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nord_1114_2
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Causes of Short QT Syndrome
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While usually assumed to be inheritable, SQTS cases in which a familiar history is absent may be caused by a spontaneous mutation during embryonic development (known as a de novo mutation). Moreover, not all SQTS patients have an identifiable mutation.Acquired SQTS may be associated with hypercalcemia, hyperkalaemia, acidosis and with some drugs effects. Before delving into the mode of inheritance of SQTS, it is important to remember that a gene is a coding sequence present in chromosomes with the necessary information to produce a specific protein. The resulting gene product may play essential roles in the correct function of the body. A mutation may provoke an abnormal loss- or gain-of-function of the encoded protein. Consequently, the dysfunction of the resulting protein will be the initial trigger of the chain of events that result in a syndrome like SQTS.SQTS is considered to be a genetic disease caused by mutations in multiple genes and follows autosomal dominant inheritance; that is, it occurs when a single copy of a non- or hyper-working gene is inherited from either parent. However, follow-up of patients with SQTS showed that only 20 to 30% may be explained by mutations in genes encoding potassium or calcium channels.To date, of thirty-two variants described in the literature, only nine mutations in three genes encoding potassium ion channels (KCNQ1, KCNH2 and KCNJ2) have been clearly associated with SQTS. Identified variants in potassium channels are gain-of-function mutations and each of the genes causes a different SQTS subtype: KCNH2 – SQTS1 [OMIM 609620], KCNQ1 – SQTS2 [OMIM 609621], and KCNJ2 – SQTS3 [OMIM 609622]. In these cases, the increased function of the potassium ion channels results in a faster than normal repolarization phase of the cardiac action potential, with the consequent shortening of the QTc interval. Genetic alterations in genes encoding calcium or sodium channels have not been demonstrated to lead to a clear diagnosis of SQTS. Nevertheless, several mutations in calcium channels responsible for depolarizing currents have been associated with the less prevalent forms of SQTS (SQTS4-6). For example, a genetic alteration with loss-of-function in the L-type calcium channel might yield a SQTS subtype (SQTS4) with an extremely low prevalence. As suggested, the reduced negative ionic current conducted by these mutated channels shortens the action potential and the QTc interval duration. The variants identified for the latter genes are also associated with Brugada syndrome, another channelopathy.
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Causes of Short QT Syndrome. While usually assumed to be inheritable, SQTS cases in which a familiar history is absent may be caused by a spontaneous mutation during embryonic development (known as a de novo mutation). Moreover, not all SQTS patients have an identifiable mutation.Acquired SQTS may be associated with hypercalcemia, hyperkalaemia, acidosis and with some drugs effects. Before delving into the mode of inheritance of SQTS, it is important to remember that a gene is a coding sequence present in chromosomes with the necessary information to produce a specific protein. The resulting gene product may play essential roles in the correct function of the body. A mutation may provoke an abnormal loss- or gain-of-function of the encoded protein. Consequently, the dysfunction of the resulting protein will be the initial trigger of the chain of events that result in a syndrome like SQTS.SQTS is considered to be a genetic disease caused by mutations in multiple genes and follows autosomal dominant inheritance; that is, it occurs when a single copy of a non- or hyper-working gene is inherited from either parent. However, follow-up of patients with SQTS showed that only 20 to 30% may be explained by mutations in genes encoding potassium or calcium channels.To date, of thirty-two variants described in the literature, only nine mutations in three genes encoding potassium ion channels (KCNQ1, KCNH2 and KCNJ2) have been clearly associated with SQTS. Identified variants in potassium channels are gain-of-function mutations and each of the genes causes a different SQTS subtype: KCNH2 – SQTS1 [OMIM 609620], KCNQ1 – SQTS2 [OMIM 609621], and KCNJ2 – SQTS3 [OMIM 609622]. In these cases, the increased function of the potassium ion channels results in a faster than normal repolarization phase of the cardiac action potential, with the consequent shortening of the QTc interval. Genetic alterations in genes encoding calcium or sodium channels have not been demonstrated to lead to a clear diagnosis of SQTS. Nevertheless, several mutations in calcium channels responsible for depolarizing currents have been associated with the less prevalent forms of SQTS (SQTS4-6). For example, a genetic alteration with loss-of-function in the L-type calcium channel might yield a SQTS subtype (SQTS4) with an extremely low prevalence. As suggested, the reduced negative ionic current conducted by these mutated channels shortens the action potential and the QTc interval duration. The variants identified for the latter genes are also associated with Brugada syndrome, another channelopathy.
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nord_1114_3
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Affects of Short QT Syndrome
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Many SQTS patients likely go undiagnosed or misdiagnosed, and determinations of SQTS incidence and prevalence are difficult due to limited data. Some have estimated the SQTS prevalence at less than 1 in 10,000. Others have suggested that SQTS shows a peak of incidence during the first year of life, age at which many SCD events occur and another peak in late adulthood.When an ECG is taken at rest, the QTc interval duration is longer in females than in males. In addition, data suggest that men with idiopathic ventricular fibrillation (i.e., ventricular fibrillation of an unknown cause) show a higher prevalence of short QT interval than healthy males. However, though there might be a slight male SQTS predominance, no conclusive data are yet published. In addition, there do not seem to be differences between males and females in the risk of experiencing cardiac disorders due to SQTS. Differences in terms of ethnic groups also have not been reported in the literature.
