians. A sleep or nap study may be used to help determine the severity of the obstruction and may influence the treatment plan. In severe affected individuals, a tube may be surgically inserted into the windpipe (trachea) to maintain an effective airway, a procedure called a tracheostomy. A procedure known as mandibular distraction, which is used to increase the length of the jawbone, may be necessary. A tube may be surgically implanted into the stomach to assure that affected infants experiencing feeding difficulties receive sufficient calories (gastrostomy).Multiple surgeries may be required to treat the various craniofacial abnormalities that are associated with TCS. Despite the number of surgeries, results vary from one person to another and the end result is rarely fully corrective.In some individuals, an operation may be performed to help correct middle ear malformations and associated conductive hearing loss. However, specialized hearing aids such as bone-anchored hearing aids (BAHA) may suffice rather than surgery in most patients. Bone-anchored hearing aids transmit sound directly through bone into the inner ear, bypassing the external ear canal and the middle ear (both of which are often affected in individuals with TCS. Reconstructive surgery may be performed to help correct outer ear malformations for functional and cosmetic reasons. Generally, reconstruction of the external ear should be performed first.Additional Therapies
In individuals with TCS who exhibit eye abnormalities and associated visual impairment, corrective glasses, contact lenses, surgery, and/or other supportive techniques may be used to help improve vision in some cases. Artificial teeth (dentures), dental implants, braces, dental surgery, and/or other corrective procedures may be used to correct dental abnormalities.Anesthesia Considerations
Structural airway problems associated with TCS can make it difficult for anesthesiologists to manage and maintain an airway during surgery. Proper evaluation including a comprehensive preoperative assessment and complete clinical history should be performed to best plan an anesthetic strategy.
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Overview of Tricho Dento Osseous Syndrome
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SummaryTricho-dento-osseous (TDO) syndrome is an autosomal dominant genetic disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. TDO syndrome may be apparent at birth due to kinky curly hair that is present in all affected newborns with hair. TDO syndrome is characterized by kinky or curly hair; poorly developed tooth enamel; and unusual thickness and/or denseness (sclerosis) of the top portion of the skull (calvaria), long bones (i.e., bones in the arms and legs), jaw and spine. These skeletal abnormalities can be seen in children as young as three years of age but are more noticeable with increasing age. Some affected children also exhibit abnormally thin, brittle nails. Most affected children have a relatively normal head shape, but some may have some variation in head shape. The treatment of TDO syndrome is directed toward the specific symptoms that are apparent in each individual.
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Overview of Tricho Dento Osseous Syndrome. SummaryTricho-dento-osseous (TDO) syndrome is an autosomal dominant genetic disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. TDO syndrome may be apparent at birth due to kinky curly hair that is present in all affected newborns with hair. TDO syndrome is characterized by kinky or curly hair; poorly developed tooth enamel; and unusual thickness and/or denseness (sclerosis) of the top portion of the skull (calvaria), long bones (i.e., bones in the arms and legs), jaw and spine. These skeletal abnormalities can be seen in children as young as three years of age but are more noticeable with increasing age. Some affected children also exhibit abnormally thin, brittle nails. Most affected children have a relatively normal head shape, but some may have some variation in head shape. The treatment of TDO syndrome is directed toward the specific symptoms that are apparent in each individual.
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Symptoms of Tricho Dento Osseous Syndrome
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TDO syndrome is characterized by abnormalities of the hair, teeth, bones, and/or nails. In addition, infants and children with TDO syndrome have tight, kinky or curly hair that may also be unusually dry. As affected individuals enter their 20s or 30s, the hair may straighten or become unusually thin. Some individuals with the disorder also have unusually long eyelashes and eyebrows. All individuals with TDO syndrome have dental abnormalities that affect both the primary (deciduous) and secondary (permanent) teeth but the range of severity is extremely variable. The tooth enamel is underdeveloped (enamel hypoplasia), with diminished mineral accumulation (hypomineralization). As a result, the tooth enamel may be abnormally thin, soft, and pitted and often discolored (i.e., yellowish-brown). Hypersensitivity of the teeth is commonly reported. Both the primary and secondary molars may be abnormally shaped (i.e., “prism” shaped), and the chambers within the teeth that contain pulp may be abnormally large (taurodontism). In addition, many teeth may also have unusually short, open roots. As a result, the teeth may be highly prone to decay (dental caries) and infection (abscess) that may cause swelling and pain. Some affected individuals also exhibit widely spaced teeth; decreased tooth width (microdontia); premature (precocious) or delayed tooth eruption; and secondary teeth that become impacted in the gums. Affected individuals may lose their teeth early, typically in the second or third decade of life. Some individuals with TDO syndrome also exhibit abnormalities of the nails. Fingernails and/or toenails may be unusually thin and brittle. In addition, the upper (superficial) layers of the nail may be prone to splitting. Other reported abnormalities include impacted teeth and curvature of fingers (clinodactyly).
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Symptoms of Tricho Dento Osseous Syndrome. TDO syndrome is characterized by abnormalities of the hair, teeth, bones, and/or nails. In addition, infants and children with TDO syndrome have tight, kinky or curly hair that may also be unusually dry. As affected individuals enter their 20s or 30s, the hair may straighten or become unusually thin. Some individuals with the disorder also have unusually long eyelashes and eyebrows. All individuals with TDO syndrome have dental abnormalities that affect both the primary (deciduous) and secondary (permanent) teeth but the range of severity is extremely variable. The tooth enamel is underdeveloped (enamel hypoplasia), with diminished mineral accumulation (hypomineralization). As a result, the tooth enamel may be abnormally thin, soft, and pitted and often discolored (i.e., yellowish-brown). Hypersensitivity of the teeth is commonly reported. Both the primary and secondary molars may be abnormally shaped (i.e., “prism” shaped), and the chambers within the teeth that contain pulp may be abnormally large (taurodontism). In addition, many teeth may also have unusually short, open roots. As a result, the teeth may be highly prone to decay (dental caries) and infection (abscess) that may cause swelling and pain. Some affected individuals also exhibit widely spaced teeth; decreased tooth width (microdontia); premature (precocious) or delayed tooth eruption; and secondary teeth that become impacted in the gums. Affected individuals may lose their teeth early, typically in the second or third decade of life. Some individuals with TDO syndrome also exhibit abnormalities of the nails. Fingernails and/or toenails may be unusually thin and brittle. In addition, the upper (superficial) layers of the nail may be prone to splitting. Other reported abnormalities include impacted teeth and curvature of fingers (clinodactyly).
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Causes of Tricho Dento Osseous Syndrome
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TDO syndrome is an autosomal dominant genetic disorder caused by a change (mutation) in the DLX3 gene. Several different mutations in the DLX3 gene have been reported. This gene is a member of the distal-less homeobox gene family. The disorder occurs because of a deletion in this gene that leads to a DLX3 protein product that is shorter than normal and does not function normally. Research has shown that the DLX3 gene plays a role in the patterning of the part of the embryo that leads to the formation of skin, teeth and ectoderm, as well as the formation of bones. This explains the presentation of the symptoms associated with TDO syndrome. 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. The risk is the same for male and female children.
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Causes of Tricho Dento Osseous Syndrome. TDO syndrome is an autosomal dominant genetic disorder caused by a change (mutation) in the DLX3 gene. Several different mutations in the DLX3 gene have been reported. This gene is a member of the distal-less homeobox gene family. The disorder occurs because of a deletion in this gene that leads to a DLX3 protein product that is shorter than normal and does not function normally. Research has shown that the DLX3 gene plays a role in the patterning of the part of the embryo that leads to the formation of skin, teeth and ectoderm, as well as the formation of bones. This explains the presentation of the symptoms associated with TDO syndrome. 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. The risk is the same for male and female children.
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Affects of Tricho Dento Osseous Syndrome
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TDO syndrome is a rare inherited disorder that affects males and females in equal numbers. Approximately 12 affected families (kindreds) have been reported in the medical literature.