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Affects of Short QT Syndrome. Many SQTS patients likely go undiagnosed or misdiagnosed, and determinations of SQTS incidence and prevalence are difficult due to limited data. Some have estimated the SQTS prevalence at less than 1 in 10,000. Others have suggested that SQTS shows a peak of incidence during the first year of life, age at which many SCD events occur and another peak in late adulthood.When an ECG is taken at rest, the QTc interval duration is longer in females than in males. In addition, data suggest that men with idiopathic ventricular fibrillation (i.e., ventricular fibrillation of an unknown cause) show a higher prevalence of short QT interval than healthy males. However, though there might be a slight male SQTS predominance, no conclusive data are yet published. In addition, there do not seem to be differences between males and females in the risk of experiencing cardiac disorders due to SQTS. Differences in terms of ethnic groups also have not been reported in the literature.
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nord_1114_4
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Related disorders of Short QT Syndrome
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SQTS is classified among the “channelopathies” encompassing diseases caused by mutations in genes encoding ion channels. Opposite defects in the function of the products of one these genes may cause completely different diseases included in the same group. A case in point is the Andersen-Tawil syndrome (ATS). Loss-of-function mutations in KCNJ2 (gene encoding the potassium channel Kir2.1) provoke ATS type 1, while gain-of-function alterations in the same gene yield SQTS type 3. Similarly, loss-of-function mutations in KCNH2, which codes for HERG, result in long QT syndrome type 2, whereas gain-of-function mutations in the same gene result in SQTS type 1. The link between these channelopathies is the mutated gene causing each disease and its symptoms. However, the ECG findings that characterize each channelopathy are different and, for the most part, it is easy to differentiate among them. (For more information on these disorders (ATS, LQTSs, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia), choose the specific disorder name as your search term in the Rare Disease Database).
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Related disorders of Short QT Syndrome. SQTS is classified among the “channelopathies” encompassing diseases caused by mutations in genes encoding ion channels. Opposite defects in the function of the products of one these genes may cause completely different diseases included in the same group. A case in point is the Andersen-Tawil syndrome (ATS). Loss-of-function mutations in KCNJ2 (gene encoding the potassium channel Kir2.1) provoke ATS type 1, while gain-of-function alterations in the same gene yield SQTS type 3. Similarly, loss-of-function mutations in KCNH2, which codes for HERG, result in long QT syndrome type 2, whereas gain-of-function mutations in the same gene result in SQTS type 1. The link between these channelopathies is the mutated gene causing each disease and its symptoms. However, the ECG findings that characterize each channelopathy are different and, for the most part, it is easy to differentiate among them. (For more information on these disorders (ATS, LQTSs, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia), choose the specific disorder name as your search term in the Rare Disease Database).
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nord_1114_5
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Diagnosis of Short QT Syndrome
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Around 250 cases and nearly 150 families have been reported in the literature with SQTS. These numbers may not be entirely accurate, as there are difficulties diagnosing these patients. While the disease may be obvious in symptomatic patients, doubts may arise when dealing with asymptomatic patients, especially if they have no family history. In the past, SQTS was diagnosed if the QTc interval was 0.3 seconds or less. Nowadays, SQTS is suspected when the QTc interval duration is 0.34 seconds, a threshold under which a definitive diagnosis is established, even in the absence of symptoms. Furthermore, SQTS is also considered in patients with a QTc interval between 0.34 and 0.36 seconds plus one or more of the following signs: history of documented ventricular tachycardia or ventricular fibrillation in the absence of heart disease or reversible causes, family history of SQTS, family history of unexplained SCD at age ≤ 40 or a confirmed disease-causing mutation.To find a possible causative mutation, genetic screening must be carried out. However, it is important to note that the role of genetic testing is limited in SQTS as most patients who show symptoms currently have an unknown genetic cause. Nevertheless, according to current SQTS guidelines, genetic testing should be considered, and the candidate genes included in this test are: KCNH2, KCNQ1, KCNJ2, CACNA1C, and CACNB2b. In some cases, CACNA2D1, SCN5A and SLC4A3 genes are also analysed. If a causative mutation is found in a patient with SQTS, family members should be tested immediately to diagnose possible SQTS cases early.Importantly, since the ECG is a very useful and informative tool, findings such as a short QT interval, abnormal changes in the QT interval with heart rate, peaked and asymmetrical T waves (particularly in precordial leads), short (or absent) ST segments and paroxysmal episodes of atrial or ventricular fibrillation may facilitate the correct diagnosis of SQTS.