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Affects of Tricho Dento Osseous Syndrome. TDO syndrome is a rare inherited disorder that affects males and females in equal numbers. Approximately 12 affected families (kindreds) have been reported in the medical literature.
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Related disorders of Tricho Dento Osseous Syndrome
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Symptoms of the following disorders can be similar to those of tricho-dento-osseous syndrome. Comparisons may be useful for a differential diagnosis: Amelogenesis imperfecta is a group of inherited conditions in which the tooth enamel is underdeveloped (hypoplastic) or there is a decreased mineral content in the enamel (hypomineralization). Almost 20 different genes are involved in these conditions. Many different forms of the disorder have been classified, based upon varying types of enamel defects. Affected individuals may have abnormally thin, soft, pitted, and/or discolored tooth enamel; heightened susceptibility to disease of the structures surrounding and supporting the teeth (periodontal disease); increased sensitivity of the teeth to hot and cold temperatures; and/or early tooth loss. (For more information on this disorder, choose “amelogenesis imperfecta” as your search term in the Rare Disease Database.) Rieger syndrome is a rare genetic disorder characterized by absent or under-developed teeth (hypodontia or oligodontia), mild craniofacial abnormalities, and various abnormalities of the eye, especially glaucoma. If unaccompanied by other signs and symptoms, the eye abnormalities are referred to as Rieger eye anomalies. (For more information on this disorder, choose “Rieger syndrome” as your search term in the Rare Disease Database). There are other congenital disorders characterized by malformations of the hair, teeth, bones, and/or nails similar to those potentially associated with TDO syndrome. These disorders include oculo-dento-osseous dysplasia and the autosomal dominant form of osteopetrosis. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Related disorders of Tricho Dento Osseous Syndrome. Symptoms of the following disorders can be similar to those of tricho-dento-osseous syndrome. Comparisons may be useful for a differential diagnosis: Amelogenesis imperfecta is a group of inherited conditions in which the tooth enamel is underdeveloped (hypoplastic) or there is a decreased mineral content in the enamel (hypomineralization). Almost 20 different genes are involved in these conditions. Many different forms of the disorder have been classified, based upon varying types of enamel defects. Affected individuals may have abnormally thin, soft, pitted, and/or discolored tooth enamel; heightened susceptibility to disease of the structures surrounding and supporting the teeth (periodontal disease); increased sensitivity of the teeth to hot and cold temperatures; and/or early tooth loss. (For more information on this disorder, choose “amelogenesis imperfecta” as your search term in the Rare Disease Database.) Rieger syndrome is a rare genetic disorder characterized by absent or under-developed teeth (hypodontia or oligodontia), mild craniofacial abnormalities, and various abnormalities of the eye, especially glaucoma. If unaccompanied by other signs and symptoms, the eye abnormalities are referred to as Rieger eye anomalies. (For more information on this disorder, choose “Rieger syndrome” as your search term in the Rare Disease Database). There are other congenital disorders characterized by malformations of the hair, teeth, bones, and/or nails similar to those potentially associated with TDO syndrome. These disorders include oculo-dento-osseous dysplasia and the autosomal dominant form of osteopetrosis. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Diagnosis of Tricho Dento Osseous Syndrome
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TDO syndrome may be suspected shortly after birth based upon a thorough clinical evaluation, characteristic physical findings (e.g., extremely kinky hair, certain craniofacial abnormalities, dysplastic nails). Genetic testing for mutations in the DLX3 gene can confirm the diagnosis. To date, researchers have identified nine different mutations in the DLX3 gene that cause TDO. The diagnosis is typically confirmed between the ages of six months to one year, when certain dental abnormalities may become apparent. Various specialized tests may contribute to diagnosis and characterization of certain associated abnormalities. For example, examination of tooth enamel under a microscope that uses an electron beam (electron microscopy) may reveal an abnormally thin enamel layer with scattered, random pits. Specialized X-ray studies may demonstrate abnormal thickening and/or density (sclerosis) of specific bones (calvaria and/or long bones) and/or other skeletal abnormalities (e.g., craniosynostosis, dolichocephaly).
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Diagnosis of Tricho Dento Osseous Syndrome. TDO syndrome may be suspected shortly after birth based upon a thorough clinical evaluation, characteristic physical findings (e.g., extremely kinky hair, certain craniofacial abnormalities, dysplastic nails). Genetic testing for mutations in the DLX3 gene can confirm the diagnosis. To date, researchers have identified nine different mutations in the DLX3 gene that cause TDO. The diagnosis is typically confirmed between the ages of six months to one year, when certain dental abnormalities may become apparent. Various specialized tests may contribute to diagnosis and characterization of certain associated abnormalities. For example, examination of tooth enamel under a microscope that uses an electron beam (electron microscopy) may reveal an abnormally thin enamel layer with scattered, random pits. Specialized X-ray studies may demonstrate abnormal thickening and/or density (sclerosis) of specific bones (calvaria and/or long bones) and/or other skeletal abnormalities (e.g., craniosynostosis, dolichocephaly).
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Therapies of Tricho Dento Osseous Syndrome
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Treatment
The treatment of TDO syndrome is focused on the specific symptoms apparent in each individual and requires the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat diseases of the bones (orthopedists), dental specialists and other health care professionals may be required to address the individual’s clinical symptoms. Specific therapies for the treatment of TDO syndrome are symptomatic and supportive. Dental abnormalities associated with the disorder may be treated with a variety of techniques. Treatment is based on keeping teeth from wearing rapidly and exposing the pulp which causes abscess formation. Teeth can be treated with bonding and crowns to preserve the dentition. Dental specialists may obtain regular X-rays and take other steps to monitor dental development in the case of premature or delayed tooth eruption, to detect impacted secondary teeth and/or to help prevent, detect, and/or treat other dental abnormalities. A variety of procedures may be used to restore improperly developed teeth to help prevent decay, abscess and/or early tooth loss. Artificial teeth and/or other devices (prosthetics) such as dental implants may be used to replace lost or absent teeth. In addition, dental surgery and/or other corrective procedures may be undertaken to correct other dental abnormalities. Early intervention may be important to ensure that children with TDO syndrome reach their potential. Special services that may be beneficial to affected children may include special social support and other medical, social, and/or vocational services. Genetic counseling is recommended for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Therapies of Tricho Dento Osseous Syndrome. Treatment
The treatment of TDO syndrome is focused on the specific symptoms apparent in each individual and requires the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat diseases of the bones (orthopedists), dental specialists and other health care professionals may be required to address the individual’s clinical symptoms. Specific therapies for the treatment of TDO syndrome are symptomatic and supportive. Dental abnormalities associated with the disorder may be treated with a variety of techniques. Treatment is based on keeping teeth from wearing rapidly and exposing the pulp which causes abscess formation. Teeth can be treated with bonding and crowns to preserve the dentition. Dental specialists may obtain regular X-rays and take other steps to monitor dental development in the case of premature or delayed tooth eruption, to detect impacted secondary teeth and/or to help prevent, detect, and/or treat other dental abnormalities. A variety of procedures may be used to restore improperly developed teeth to help prevent decay, abscess and/or early tooth loss. Artificial teeth and/or other devices (prosthetics) such as dental implants may be used to replace lost or absent teeth. In addition, dental surgery and/or other corrective procedures may be undertaken to correct other dental abnormalities. Early intervention may be important to ensure that children with TDO syndrome reach their potential. Special services that may be beneficial to affected children may include special social support and other medical, social, and/or vocational services. Genetic counseling is recommended for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
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Overview of Trichorhinophalangeal Syndrome Type I
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Trichorhinophalangeal syndrome type I (TRPS1) is an extremely rare inherited multisystem disorder. TRPS1 is characterized by thin, sparse scalp hair, unusual facial features, abnormalities of the fingers and/or toes, and multiple abnormalities of the “growing ends” (epiphyses) of the bones (skeletal dysplasia), especially in the hands and feet. Characteristic facial features may include a rounded (bulbous) “pear-shaped” nose, an abnormally small jaw (micrognathia), dental anomalies, and/or unusually large (prominent) ears. In most cases, the fingers and/or toes may be abnormally short (brachydactyly) and curved. In addition, affected individuals may exhibit short stature. The range and severity of symptoms may vary from case to case. In most cases, Trichorhinophalangeal syndrome type I has autosomal dominant inheritance.
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Overview of Trichorhinophalangeal Syndrome Type I. Trichorhinophalangeal syndrome type I (TRPS1) is an extremely rare inherited multisystem disorder. TRPS1 is characterized by thin, sparse scalp hair, unusual facial features, abnormalities of the fingers and/or toes, and multiple abnormalities of the “growing ends” (epiphyses) of the bones (skeletal dysplasia), especially in the hands and feet. Characteristic facial features may include a rounded (bulbous) “pear-shaped” nose, an abnormally small jaw (micrognathia), dental anomalies, and/or unusually large (prominent) ears. In most cases, the fingers and/or toes may be abnormally short (brachydactyly) and curved. In addition, affected individuals may exhibit short stature. The range and severity of symptoms may vary from case to case. In most cases, Trichorhinophalangeal syndrome type I has autosomal dominant inheritance.
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Symptoms of Trichorhinophalangeal Syndrome Type I
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The range and severity of symptoms of individuals with trichorhinophalangeal syndrome type I may vary from case to case. Most cases are characterized by thin, sparse scalp hair, unusual facial features, and multiple abnormalities affecting the “growing ends” (epiphyses) of certain bones, especially those in the hands and feet. The hair of affected infants may be markedly thin and sparse at birth (congenital) and is usually fine and brittle and/or may grow slowly. Affected individuals may lose most or all of their scalp hair (alopecia) at a young age, in some cases, by the second decade of life. In many cases, the eyebrows may be unusually thick near the nose and abnormally sparse by the temples. Characteristic facial features may include a rounded (bulbous), “pear-shaped” nose; a thin upper lip; an abnormally long groove (philtrum) on the upper lip, and/or a groove in the chin. Affected individuals may also have abnormally large (prominent) ears, an unusually small lower jaw (micrognathia), and/or small, discolored, and abnormally soft (carious) teeth that may be abnormally positioned (malocclusion). In some cases, extra (supernumerary) teeth may also be present. In most cases, affected individuals exhibit abnormalities of the fingers and/or toes including permanent fixation of the fifth fingers in a bent position (clinodactyly) and/or abnormal “cone-shaped” bones in the fingers (middle phalanges) and toes (epiphyseal coning). In addition, certain bones in the hands (metacarpals) and feet (metatarsals) may be abnormally short and curved. In some cases, the nails may be unusually thin and malformed (dysplastic). In rare cases, affected individuals may also have an abnormally short forearm bone (ulna) and/or flat feet (pes planus). As individuals with TRPS1 age, most exhibit delayed bone age and growth retardation, resulting in short stature. In some cases, affected individuals may develop pain and limitation of movements in the hips and/or hands; inflammation and swelling (arthritis) in the fingers, elbows, and/or spine may also develop. Some individuals with TRPS1 may develop hip problems similar to those of people with Legg-Calve-Perthes disease. These include progressive degeneration of the end portion (head) of the thigh bone (capital femoral epiphyseal osteonecrosis). (For more information on Legg-Calve-Perthes disease, see the Related Disorders section of this report.) Individuals with TRPS1 may also exhibit other physical abnormalities including abnormal prominence of the breast bone (pectus carinatum), an unusual “wing-like” shape of the shoulder blades (scapula), abnormal side-to-side curvature of the spine (scoliosis), and/or backward curvature of the spine (lordosis). In some cases, affected individuals may also experience frequent respiratory infections.
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Symptoms of Trichorhinophalangeal Syndrome Type I. The range and severity of symptoms of individuals with trichorhinophalangeal syndrome type I may vary from case to case. Most cases are characterized by thin, sparse scalp hair, unusual facial features, and multiple abnormalities affecting the “growing ends” (epiphyses) of certain bones, especially those in the hands and feet. The hair of affected infants may be markedly thin and sparse at birth (congenital) and is usually fine and brittle and/or may grow slowly. Affected individuals may lose most or all of their scalp hair (alopecia) at a young age, in some cases, by the second decade of life. In many cases, the eyebrows may be unusually thick near the nose and abnormally sparse by the temples. Characteristic facial features may include a rounded (bulbous), “pear-shaped” nose; a thin upper lip; an abnormally long groove (philtrum) on the upper lip, and/or a groove in the chin. Affected individuals may also have abnormally large (prominent) ears, an unusually small lower jaw (micrognathia), and/or small, discolored, and abnormally soft (carious) teeth that may be abnormally positioned (malocclusion). In some cases, extra (supernumerary) teeth may also be present. In most cases, affected individuals exhibit abnormalities of the fingers and/or toes including permanent fixation of the fifth fingers in a bent position (clinodactyly) and/or abnormal “cone-shaped” bones in the fingers (middle phalanges) and toes (epiphyseal coning). In addition, certain bones in the hands (metacarpals) and feet (metatarsals) may be abnormally short and curved. In some cases, the nails may be unusually thin and malformed (dysplastic). In rare cases, affected individuals may also have an abnormally short forearm bone (ulna) and/or flat feet (pes planus). As individuals with TRPS1 age, most exhibit delayed bone age and growth retardation, resulting in short stature. In some cases, affected individuals may develop pain and limitation of movements in the hips and/or hands; inflammation and swelling (arthritis) in the fingers, elbows, and/or spine may also develop. Some individuals with TRPS1 may develop hip problems similar to those of people with Legg-Calve-Perthes disease. These include progressive degeneration of the end portion (head) of the thigh bone (capital femoral epiphyseal osteonecrosis). (For more information on Legg-Calve-Perthes disease, see the Related Disorders section of this report.) Individuals with TRPS1 may also exhibit other physical abnormalities including abnormal prominence of the breast bone (pectus carinatum), an unusual “wing-like” shape of the shoulder blades (scapula), abnormal side-to-side curvature of the spine (scoliosis), and/or backward curvature of the spine (lordosis). In some cases, affected individuals may also experience frequent respiratory infections.
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Causes of Trichorhinophalangeal Syndrome Type I
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Trichorhinophalangeal syndrome type I is a rare genetic disorder with autosomal dominant inheritance. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.Researchers have located a gene involved in TRPS1. The gene, known as the TRPS1 gene, is located on the long arm (q) of the 8th chromosome (8q24.12). Some cases of TRPS1 occur due to disruption or changes (mutations) of this gene. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome. The physical findings associated with TRPS1 may vary greatly from case to case (variable expressivity). For example, some physical characteristics (e.g., abnormal rounding of the nose, short stature) may be more severe in some cases than in others.In rare cases, TRPS1 may occur as an autosomal recessive trait. Most recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. However, some individuals with TRPS1 may develop TRPS1 due to haploinsufficiency, the circumstance in which the one normal gene cannot produce enough protein to assure normal function.
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Causes of Trichorhinophalangeal Syndrome Type I. Trichorhinophalangeal syndrome type I is a rare genetic disorder with autosomal dominant inheritance. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.Researchers have located a gene involved in TRPS1. The gene, known as the TRPS1 gene, is located on the long arm (q) of the 8th chromosome (8q24.12). Some cases of TRPS1 occur due to disruption or changes (mutations) of this gene. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome. The physical findings associated with TRPS1 may vary greatly from case to case (variable expressivity). For example, some physical characteristics (e.g., abnormal rounding of the nose, short stature) may be more severe in some cases than in others.In rare cases, TRPS1 may occur as an autosomal recessive trait. Most recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. However, some individuals with TRPS1 may develop TRPS1 due to haploinsufficiency, the circumstance in which the one normal gene cannot produce enough protein to assure normal function.