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Diagnosis of Short QT Syndrome. Around 250 cases and nearly 150 families have been reported in the literature with SQTS. These numbers may not be entirely accurate, as there are difficulties diagnosing these patients. While the disease may be obvious in symptomatic patients, doubts may arise when dealing with asymptomatic patients, especially if they have no family history. In the past, SQTS was diagnosed if the QTc interval was 0.3 seconds or less. Nowadays, SQTS is suspected when the QTc interval duration is 0.34 seconds, a threshold under which a definitive diagnosis is established, even in the absence of symptoms. Furthermore, SQTS is also considered in patients with a QTc interval between 0.34 and 0.36 seconds plus one or more of the following signs: history of documented ventricular tachycardia or ventricular fibrillation in the absence of heart disease or reversible causes, family history of SQTS, family history of unexplained SCD at age ≤ 40 or a confirmed disease-causing mutation.To find a possible causative mutation, genetic screening must be carried out. However, it is important to note that the role of genetic testing is limited in SQTS as most patients who show symptoms currently have an unknown genetic cause. Nevertheless, according to current SQTS guidelines, genetic testing should be considered, and the candidate genes included in this test are: KCNH2, KCNQ1, KCNJ2, CACNA1C, and CACNB2b. In some cases, CACNA2D1, SCN5A and SLC4A3 genes are also analysed. If a causative mutation is found in a patient with SQTS, family members should be tested immediately to diagnose possible SQTS cases early.Importantly, since the ECG is a very useful and informative tool, findings such as a short QT interval, abnormal changes in the QT interval with heart rate, peaked and asymmetrical T waves (particularly in precordial leads), short (or absent) ST segments and paroxysmal episodes of atrial or ventricular fibrillation may facilitate the correct diagnosis of SQTS.
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nord_1114_6
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Therapies of Short QT Syndrome
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TreatmentThere are no standardized protocols for the treatment of SQTS patients. The rarity of the disease and its recent description has prevented the design of clinical trials on appropriate groups of patients. A team of specialists including cardiologists and other healthcare professionals together should determine the plan of treatment of patients and their families.In general, clinical manifestations, family history and a positive electrophysiological study or genetic test may support the implantation of an implantable cardioverter defibrillator (ICD), since SQTS patients have a high risk of SCD. By delivering an electric shock, the device can be lifesaving by restoring the normal heartbeat if an abnormal rhythm is detected. Moreover, the newer-generation ICDs, also include the ability to act as pacemakers. An ICD is the first-line and most effective therapy in patients with severe arrhythmias, but its implantation is controversial in asymptomatic SQTS patients. In addition, the use of an ICD is not recommended in small children and there are adult patients in whom it is also not a therapeutic option. In symptomatic patients in whom an ICD is not implanted, pharmacological treatment is mandatory. Recommended drugs are anti-arrhythmics like ibutilide, flecainide, sotalol, amiodarone and propafenone, and beta-adrenergic blockers (beta-blockers) like metoprolol and carvedilol. Beta-blockers reduce adrenergic input to the heart, a mechanism that helps control the heartbeat and prevent symptoms. However, due to the lack of conclusive clinical studies, the treatment is specific to each individual patient.Nowadays, quinidine and hydroxyquinidine are tested as pharmacological treatments of SQTS patients because they prolong the QTc interval duration, reducing the incidence of life-threatening arrhythmias. Nevertheless, in some countries, quinidine has been removed from the market because of important side-effects.
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Therapies of Short QT Syndrome. TreatmentThere are no standardized protocols for the treatment of SQTS patients. The rarity of the disease and its recent description has prevented the design of clinical trials on appropriate groups of patients. A team of specialists including cardiologists and other healthcare professionals together should determine the plan of treatment of patients and their families.In general, clinical manifestations, family history and a positive electrophysiological study or genetic test may support the implantation of an implantable cardioverter defibrillator (ICD), since SQTS patients have a high risk of SCD. By delivering an electric shock, the device can be lifesaving by restoring the normal heartbeat if an abnormal rhythm is detected. Moreover, the newer-generation ICDs, also include the ability to act as pacemakers. An ICD is the first-line and most effective therapy in patients with severe arrhythmias, but its implantation is controversial in asymptomatic SQTS patients. In addition, the use of an ICD is not recommended in small children and there are adult patients in whom it is also not a therapeutic option. In symptomatic patients in whom an ICD is not implanted, pharmacological treatment is mandatory. Recommended drugs are anti-arrhythmics like ibutilide, flecainide, sotalol, amiodarone and propafenone, and beta-adrenergic blockers (beta-blockers) like metoprolol and carvedilol. Beta-blockers reduce adrenergic input to the heart, a mechanism that helps control the heartbeat and prevent symptoms. However, due to the lack of conclusive clinical studies, the treatment is specific to each individual patient.Nowadays, quinidine and hydroxyquinidine are tested as pharmacological treatments of SQTS patients because they prolong the QTc interval duration, reducing the incidence of life-threatening arrhythmias. Nevertheless, in some countries, quinidine has been removed from the market because of important side-effects.