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Affects of Trichorhinophalangeal Syndrome Type I
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Trichorhinophalangeal syndrome type I is an extremely rare inherited disorder that affects males and females in equal numbers. In those individuals with mild symptoms, a diagnosis may be easily missed or go unreported. Therefore, it is difficult to determine the true frequency of this disorder in the general population. Many researchers suspect there may be a higher incidence of TRPS1 than is actually reported in the medical literature.
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Affects of Trichorhinophalangeal Syndrome Type I. Trichorhinophalangeal syndrome type I is an extremely rare inherited disorder that affects males and females in equal numbers. In those individuals with mild symptoms, a diagnosis may be easily missed or go unreported. Therefore, it is difficult to determine the true frequency of this disorder in the general population. Many researchers suspect there may be a higher incidence of TRPS1 than is actually reported in the medical literature.
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Related disorders of Trichorhinophalangeal Syndrome Type I
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Symptoms of the following disorders can be similar to those of Trichorhinophalangeal Syndrome Type I. Comparisons may be useful for a differential diagnosis: Trichorhinophalangeal Syndrome Type II, also known as Langer-Giedion Syndrome, is an extremely rare inherited disorder that has many of the same symptoms and physical features associated with Trichorhinophalangeal Syndrome Type I. These may include a rounded (bulbous) nose; a long, prominent groove (philtrum) of the upper lip; thin, sparse scalp hair; abnormally short fingers and toes (brachydactyly); and/or short stature. In addition, a child with Trichorhinophalangeal Syndrome Type II may exhibit an abnormally small head (microcephaly), excess (redundant) skin, and/or multiple bony growths on various bones of the body (exostoses). In some cases, mental retardation may also be present. Most cases of Trichorhinophalangeal Syndrome Type II occur randomly (sporadically) and are due to the absence of genetic material (chromosomal deletions) on chromsome 8 at the same site in Trichorhinophalangeal Syndrome Type I. (For more information on this disorder, choose ” Trichorhinophalangeal Syndrome Type II ” as your search term in the Rare Disease Database.)Trichorhinophalangeal Syndrome Type III (TRPS3), also known as Sugio-Kajii Syndrome, is a rare inherited disorder with symptoms and physical features similar to those associated with Trichorhinophalangeal Syndromes Type I (TRPS1) and Type II (TRPS2). Affected individuals typically exhibit a rounded (bulbous) or “beaked” nose; thin, sparse hair; short stature; and/or abnormally short fingers and toes (brachydactyly). Other abnormalities may include underdeveloped (hypoplastic) jaws, dental anomalies, and/or a pointed chin. The shortness of the fingers and toes is markedly more severe in TRPS3 than in TRPS1 and TRPS2. In addition, individuals with TRPS3 do not develop multiple bony growths on the surfaces of various bones of the body (exostoses) or exhibit mental retardation and excess (redundant) skin as do children with TRPS2. Most cases of Trichorhinophalangeal Syndrome Type III is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose “Trichorhinophalangeal Syndrome Type III” as your search term in the Rare Disease Database.) The following disorder may be associated with Trichorhinophalangeal Syndrome Type I as a secondary characteristic. It is not necessary for a differential diagnosis: Legg-Calve-Perthes Disease is a rare disorder characterized by degeneration of the end portions of the thigh bones (capital femoral epiphyseal osteonecrosis). Onset may be between the ages of six and 12 years and typically begins as mild aching in the hips followed by impaired ability to move the affected leg. Pain in the hips may become more intense over time and muscle spasms may also develop. In most cases, the pain subsides without intervention (spontaneously). In some cases, the thigh bone may become shorter than normal, causing a noticeable limp and possibly resulting in short stature. (For more information on this disorder, choose “Legg Calve Perthes” as your search term in the Rare Disease Database.)
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Related disorders of Trichorhinophalangeal Syndrome Type I. Symptoms of the following disorders can be similar to those of Trichorhinophalangeal Syndrome Type I. Comparisons may be useful for a differential diagnosis: Trichorhinophalangeal Syndrome Type II, also known as Langer-Giedion Syndrome, is an extremely rare inherited disorder that has many of the same symptoms and physical features associated with Trichorhinophalangeal Syndrome Type I. These may include a rounded (bulbous) nose; a long, prominent groove (philtrum) of the upper lip; thin, sparse scalp hair; abnormally short fingers and toes (brachydactyly); and/or short stature. In addition, a child with Trichorhinophalangeal Syndrome Type II may exhibit an abnormally small head (microcephaly), excess (redundant) skin, and/or multiple bony growths on various bones of the body (exostoses). In some cases, mental retardation may also be present. Most cases of Trichorhinophalangeal Syndrome Type II occur randomly (sporadically) and are due to the absence of genetic material (chromosomal deletions) on chromsome 8 at the same site in Trichorhinophalangeal Syndrome Type I. (For more information on this disorder, choose ” Trichorhinophalangeal Syndrome Type II ” as your search term in the Rare Disease Database.)Trichorhinophalangeal Syndrome Type III (TRPS3), also known as Sugio-Kajii Syndrome, is a rare inherited disorder with symptoms and physical features similar to those associated with Trichorhinophalangeal Syndromes Type I (TRPS1) and Type II (TRPS2). Affected individuals typically exhibit a rounded (bulbous) or “beaked” nose; thin, sparse hair; short stature; and/or abnormally short fingers and toes (brachydactyly). Other abnormalities may include underdeveloped (hypoplastic) jaws, dental anomalies, and/or a pointed chin. The shortness of the fingers and toes is markedly more severe in TRPS3 than in TRPS1 and TRPS2. In addition, individuals with TRPS3 do not develop multiple bony growths on the surfaces of various bones of the body (exostoses) or exhibit mental retardation and excess (redundant) skin as do children with TRPS2. Most cases of Trichorhinophalangeal Syndrome Type III is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose “Trichorhinophalangeal Syndrome Type III” as your search term in the Rare Disease Database.) The following disorder may be associated with Trichorhinophalangeal Syndrome Type I as a secondary characteristic. It is not necessary for a differential diagnosis: Legg-Calve-Perthes Disease is a rare disorder characterized by degeneration of the end portions of the thigh bones (capital femoral epiphyseal osteonecrosis). Onset may be between the ages of six and 12 years and typically begins as mild aching in the hips followed by impaired ability to move the affected leg. Pain in the hips may become more intense over time and muscle spasms may also develop. In most cases, the pain subsides without intervention (spontaneously). In some cases, the thigh bone may become shorter than normal, causing a noticeable limp and possibly resulting in short stature. (For more information on this disorder, choose “Legg Calve Perthes” as your search term in the Rare Disease Database.)
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Diagnosis of Trichorhinophalangeal Syndrome Type I
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The diagnosis of TRPS1 may be suspected upon identification of characteristic physical features (e.g., rounded [bulbous] nose; thin, sparse hair; etc.). The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and X-ray studies of the skeleton that reveal distinctive abnormalities of the hands and feet (e.g., epiphyseal coning). Molecular genetic testing can reveal mutations of the TRPS1 gene.
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Diagnosis of Trichorhinophalangeal Syndrome Type I. The diagnosis of TRPS1 may be suspected upon identification of characteristic physical features (e.g., rounded [bulbous] nose; thin, sparse hair; etc.). The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and X-ray studies of the skeleton that reveal distinctive abnormalities of the hands and feet (e.g., epiphyseal coning). Molecular genetic testing can reveal mutations of the TRPS1 gene.
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Therapies of Trichorhinophalangeal Syndrome Type I
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TreatmentThe treatment of TRPS1 is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, speech pathologists, orthopedic surgeons, physicians who evaluate and treat skin problems (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Specific therapies for the treatment of TRPS1 are symptomatic and supportive. Various orthopedic techniques, including surgery, may be performed to help treat and/or correct skeletal abnormalities. Additional therapeutic and/or supportive measures may be necessary in some cases.Genetic counseling may be of benefit for affected individuals and their families.