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nord_1115_0
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Overview of SHORT Syndrome
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SHORT syndrome is a rare condition described by RJ Gorlin et al in 1975 based on the striking physical features of two infants born to unaffected parents. Over time, additional individuals have been described and the clinical definition of SHORT syndrome has been expanded. Each letter of SHORT syndrome represents one of the common findings in affected persons:(S) = short stature(H) = hyperextensibility of joints and/or hernia (inguinal)(O) = ocular depression (deep-set eyes)(R) = Rieger anomaly (defective development of the eye that often leads to glaucoma)(T) = teething delayNot all of these five features are required for diagnosis of SHORT syndrome.
Other characteristics common in SHORT syndrome are a triangular face, small chin with a dimple, a loss of fat under the skin (lipodystrophy), hearing loss, intrauterine growth restriction (IUGR) (poor fetal growth and low weight) and delayed speech.
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Overview of SHORT Syndrome. SHORT syndrome is a rare condition described by RJ Gorlin et al in 1975 based on the striking physical features of two infants born to unaffected parents. Over time, additional individuals have been described and the clinical definition of SHORT syndrome has been expanded. Each letter of SHORT syndrome represents one of the common findings in affected persons:(S) = short stature(H) = hyperextensibility of joints and/or hernia (inguinal)(O) = ocular depression (deep-set eyes)(R) = Rieger anomaly (defective development of the eye that often leads to glaucoma)(T) = teething delayNot all of these five features are required for diagnosis of SHORT syndrome.
Other characteristics common in SHORT syndrome are a triangular face, small chin with a dimple, a loss of fat under the skin (lipodystrophy), hearing loss, intrauterine growth restriction (IUGR) (poor fetal growth and low weight) and delayed speech.
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nord_1115_1
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Symptoms of SHORT Syndrome
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SHORT syndrome is a disorder that affects multiple organ systems. This condition was initially characterized by short stature, joints that stretch more than usual (hyperextensibility), a particular type of hernia in which the intestine protrudes through a weak spot in the abdominal muscles (inguinal hernia), deep set eyes (ocular depression), defective development of the anterior chamber of the eye that can lead to glaucoma (Rieger anomaly) and delayed eruption of teeth.In addition to the classic features, other characteristics that are common in SHORT syndrome include a triangular face, small chin with a dimple, abnormal position of the ears and hearing loss. Loss of fat under the skin (lipodystrophy) is also common, causing difficulty gaining weight and a translucent appearance to the skin. This typically presents first in the face followed by the chest and upper extremities in the first few years of development. Often, the lower extremities are spared from lipodystrophy, but overall body appearance is thin with low body mass index (BMI). Some affected individuals have speech delay and other developmental delays but intelligence is normal. In addition to teething delay, development of further dental issues is likely. Insulin resistance is common in mid-childhood to adolescence, often progressing into diabetes mellitus by early adulthood. Babies with SHORT syndrome are usually born at or slightly before term, but often have low birth weight, small head circumference and shortened length. Individuals with SHORT syndrome are thought to have a normal life-expectancy.
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Symptoms of SHORT Syndrome. SHORT syndrome is a disorder that affects multiple organ systems. This condition was initially characterized by short stature, joints that stretch more than usual (hyperextensibility), a particular type of hernia in which the intestine protrudes through a weak spot in the abdominal muscles (inguinal hernia), deep set eyes (ocular depression), defective development of the anterior chamber of the eye that can lead to glaucoma (Rieger anomaly) and delayed eruption of teeth.In addition to the classic features, other characteristics that are common in SHORT syndrome include a triangular face, small chin with a dimple, abnormal position of the ears and hearing loss. Loss of fat under the skin (lipodystrophy) is also common, causing difficulty gaining weight and a translucent appearance to the skin. This typically presents first in the face followed by the chest and upper extremities in the first few years of development. Often, the lower extremities are spared from lipodystrophy, but overall body appearance is thin with low body mass index (BMI). Some affected individuals have speech delay and other developmental delays but intelligence is normal. In addition to teething delay, development of further dental issues is likely. Insulin resistance is common in mid-childhood to adolescence, often progressing into diabetes mellitus by early adulthood. Babies with SHORT syndrome are usually born at or slightly before term, but often have low birth weight, small head circumference and shortened length. Individuals with SHORT syndrome are thought to have a normal life-expectancy.
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SHORT Syndrome
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nord_1115_2
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Causes of SHORT Syndrome
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SHORT syndrome is caused by changes (pathogenic variations) in the PIK3R1 gene. This gene is responsible for proper function of the enzyme PI3K. Enzymes are proteins that are required for cellular reactions. Specifically, PI3K is involved in cell growth and division, transport of materials within cells, movement of cells and regulation of the hormone insulin.SHORT syndrome is inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The pathogenic variant can be inherited from either parent if affected or can be the result of a new (de novo) variant in the affected individual. The risk of passing the pathogenic variant 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 SHORT Syndrome. SHORT syndrome is caused by changes (pathogenic variations) in the PIK3R1 gene. This gene is responsible for proper function of the enzyme PI3K. Enzymes are proteins that are required for cellular reactions. Specifically, PI3K is involved in cell growth and division, transport of materials within cells, movement of cells and regulation of the hormone insulin.SHORT syndrome is inherited in an autosomal dominant manner. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The pathogenic variant can be inherited from either parent if affected or can be the result of a new (de novo) variant in the affected individual. The risk of passing the pathogenic variant 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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SHORT Syndrome
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nord_1115_3
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Affects of SHORT Syndrome
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SHORT syndrome is a very rare disorder with fewer than 50 reported cases in the literature to date. SHORT syndrome is not known to be more prevalent in a certain ethnic group or geographic location.