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Therapies of Trichorhinophalangeal Syndrome Type I. TreatmentThe treatment of TRPS1 is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, speech pathologists, orthopedic surgeons, physicians who evaluate and treat skin problems (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Specific therapies for the treatment of TRPS1 are symptomatic and supportive. Various orthopedic techniques, including surgery, may be performed to help treat and/or correct skeletal abnormalities. Additional therapeutic and/or supportive measures may be necessary in some cases.Genetic counseling may be of benefit for affected individuals and their families.
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Overview of Trichorhinophalangeal Syndrome Type II
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Trichorhinophalangeal syndrome type II (TRPS2), also known as Langer-Giedion syndrome, is an extremely rare inherited multisystem disorder. TRPS2 is characterized by fine, thin hair; unusual facial features; progressive growth retardation resulting in short stature (dwarfism); abnormally short fingers and toes (brachydactyly); “cone-shaped” formation of the “growing ends” of certain bones (epiphyseal coning); and/or development of multiple bony growths (exostoses) projecting outward from the surfaces of various bones of the body. In addition, affected individuals may exhibit unusually flexible (hyperextensible) joints, diminished muscle tone (hypotonia), excess folds of skin (redundant skin), and/or discolored elevated spots on the skin (maculopapular nevi). Affected individuals may also exhibit mild to severe mental retardation, hearing loss (sensorineural deafness), and/or delayed speech development. The range and severity of symptoms varies greatly from case to case. TRPS2 is due to the absence of genetic material (chromosomal deletions) on chromosome 8. The size of the deletion varies from case to case.
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Overview of Trichorhinophalangeal Syndrome Type II. Trichorhinophalangeal syndrome type II (TRPS2), also known as Langer-Giedion syndrome, is an extremely rare inherited multisystem disorder. TRPS2 is characterized by fine, thin hair; unusual facial features; progressive growth retardation resulting in short stature (dwarfism); abnormally short fingers and toes (brachydactyly); “cone-shaped” formation of the “growing ends” of certain bones (epiphyseal coning); and/or development of multiple bony growths (exostoses) projecting outward from the surfaces of various bones of the body. In addition, affected individuals may exhibit unusually flexible (hyperextensible) joints, diminished muscle tone (hypotonia), excess folds of skin (redundant skin), and/or discolored elevated spots on the skin (maculopapular nevi). Affected individuals may also exhibit mild to severe mental retardation, hearing loss (sensorineural deafness), and/or delayed speech development. The range and severity of symptoms varies greatly from case to case. TRPS2 is due to the absence of genetic material (chromosomal deletions) on chromosome 8. The size of the deletion varies from case to case.
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Symptoms of Trichorhinophalangeal Syndrome Type II
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The range and severity of symptoms varies among individuals with trichorhinophalangeal syndrome type II. Affected individuals will not have all of the symptoms listed below. The most common symptoms include fine, thin hair; unusual facial features; short stature; abnormalities of the hands and feet; and/or development of multiple bony growths (exostoses) projecting outward from the surfaces of various bones of the body. Additional characteristic abnormalities may include mental retardation, diminished muscle tone (hypotonia), and/or skin abnormalities. Affected infants may exhibit markedly thin, sparse hair at birth (congenital); the hair may also be abnormally brittle and/or may grow slowly. Affected individuals may lose most or all of their scalp hair (alopecia) at a young age, in some cases, by the second decade of life. Infants with TRPS2 may also have abnormalities of the head and facial (craniofacial) area including a condition known as microcephaly, which indicates that the head circumference is smaller than would be expected for age and sex. Additional features may include an abnormally large, rounded (bulbous) nose with a broad nasal bridge and thick wide nostrils (tented alae); large, protruding ears; and/or an abnormally small jaw (micrognathia) that may be displaced father back than normal (retrognathia). Affected infants may also exhibit a prominent, elongated groove in the upper lip (philtrum); a thin upper lip that may droop; deep-set eyes; widely spaced eyes (ocular hyperterlorism); and/or deviation of one eye away from the other (exotropia). In some cases, children with TRPS2 may also have dental abnormalities such as extra teeth (supernumerary central incisors) and/or absence of certain teeth. During infancy, growth delays (retardation) may also be present. Growth retardation is typically progressive, resulting in short stature (dwarfism). In most cases, individuals with TRPS2 may also have abnormally short fingers and toes (brachydactyly), resulting, in part, from “cone-shaped” development of the “growing ends” of certain bones in the hands and feet (epiphyseal coning). In addition, the nails may be thin and brittle and, in some cases, the fifth fingers may be abnormally bent (clinodactyly). As affected individuals age, they may develop numerous bony growths (exostoses) that may project outward from the surface of various bones (e.g., pelvis, long bones, shoulder blade) in the body. In some cases, the development of multiple exostoses may result in compression of the spinal cord, certain nerves, and/or blood vessels; unequal (asymmetric) growth of the limbs; and/or limitations in movements. In addition, some affected individuals may be abnormally prone to bone fractures. Additional skeletal abnormalities may also be present including thin, narrow ribs; unusual “wing-like” shoulder blades (winged scapula); webbing (syndactyly) of certain fingers and toes; and/or abnormalities of the spinal column including sideways curvature of the spine (scoliosis). Some individuals with TRPS2 may develop hip problems similar to those experienced by people with Legg-Calve-Perthes disease including progressive degeneration of the end portion (head) of the thighbone (capital femoral epiphyseal osteonecrosis). (For more information on Legg-Calve-Perthes disease, see the Related Disorders section of this report.) In many affected infants, mild to severe mental retardation is present at birth. In other cases, mental retardation may not become obvious until late infancy or childhood. However, in approximately 25 percent of affected individuals, intelligence may be normal. Affected newborns may also exhibit additional physical abnormalities including excess (redundant) skin, numerous discolored elevated spots on the skin (maculopapular nevi), diminished muscle tone (hypotonia), and/or abnormally flexible (hyperextensible) joints. As affected children age, excess skin may appear tighter and muscle tone may improve; however, skin lesions may become more numerous. Affected infants may also exhibit hearing loss (sensorineural deafness) and delays in the development of speech. In some cases, individuals affected with TRPS2 may be susceptible to frequent respiratory infections. In some cases, affected individuals may have additional abnormalities affecting the genito-urinary tract (e.g., accumulation of fluid in the uterus (hydrometrocolpos) and blood in the uterus (hematometra) in females, ureteral reflux, etc.).