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Affects of SHORT Syndrome. SHORT syndrome is a very rare disorder with fewer than 50 reported cases in the literature to date. SHORT syndrome is not known to be more prevalent in a certain ethnic group or geographic location.
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SHORT Syndrome
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nord_1115_4
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Related disorders of SHORT Syndrome
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Symptoms of the following disorders can be similar to those of SHORT syndrome. Comparisons may be useful for a differential diagnosis:Rieger syndrome: a rare disorder inherited in an autosomal dominant pattern. The main characteristics are facial, dental and eye abnormalities. Facial characteristics include a small jaw, broad nasal bridge and/or a protruding lower lip. Although Rieger anomaly is a classic feature of SHORT syndrome, an individual may have Rieger syndrome alone without the other clinical features of SHORT syndrome. (For more information on this disorder choose “Rieger” as your search term in the Rare Disease Database.)Russell-Silver syndrome: a rare disorder characterized by intrauterine growth restriction (IUGR) and growth deficiency after birth. This can also be characterized by short stature, a small triangular-shaped face, short arms and light brown spots on the skin (cafe-au-lait spots). The corners of the mouth turn downward and short incurved fifth fingers are apparent. Intelligence is often normal although in some children intellectual disability may occur. (For more information on this disorder, choose “Russell-Silver” as your search term in the Rare Disease Database.)Alagille syndrome: a rare genetic disorder that can affect multiple organ systems of the body including the liver, heart, skeleton, eyes and kidneys. Common symptoms, which often develop during the first three months of life include blockage of the flow of bile from the liver (cholestasis), yellowing of the skin and mucous membranes (jaundice), poor weight gain and growth, severe itching and pale, loose stools. The eye and dental features of Alagille syndrome are similar to those of SHORT syndrome, but the liver abnormalities of Alagille syndrome are not seen in SHORT syndrome. (For more information on this disorder, choose “Alagille” as your search term in the Rare Disease Database.)Congenital generalized lipodystrophy (Berardinelli-Seip syndrome): a rare genetic disorder characterized by the near total loss of body fat (adipose tissue) and extreme muscularity that is often present at birth or soon thereafter. Insulin resistance and diabetes mellitus are also common later in life. The degree of lipodystrophy is much more severe in congenital generalized lipodystrophy compared to SHORT syndrome. (For more information on this disorder, choose “congenital generalized lipodystrophy” as your search term in the Rare Disease Database.)Hutchinson-Gilford progeria syndrome: a rare, fatal, genetic condition of childhood with striking features resembling premature aging. Individuals develop a distinctive facial appearance characterized by a disproportionately small face in comparison to the head; an underdeveloped jaw (micrognathia); malformation and crowding of the teeth; abnormally prominent eyes; a small nose; prominent eyes and a subtle blueness around the mouth. These features are similar to those of SHORT syndrome, but individuals with SHORT syndrome do not have the features associated with accelerated aging. (For more information on this disorder, choose “Hutchinson-Gilford progeria” as your search term in the Rare Disease Database.)
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Related disorders of SHORT Syndrome. Symptoms of the following disorders can be similar to those of SHORT syndrome. Comparisons may be useful for a differential diagnosis:Rieger syndrome: a rare disorder inherited in an autosomal dominant pattern. The main characteristics are facial, dental and eye abnormalities. Facial characteristics include a small jaw, broad nasal bridge and/or a protruding lower lip. Although Rieger anomaly is a classic feature of SHORT syndrome, an individual may have Rieger syndrome alone without the other clinical features of SHORT syndrome. (For more information on this disorder choose “Rieger” as your search term in the Rare Disease Database.)Russell-Silver syndrome: a rare disorder characterized by intrauterine growth restriction (IUGR) and growth deficiency after birth. This can also be characterized by short stature, a small triangular-shaped face, short arms and light brown spots on the skin (cafe-au-lait spots). The corners of the mouth turn downward and short incurved fifth fingers are apparent. Intelligence is often normal although in some children intellectual disability may occur. (For more information on this disorder, choose “Russell-Silver” as your search term in the Rare Disease Database.)Alagille syndrome: a rare genetic disorder that can affect multiple organ systems of the body including the liver, heart, skeleton, eyes and kidneys. Common symptoms, which often develop during the first three months of life include blockage of the flow of bile from the liver (cholestasis), yellowing of the skin and mucous membranes (jaundice), poor weight gain and growth, severe itching and pale, loose stools. The eye and dental features of Alagille syndrome are similar to those of SHORT syndrome, but the liver abnormalities of Alagille syndrome are not seen in SHORT syndrome. (For more information on this disorder, choose “Alagille” as your search term in the Rare Disease Database.)Congenital generalized lipodystrophy (Berardinelli-Seip syndrome): a rare genetic disorder characterized by the near total loss of body fat (adipose tissue) and extreme muscularity that is often present at birth or soon thereafter. Insulin resistance and diabetes mellitus are also common later in life. The degree of lipodystrophy is much more severe in congenital generalized lipodystrophy compared to SHORT syndrome. (For more information on this disorder, choose “congenital generalized lipodystrophy” as your search term in the Rare Disease Database.)Hutchinson-Gilford progeria syndrome: a rare, fatal, genetic condition of childhood with striking features resembling premature aging. Individuals develop a distinctive facial appearance characterized by a disproportionately small face in comparison to the head; an underdeveloped jaw (micrognathia); malformation and crowding of the teeth; abnormally prominent eyes; a small nose; prominent eyes and a subtle blueness around the mouth. These features are similar to those of SHORT syndrome, but individuals with SHORT syndrome do not have the features associated with accelerated aging. (For more information on this disorder, choose “Hutchinson-Gilford progeria” as your search term in the Rare Disease Database.)
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SHORT Syndrome
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nord_1115_5
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Diagnosis of SHORT Syndrome
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The diagnosis of SHORT syndrome is based on physical findings, with facial features being particularly important, and molecular genetic testing for pathogenic variants in the PIK3R1 gene.
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Diagnosis of SHORT Syndrome. The diagnosis of SHORT syndrome is based on physical findings, with facial features being particularly important, and molecular genetic testing for pathogenic variants in the PIK3R1 gene.
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SHORT Syndrome
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nord_1115_6
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Therapies of SHORT Syndrome
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No specific treatment exists for SHORT syndrome. Treatment is symptomatic and supportive based on the features present in each patient. Rieger anomaly/glaucoma, dental anomalies, insulin resistance/diabetes mellitus and hearing loss can often be treated by appropriate medical specialists. Given the increased risk for insulin resistance, it is generally advisable to avoid growth hormone treatments.Genetic counseling is recommended for patients and their families.
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Therapies of SHORT Syndrome. No specific treatment exists for SHORT syndrome. Treatment is symptomatic and supportive based on the features present in each patient. Rieger anomaly/glaucoma, dental anomalies, insulin resistance/diabetes mellitus and hearing loss can often be treated by appropriate medical specialists. Given the increased risk for insulin resistance, it is generally advisable to avoid growth hormone treatments.Genetic counseling is recommended for patients and their families.
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SHORT Syndrome
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nord_1116_0
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Overview of Shprintzen Goldberg Syndrome
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SummaryShprintzen Goldberg syndrome (SGS) is an extremely rare connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular deformities. Patients with SGS generally present with premature fusion of cranial bones in infancy (craniosynostosis), distinctive facial features, elongated fingers and limbs, umbilical and abdominal hernias, developmental delays, intellectual disability, and cardiac problems. In addition, individuals with SGS may have brain anomalies including fluid build-up in the brain (hydrocephalus); dilation of the lateral ventricles; and Chiari 1 malformation, a condition caused by the skull at the nape pushing brain tissue into the spinal column. Cardiovascular anomalies found in patients with SGS may include regurgitation or prolapse of the valves and aortic root enlargement and aneurysm. SGS is inherited as an autosomal dominant trait and thought to be caused by changes (mutations) of the SKI gene, important in cell growth and development. Currently, there are fewer than 50 patients described in the medical literature.IntroductionSGS is often misdiagnosed as Marfan syndrome or Loeys-Dietz syndrome due to the similar presentation of facial, skeletal and cardiovascular features. However, intellectual disability is uniquely and strongly associated with SGS, and cardiovascular abnormalities tend to be less common and less severe than seen in patients with Marfan syndrome or Loeys-Dietz syndrome.
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Overview of Shprintzen Goldberg Syndrome. SummaryShprintzen Goldberg syndrome (SGS) is an extremely rare connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular deformities. Patients with SGS generally present with premature fusion of cranial bones in infancy (craniosynostosis), distinctive facial features, elongated fingers and limbs, umbilical and abdominal hernias, developmental delays, intellectual disability, and cardiac problems. In addition, individuals with SGS may have brain anomalies including fluid build-up in the brain (hydrocephalus); dilation of the lateral ventricles; and Chiari 1 malformation, a condition caused by the skull at the nape pushing brain tissue into the spinal column. Cardiovascular anomalies found in patients with SGS may include regurgitation or prolapse of the valves and aortic root enlargement and aneurysm. SGS is inherited as an autosomal dominant trait and thought to be caused by changes (mutations) of the SKI gene, important in cell growth and development. Currently, there are fewer than 50 patients described in the medical literature.IntroductionSGS is often misdiagnosed as Marfan syndrome or Loeys-Dietz syndrome due to the similar presentation of facial, skeletal and cardiovascular features. However, intellectual disability is uniquely and strongly associated with SGS, and cardiovascular abnormalities tend to be less common and less severe than seen in patients with Marfan syndrome or Loeys-Dietz syndrome.