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Symptoms of Trichorhinophalangeal Syndrome Type II. The range and severity of symptoms varies among individuals with trichorhinophalangeal syndrome type II. Affected individuals will not have all of the symptoms listed below. The most common symptoms include fine, thin hair; unusual facial features; short stature; abnormalities of the hands and feet; and/or development of multiple bony growths (exostoses) projecting outward from the surfaces of various bones of the body. Additional characteristic abnormalities may include mental retardation, diminished muscle tone (hypotonia), and/or skin abnormalities. Affected infants may exhibit markedly thin, sparse hair at birth (congenital); the hair may also be abnormally brittle and/or may grow slowly. Affected individuals may lose most or all of their scalp hair (alopecia) at a young age, in some cases, by the second decade of life. Infants with TRPS2 may also have abnormalities of the head and facial (craniofacial) area including a condition known as microcephaly, which indicates that the head circumference is smaller than would be expected for age and sex. Additional features may include an abnormally large, rounded (bulbous) nose with a broad nasal bridge and thick wide nostrils (tented alae); large, protruding ears; and/or an abnormally small jaw (micrognathia) that may be displaced father back than normal (retrognathia). Affected infants may also exhibit a prominent, elongated groove in the upper lip (philtrum); a thin upper lip that may droop; deep-set eyes; widely spaced eyes (ocular hyperterlorism); and/or deviation of one eye away from the other (exotropia). In some cases, children with TRPS2 may also have dental abnormalities such as extra teeth (supernumerary central incisors) and/or absence of certain teeth. During infancy, growth delays (retardation) may also be present. Growth retardation is typically progressive, resulting in short stature (dwarfism). In most cases, individuals with TRPS2 may also have abnormally short fingers and toes (brachydactyly), resulting, in part, from “cone-shaped” development of the “growing ends” of certain bones in the hands and feet (epiphyseal coning). In addition, the nails may be thin and brittle and, in some cases, the fifth fingers may be abnormally bent (clinodactyly). As affected individuals age, they may develop numerous bony growths (exostoses) that may project outward from the surface of various bones (e.g., pelvis, long bones, shoulder blade) in the body. In some cases, the development of multiple exostoses may result in compression of the spinal cord, certain nerves, and/or blood vessels; unequal (asymmetric) growth of the limbs; and/or limitations in movements. In addition, some affected individuals may be abnormally prone to bone fractures. Additional skeletal abnormalities may also be present including thin, narrow ribs; unusual “wing-like” shoulder blades (winged scapula); webbing (syndactyly) of certain fingers and toes; and/or abnormalities of the spinal column including sideways curvature of the spine (scoliosis). Some individuals with TRPS2 may develop hip problems similar to those experienced by people with Legg-Calve-Perthes disease including progressive degeneration of the end portion (head) of the thighbone (capital femoral epiphyseal osteonecrosis). (For more information on Legg-Calve-Perthes disease, see the Related Disorders section of this report.) In many affected infants, mild to severe mental retardation is present at birth. In other cases, mental retardation may not become obvious until late infancy or childhood. However, in approximately 25 percent of affected individuals, intelligence may be normal. Affected newborns may also exhibit additional physical abnormalities including excess (redundant) skin, numerous discolored elevated spots on the skin (maculopapular nevi), diminished muscle tone (hypotonia), and/or abnormally flexible (hyperextensible) joints. As affected children age, excess skin may appear tighter and muscle tone may improve; however, skin lesions may become more numerous. Affected infants may also exhibit hearing loss (sensorineural deafness) and delays in the development of speech. In some cases, individuals affected with TRPS2 may be susceptible to frequent respiratory infections. In some cases, affected individuals may have additional abnormalities affecting the genito-urinary tract (e.g., accumulation of fluid in the uterus (hydrometrocolpos) and blood in the uterus (hematometra) in females, ureteral reflux, etc.).
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Causes of Trichorhinophalangeal Syndrome Type II
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With few exceptions, most cases of trichorhinophalangeal syndrome type II are the result of the absence of genetic material (chromosome deletions). Rarely, those with the syndrome have children. Two documented cases show that the deletion is inherited in an autosomal dominant manner. 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.TRPS2 results from deletions (mutations) and loss of function in several adjacent genes (contiguous gene syndrome) located on the long arm (q) of chromosome 8 (8q24.11-q24.13). 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 8q24.11-q24.13” refers to bands 24.11-24.13 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Researchers have located two of the genes (i.e., TRPS1 and EXT1 genes) responsible for TRPS2. These genes are located on chromosome 8 between bands q24.11-q24.13.
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Causes of Trichorhinophalangeal Syndrome Type II. With few exceptions, most cases of trichorhinophalangeal syndrome type II are the result of the absence of genetic material (chromosome deletions). Rarely, those with the syndrome have children. Two documented cases show that the deletion is inherited in an autosomal dominant manner. 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.TRPS2 results from deletions (mutations) and loss of function in several adjacent genes (contiguous gene syndrome) located on the long arm (q) of chromosome 8 (8q24.11-q24.13). 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 8q24.11-q24.13” refers to bands 24.11-24.13 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Researchers have located two of the genes (i.e., TRPS1 and EXT1 genes) responsible for TRPS2. These genes are located on chromosome 8 between bands q24.11-q24.13.
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Affects of Trichorhinophalangeal Syndrome Type II
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Trichorhinophalangeal syndrome type II is an extremely rare disorder that appears to affect males approximately three times as frequently as females. More than 60 cases have been reported in the medical literature. Many symptoms associated with the disorder (e.g., excess skin, abnormal facial features) may be apparent at birth. Changes affecting the “growing ends” (epiphyses) of certain bones may not be apparent on x-rays until approximately three years of age. The development of bony growths that project outward from the surfaces of certain bones (multiple exostoses) are usually apparent by the age of three or five years; however, in some cases, they may be present as early as the first year of life.
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Affects of Trichorhinophalangeal Syndrome Type II. Trichorhinophalangeal syndrome type II is an extremely rare disorder that appears to affect males approximately three times as frequently as females. More than 60 cases have been reported in the medical literature. Many symptoms associated with the disorder (e.g., excess skin, abnormal facial features) may be apparent at birth. Changes affecting the “growing ends” (epiphyses) of certain bones may not be apparent on x-rays until approximately three years of age. The development of bony growths that project outward from the surfaces of certain bones (multiple exostoses) are usually apparent by the age of three or five years; however, in some cases, they may be present as early as the first year of life.
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Related disorders of Trichorhinophalangeal Syndrome Type II
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Symptoms of the following disorders can be similar to those of Trichorhinophalangeal Syndrome Type II. Comparisons may be useful for a differential diagnosis: Trichorhinophalangeal Syndrome Type I (TRPS1) is an extremely rare inherited multisystem disorder characterized by fine, thin hair; unusual facial features; abnormalities of the fingers and/or toes; and multiple abnormalities of the “growing ends” (epiphyses) of the bones, especially in the hands and feet. Characteristic facial features may include a rounded (bulbous) “pear-shaped” nose, an abnormally small jaw (micrognathia), dental anomalies, and/or unusually large (prominent) ears. In most cases, the fingers and/or toes may be abnormally short (brachydactyly) and curved. In addition, affected individuals may exhibit short stature (dwarfism). Individuals with TRPS1 do not exhibit multiple bony growths (exostoses), excess skin, or mental retardation, symptoms that are common in TRPS2. Trichorhinophalangeal Syndrome Type I has autosomal dominant inheritance. (For more information on this disorder, choose “Trichorhinophalangeal Syndrome Type I” as your search term in the Rare Disease Database.) Trichorhinophalangeal Syndrome Type III (TRPS3), also known as Sugio-Kajii Syndrome, is an extremely rare inherited disorder that is similar to TRPS1 and TRPS2. Affected individuals typically have thin, sparse hair; unusual facial features; and abnormally short fingers and toes (brachydactyly). Characteristic facial features may include a rounded (bulbous) or “beaked” nose, a high forehead, dental anomalies, underdeveloped (hypoplastic) jaws, and/or a pointed chin. Abnormal shortness of the fingers and toes is much more pronounced in children with TRPS3 than in those with TRPS1. Children with TRPS3 do not exhibit bony growths projecting outward from the surface of various bones of the body (multiple exostoses), excess skin, or mental retardation, symptoms that are common in TRPS2. Trichorhinophalangeal Syndrome Type III is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose “Trichorhinophalangeal Syndrome Type III” as your search term in the Rare Disease Database.) Multiple Exostoses is a rare disorder characterized by multiple bony growths (multiple exostoses) on the surface of various bones of the body. These bony growths continue to form until shortly after puberty and may cause deformities, particularly of the ankle, knee, and wrist. In some cases, affected individuals may also have abnormally short bones in the fingers (metacarpals). Multiple Exostoses may result in short stature and/or compression of the spinal cord and/or various nerves. Multiple Exostoses has autosomal dominant inheritance. (For more information on this disorder, choose “Multiple Exostoses” as your search term in the Rare Disease Database.) Fibrodysplasia Ossificans Progressiva (FOP) is a very rare inherited connective tissue disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification), such as the ligaments, tendons, and muscles. Major symptoms may include skeletal malformations and/or abnormally short and malformed toes and fingers. The abnormal development of bone leads to stiffness in affected areas and may also limit movements in affected joints (e.g., knees, wrists, shoulders, spine, neck, etc.). Fibrodysplasia Ossificans Progressiva usually begins during early childhood and progresses throughout life. Most cases of FOP occur randomly (sporadically). In the few cases where affected individuals have had children, inheritance has been in an autosomal dominant manner. (For more information on this disorder, choose “Fibrodysplasia Ossificans Progressiva” as your search term in the Rare Disease Database.) The following disorder may be associated with Trichorhinophalangeal Syndrome as a secondary characteristic. It is not necessary for a differential diagnosis: Legg-Calve-Perthes Disease is a rare disorder characterized by degeneration of the end portions of the thigh bones (capital femoral epiphyseal osteonecrosis). Onset may be between the ages of six and 12 years and typically begins as mild aching in the hips followed by impaired ability to move the affected leg(s). Pain in the hips may become more intense over time and muscle spasms may also develop. In most cases, the pain subsides without intervention (spontaneously). In some cases, the thigh bone may become shorter than normal, causing a noticeable limp. The exact cause of Legg-Calve-Perthes Disease is not known. (For more information on this disorder, choose “Legg-Calve-Perthes” as your search term in the Rare Disease Database.)