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nord_1116_1
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Symptoms of Shprintzen Goldberg Syndrome
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Most SGS newborns are born full term and have normal weight, height, and head circumference parameters. Both males and females may be affected. Craniosynostosis is a common characteristic of SGS. This early fusion prevents the skull from growing normally. Individuals with SGS tend to have mild to moderate intellectual and cognitive disabilities that can be seen in the absence of craniosynostosis.SGS patients present with distinctive facial features, including a long, narrow head; widely spaced eyes (hypertelorism); protruding eyes (exophthalmos); outside corners of the eyes that point downward (downslanting palpebral fissures); a high, narrow palate; a small lower jaw (micrognathia); and low-set ears that are rotated backward. While highly arched palate can be seen in Marfan syndrome and Loeys-Dietz syndrome, patients with SGS often show prominence at the base of the palate, leading to a characteristic “Byzantine arch” appearance.The physical characteristics of SGS are often said to mimic the “marfanoid habitus” (Marfan features) because their bodies resemble those of individuals with Marfan syndrome. Individuals with SGS have unusually long, slender fingers (arachnodactyly) and limbs, sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and an abnormal side-to-side curvature of the spine (scoliosis). Other skeletal abnormalities include one or more fingers that are permanently bent (camptodactyly), and an unusually large range of joint movement (hypermobility).SGS patients may also present with cardiac anomalies such as valve regurgitation or prolapse and aortic root dilation and aneurysm. Some individuals with SGS present with respiratory distress, abdominal hernias, translucent skin that bruises easily, and hypotonia. In addition, SGS may contribute to gastrointestinal problems such as constipation and delayed gastric emptying (gastroparesis).Summary of symptoms identified in patients with SGS:Facial Features• A long, narrow head (dolichocephaly)
• High prominent forehead
• Widely spaced eyes (hypertelorism)
• Protruding or bulging eyes (exophthalmos, ocular proptosis)
• Wandering eye (strabismus)
• Outside corners of the eyes point downward (down-slanting palpebral fissures)
• Increased angle of the eyelids (telecanthus)
• A high, narrow palate (roof of the mouth
• Wide or split uvula (exceedingly rare when compared to Loeys-Dietz syndrome)
• Under-developed jaw bones (maxillary hypoplasia)
• Small lower jaw (micrognathia)
• Low-set ears that are rotated backward
• Increased angle of the eyelids (telecanthus)
• Smaller than normal tongue (microglossia/retroglossia)Bone/Skeletal abnormalities• Premature fusion of one or more sutures of skull (craniosynostosis)
• Abnormalities of the cervical spine (C1 C2)
• Curvature of the spine (scoliosis)
• Slippage of the vertebrae (spondylolisthesis)
• Square-shaped vertebral bodies
• Limbs are unusually long (dolichostenomelia)
• Fingers and toes are unusually long and narrow (arachnodactyly)
• Abnormal bending of joint of finger (camptodactyly)
• Flat feet (pes planus)
• Thin ribs
• 13 pairs of ribs
• Chest wall is “sunken in” or “sticking out” due to abnormal development of breast bone and ribs (pectus excavatum or carinatum)
• Hypermobility of joints
• Malposition of foot (clubfoot)
• Bone loss (osteopenia)Heart/blood vessel issues noted with SGS• Mitral valve prolapse
• Mitral and aortic valve regurgitation
• Aortic root enlargement
• Aortic Regurgitation
• Aneurysms in arteries besides the aorta (rare)Possible brain abnormalities• Brain anomalies, including water on the brain (hydrocephalus)
• Enlargement (dilatation) of the lateral ventricles
• Brain tissue protrudes into the spinal canal (Chiari 1 malformation)
• Widening of the Dural sac surrounding the spinal cord (dural ectasia)Other CharacteristicsNeurologic
• Delayed motor and cognitive milestones
• Mild-to-moderate intellectual disabilityGastrointestinal
• Constipation
• GastroparesisOther
• Umbilical and abdominal hernias
• Nearsighted vision (myopia)
• Loss of subcutaneous fat
• Loss of respiratory function at puberty (due to skeletal abnormalities)
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Symptoms of Shprintzen Goldberg Syndrome. Most SGS newborns are born full term and have normal weight, height, and head circumference parameters. Both males and females may be affected. Craniosynostosis is a common characteristic of SGS. This early fusion prevents the skull from growing normally. Individuals with SGS tend to have mild to moderate intellectual and cognitive disabilities that can be seen in the absence of craniosynostosis.SGS patients present with distinctive facial features, including a long, narrow head; widely spaced eyes (hypertelorism); protruding eyes (exophthalmos); outside corners of the eyes that point downward (downslanting palpebral fissures); a high, narrow palate; a small lower jaw (micrognathia); and low-set ears that are rotated backward. While highly arched palate can be seen in Marfan syndrome and Loeys-Dietz syndrome, patients with SGS often show prominence