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Related disorders of Trichorhinophalangeal Syndrome Type II. Symptoms of the following disorders can be similar to those of Trichorhinophalangeal Syndrome Type II. Comparisons may be useful for a differential diagnosis: Trichorhinophalangeal Syndrome Type I (TRPS1) is an extremely rare inherited multisystem disorder characterized by fine, thin hair; unusual facial features; abnormalities of the fingers and/or toes; and multiple abnormalities of the “growing ends” (epiphyses) of the bones, especially in the hands and feet. Characteristic facial features may include a rounded (bulbous) “pear-shaped” nose, an abnormally small jaw (micrognathia), dental anomalies, and/or unusually large (prominent) ears. In most cases, the fingers and/or toes may be abnormally short (brachydactyly) and curved. In addition, affected individuals may exhibit short stature (dwarfism). Individuals with TRPS1 do not exhibit multiple bony growths (exostoses), excess skin, or mental retardation, symptoms that are common in TRPS2. Trichorhinophalangeal Syndrome Type I has autosomal dominant inheritance. (For more information on this disorder, choose “Trichorhinophalangeal Syndrome Type I” as your search term in the Rare Disease Database.) Trichorhinophalangeal Syndrome Type III (TRPS3), also known as Sugio-Kajii Syndrome, is an extremely rare inherited disorder that is similar to TRPS1 and TRPS2. Affected individuals typically have thin, sparse hair; unusual facial features; and abnormally short fingers and toes (brachydactyly). Characteristic facial features may include a rounded (bulbous) or “beaked” nose, a high forehead, dental anomalies, underdeveloped (hypoplastic) jaws, and/or a pointed chin. Abnormal shortness of the fingers and toes is much more pronounced in children with TRPS3 than in those with TRPS1. Children with TRPS3 do not exhibit bony growths projecting outward from the surface of various bones of the body (multiple exostoses), excess skin, or mental retardation, symptoms that are common in TRPS2. Trichorhinophalangeal Syndrome Type III is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose “Trichorhinophalangeal Syndrome Type III” as your search term in the Rare Disease Database.) Multiple Exostoses is a rare disorder characterized by multiple bony growths (multiple exostoses) on the surface of various bones of the body. These bony growths continue to form until shortly after puberty and may cause deformities, particularly of the ankle, knee, and wrist. In some cases, affected individuals may also have abnormally short bones in the fingers (metacarpals). Multiple Exostoses may result in short stature and/or compression of the spinal cord and/or various nerves. Multiple Exostoses has autosomal dominant inheritance. (For more information on this disorder, choose “Multiple Exostoses” as your search term in the Rare Disease Database.) Fibrodysplasia Ossificans Progressiva (FOP) is a very rare inherited connective tissue disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification), such as the ligaments, tendons, and muscles. Major symptoms may include skeletal malformations and/or abnormally short and malformed toes and fingers. The abnormal development of bone leads to stiffness in affected areas and may also limit movements in affected joints (e.g., knees, wrists, shoulders, spine, neck, etc.). Fibrodysplasia Ossificans Progressiva usually begins during early childhood and progresses throughout life. Most cases of FOP occur randomly (sporadically). In the few cases where affected individuals have had children, inheritance has been in an autosomal dominant manner. (For more information on this disorder, choose “Fibrodysplasia Ossificans Progressiva” as your search term in the Rare Disease Database.) The following disorder may be associated with Trichorhinophalangeal Syndrome as a secondary characteristic. It is not necessary for a differential diagnosis: Legg-Calve-Perthes Disease is a rare disorder characterized by degeneration of the end portions of the thigh bones (capital femoral epiphyseal osteonecrosis). Onset may be between the ages of six and 12 years and typically begins as mild aching in the hips followed by impaired ability to move the affected leg(s). Pain in the hips may become more intense over time and muscle spasms may also develop. In most cases, the pain subsides without intervention (spontaneously). In some cases, the thigh bone may become shorter than normal, causing a noticeable limp. The exact cause of Legg-Calve-Perthes Disease is not known. (For more information on this disorder, choose “Legg-Calve-Perthes” as your search term in the Rare Disease Database.)
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Diagnosis of Trichorhinophalangeal Syndrome Type II
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The diagnosis of trichorhinophalangeal syndrome type II may be suspected at birth in some cases by a thorough clinical evaluation and identification of characteristic features. Abnormalities that are usually present at birth include unusual facial features including a large, rounded (bulbous) nose, thin, sparse hair and/or excess skin. Molecular genetic testing can confirm a diagnosis of TRPS2 by identifying mutations of the TRPS1 or EXT1 genes.As affected individuals age, specialized imaging techniques (e.g., various x-ray methods) may be used to identify "cone-shaped" development of the end portions of certain bones (epiphyseal coning) and/or the formation of numerous bony growths (exostoses) projecting outward from the surfaces of various bones in the body. Mental retardation, hearing loss, and/or speech delays may not be detectable until affected infants grow older.
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Diagnosis of Trichorhinophalangeal Syndrome Type II. The diagnosis of trichorhinophalangeal syndrome type II may be suspected at birth in some cases by a thorough clinical evaluation and identification of characteristic features. Abnormalities that are usually present at birth include unusual facial features including a large, rounded (bulbous) nose, thin, sparse hair and/or excess skin. Molecular genetic testing can confirm a diagnosis of TRPS2 by identifying mutations of the TRPS1 or EXT1 genes.As affected individuals age, specialized imaging techniques (e.g., various x-ray methods) may be used to identify "cone-shaped" development of the end portions of certain bones (epiphyseal coning) and/or the formation of numerous bony growths (exostoses) projecting outward from the surfaces of various bones in the body. Mental retardation, hearing loss, and/or speech delays may not be detectable until affected infants grow older.
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Therapies of Trichorhinophalangeal Syndrome Type II
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TreatmentThe treatment of TRPS2 is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), orthopedic surgeons, speech pathologists, physicians who specialize in assessing and treating hearing problems (audiologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.In some cases, treatment may include surgical removal of multiple exostoses that cause pain, result in compression of nerves, hinder proper development of limbs, and/or cause impairment of certain movements. Physical therapy in combination with other supportive measures may also improve an affected individual's ability to perform certain movements more easily. Hearing aids may be used to help treat significant hearing loss. In addition, physicians may regularly monitor affected individuals and recommend preventative measures for those who may be prone to repeated respiratory infections.Early intervention is important in ensuring that children with TRPS2 reach their potential. Special services that may be beneficial to affected children include special remedial education, speech therapy, and other medical, social, and/or vocational services.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Therapies of Trichorhinophalangeal Syndrome Type II. TreatmentThe treatment of TRPS2 is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), orthopedic surgeons, speech pathologists, physicians who specialize in assessing and treating hearing problems (audiologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.In some cases, treatment may include surgical removal of multiple exostoses that cause pain, result in compression of nerves, hinder proper development of limbs, and/or cause impairment of certain movements. Physical therapy in combination with other supportive measures may also improve an affected individual's ability to perform certain movements more easily. Hearing aids may be used to help treat significant hearing loss. In addition, physicians may regularly monitor affected individuals and recommend preventative measures for those who may be prone to repeated respiratory infections.Early intervention is important in ensuring that children with TRPS2 reach their potential. Special services that may be beneficial to affected children include special remedial education, speech therapy, and other medical, social, and/or vocational services.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Overview of Trichorhinophalangeal Syndrome Type III
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Trichorhinophalangeal syndrome type III (TRPS3), also known as Sugio-Kajii syndrome, is an extremely rare inherited multisystem disorder. TRPS3 is characterized by fine, thin light-colored hair; unusual facial features; abnormalities of the fingers and/or toes; and multiple abnormalities of the “growing ends” (epiphyses) of the bones (skeletal dysplasia), especially in the hands and feet. Characteristic facial features may include a pear-shaped or rounded (bulbous) nose; an abnormally long prominent groove (philtrum) in the upper lip; and/or abnormalities such as delayed eruption of teeth. In addition, affected individuals also exhibit severe shortening of the fingers and toes (brachydactyly) due to improper development of bones in the hands and feet (metacarpophalangeal shortening). Additional features often include short stature (dwarfism) and/or additional skeletal abnormalities. The range and severity of symptoms may vary from case to case. TRPS3 is thought to have autosomal dominant inheritance.
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Overview of Trichorhinophalangeal Syndrome Type III. Trichorhinophalangeal syndrome type III (TRPS3), also known as Sugio-Kajii syndrome, is an extremely rare inherited multisystem disorder. TRPS3 is characterized by fine, thin light-colored hair; unusual facial features; abnormalities of the fingers and/or toes; and multiple abnormalities of the “growing ends” (epiphyses) of the bones (skeletal dysplasia), especially in the hands and feet. Characteristic facial features may include a pear-shaped or rounded (bulbous) nose; an abnormally long prominent groove (philtrum) in the upper lip; and/or abnormalities such as delayed eruption of teeth. In addition, affected individuals also exhibit severe shortening of the fingers and toes (brachydactyly) due to improper development of bones in the hands and feet (metacarpophalangeal shortening). Additional features often include short stature (dwarfism) and/or additional skeletal abnormalities. The range and severity of symptoms may vary from case to case. TRPS3 is thought to have autosomal dominant inheritance.
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Symptoms of Trichorhinophalangeal Syndrome Type III
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The symptoms of trichorhinophalangeal syndrome type III may vary in range and severity from case to case. Common symptoms include fine, thin light-colored hair; unusual facial features; multiple abnormalities affecting the “growing ends” (epiphyses) of the certain bones, particularly those in the hands and feet; severe shortening of the fingers and toes (brachydactyly); and/or additional skeletal abnormalities. Infants with TRPS3 may exhibit markedly thin, sparse scalp hair at birth (congenital). The hair may also be usually fine and brittle. Affected infants also have several characteristic facial features. These may include a pear-shaped or rounded (bulbous) nose with small, underdeveloped nostrils (hypoplastic alae nasi); an abnormally long broad groove (philtrum) on the upper lip as well as a long, protruding upper lip; underdeveloped cheek bones (malar hypoplasia); and/or an abnormally prominent upper jaw bone (maxilla). Affected individuals may also exhibit dental abnormalities including delayed eruption and/or abnormal positioning (malocclusion) of the teeth. In most cases, individuals with TRPS3 have several abnormalities of the hands and feet. Affected individuals may exhibit severe shortening of the fingers and toes (brachydactyly) due, in part, to incomplete development of bones in the hands (e.g., metacarpals), the feet (e.g., metatarsals), and the fingers and toes (phalanges). In addition, the “growing ends” (epiphyses) of the bones of the fingers and toes may be abnormally “cone-shaped” and may harden (ossify) before growth is complete (premature fusion). Most affected individuals exhibit permanent fixation of the fingers in a bent position (clinodactyly). Affected individuals may also exhibit additional skeletal abnormalities including short stature, inflammation of the bone and cartilage in the spinal column (osteochondritis), abnormal sideways curvature of the spine (thoracic scoliosis), abnormal prominence of the breast bone (pectus carinatum), and/or limited movements of certain joints. In addition, some females affected by this disorder may exhibit abnormally broad hip development with advancing age.
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Symptoms of Trichorhinophalangeal Syndrome Type III. The symptoms of trichorhinophalangeal syndrome type III may vary in range and severity from case to case. Common symptoms include fine, thin light-colored hair; unusual facial features; multiple abnormalities affecting the “growing ends” (epiphyses) of the certain bones, particularly those in the hands and feet; severe shortening of the fingers and toes (brachydactyly); and/or additional skeletal abnormalities. Infants with TRPS3 may exhibit markedly thin, sparse scalp hair at birth (congenital). The hair may also be usually fine and brittle. Affected infants also have several characteristic facial features. These may include a pear-shaped or rounded (bulbous) nose with small, underdeveloped nostrils (hypoplastic alae nasi); an abnormally long broad groove (philtrum) on the upper lip as well as a long, protruding upper lip; underdeveloped cheek bones (malar hypoplasia); and/or an abnormally prominent upper jaw bone (maxilla). Affected individuals may also exhibit dental abnormalities including delayed eruption and/or abnormal positioning (malocclusion) of the teeth. In most cases, individuals with TRPS3 have several abnormalities of the hands and feet. Affected individuals may exhibit severe shortening of the fingers and toes (brachydactyly) due, in part, to incomplete development of bones in the hands (e.g., metacarpals), the feet (e.g., metatarsals), and the fingers and toes (phalanges). In addition, the “growing ends” (epiphyses) of the bones of the fingers and toes may be abnormally “cone-shaped” and may harden (ossify) before growth is complete (premature fusion). Most affected individuals exhibit permanent fixation of the fingers in a bent position (clinodactyly). Affected individuals may also exhibit additional skeletal abnormalities including short stature, inflammation of the bone and cartilage in the spinal column (osteochondritis), abnormal sideways curvature of the spine (thoracic scoliosis), abnormal prominence of the breast bone (pectus carinatum), and/or limited movements of certain joints. In addition, some females affected by this disorder may exhibit abnormally broad hip development with advancing age.
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Causes of Trichorhinophalangeal Syndrome Type III
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Trichorhinophalangeal syndrome type III is inherited in an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.Most cases of TRPS3 occur due to changes or disruptions (mutations) of the TRPS1 located on the long arm of chromosome 8 (8q24.12). 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 8q24.12” refers to band 24.12 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome. The physical findings and symptoms associated with TRPS3 may vary greatly from case to case (variable expressivity).
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Causes of Trichorhinophalangeal Syndrome Type III. Trichorhinophalangeal syndrome type III is inherited in an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.Most cases of TRPS3 occur due to changes or disruptions (mutations) of the TRPS1 located on the long arm of chromosome 8 (8q24.12). 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 8q24.12” refers to band 24.12 on the long arm of chromosome 8. The numbered bands specify the location of the thousands of genes that are present on each chromosome. The physical findings and symptoms associated with TRPS3 may vary greatly from case to case (variable expressivity).
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Trichorhinophalangeal Syndrome Type III
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nord_1228_3
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Affects of Trichorhinophalangeal Syndrome Type III
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Trichorhinophalangeal syndrome type III is an extremely rare disorder that, in theory, affects males and females in equal numbers. However, of the reported cases, most affected individuals have been female. Approximately 15 cases have been reported in the medical literature.
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Affects of Trichorhinophalangeal Syndrome Type III. Trichorhinophalangeal syndrome type III is an extremely rare disorder that, in theory, affects males and females in equal numbers. However, of the reported cases, most affected individuals have been female. Approximately 15 cases have been reported in the medical literature.
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Trichorhinophalangeal Syndrome Type III
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