at the base of the palate, leading to a characteristic “Byzantine arch” appearance.The physical characteristics of SGS are often said to mimic the “marfanoid habitus” (Marfan features) because their bodies resemble those of individuals with Marfan syndrome. Individuals with SGS have unusually long, slender fingers (arachnodactyly) and limbs, sunken chest (pectus excavatum) or protruding chest (pectus carinatum), and an abnormal side-to-side curvature of the spine (scoliosis). Other skeletal abnormalities include one or more fingers that are permanently bent (camptodactyly), and an unusually large range of joint movement (hypermobility).SGS patients may also present with cardiac anomalies such as valve regurgitation or prolapse and aortic root dilation and aneurysm. Some individuals with SGS present with respiratory distress, abdominal hernias, translucent skin that bruises easily, and hypotonia. In addition, SGS may contribute to gastrointestinal problems such as constipation and delayed gastric emptying (gastroparesis).Summary of symptoms identified in patients with SGS:Facial Features• A long, narrow head (dolichocephaly)
• High prominent forehead
• Widely spaced eyes (hypertelorism)
• Protruding or bulging eyes (exophthalmos, ocular proptosis)
• Wandering eye (strabismus)
• Outside corners of the eyes point downward (down-slanting palpebral fissures)
• Increased angle of the eyelids (telecanthus)
• A high, narrow palate (roof of the mouth
• Wide or split uvula (exceedingly rare when compared to Loeys-Dietz syndrome)
• Under-developed jaw bones (maxillary hypoplasia)
• Small lower jaw (micrognathia)
• Low-set ears that are rotated backward
• Increased angle of the eyelids (telecanthus)
• Smaller than normal tongue (microglossia/retroglossia)Bone/Skeletal abnormalities• Premature fusion of one or more sutures of skull (craniosynostosis)
• Abnormalities of the cervical spine (C1 C2)
• Curvature of the spine (scoliosis)
• Slippage of the vertebrae (spondylolisthesis)
• Square-shaped vertebral bodies
• Limbs are unusually long (dolichostenomelia)
• Fingers and toes are unusually long and narrow (arachnodactyly)
• Abnormal bending of joint of finger (camptodactyly)
• Flat feet (pes planus)
• Thin ribs
• 13 pairs of ribs
• Chest wall is “sunken in” or “sticking out” due to abnormal development of breast bone and ribs (pectus excavatum or carinatum)
• Hypermobility of joints
• Malposition of foot (clubfoot)
• Bone loss (osteopenia)Heart/blood vessel issues noted with SGS• Mitral valve prolapse
• Mitral and aortic valve regurgitation
• Aortic root enlargement
• Aortic Regurgitation
• Aneurysms in arteries besides the aorta (rare)Possible brain abnormalities• Brain anomalies, including water on the brain (hydrocephalus)
• Enlargement (dilatation) of the lateral ventricles
• Brain tissue protrudes into the spinal canal (Chiari 1 malformation)
• Widening of the Dural sac surrounding the spinal cord (dural ectasia)Other CharacteristicsNeurologic
• Delayed motor and cognitive milestones
• Mild-to-moderate intellectual disabilityGastrointestinal
• Constipation
• GastroparesisOther
• Umbilical and abdominal hernias
• Nearsighted vision (myopia)
• Loss of subcutaneous fat
• Loss of respiratory function at puberty (due to skeletal abnormalities)
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Shprintzen Goldberg Syndrome
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Causes of Shprintzen Goldberg Syndrome
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SGS is one of many diseases that arise from genetic mutations that affect the TGF-β signaling pathway. The TGF-β signaling pathway regulates many aspects of early development, and thus SGS patients and people with related diseases display a variety of physical malformations.SGS is caused by mutations in the SKI gene, which codes for a protein known to repress TGF-β signaling. Mutations in the SKI gene result in production of altered SKI proteins that allow TGF-β signaling to continue uncontrolled. This leads to abnormal development of many body systems.Rare individuals thought to have SGS do not have a SKI gene mutation, suggesting that other genes may be associated with this condition that have not yet been identified.SGS is an autosomal dominant genetic condition. Autosomal dominant disorders occur when only a single copy of an altered gene is necessary to cause a particular disease. The altered gene can be inherited from either parent or can be the result of a new mutation in the affected individual. The risk of passing the altered 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. In most patients, the SKI gene mutations causing SGS appear to be de novo mutations.
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Causes of Shprintzen Goldberg Syndrome. SGS is one of many diseases that arise from genetic mutations that affect the TGF-β signaling pathway. The TGF-β signaling pathway regulates many aspects of early development, and thus SGS patients and people with related diseases display a variety of physical malformations.SGS is caused by mutations in the SKI gene, which codes for a protein known to repress TGF-β signaling. Mutations in the SKI gene result in production of altered SKI proteins that allow TGF-β signaling to continue uncontrolled. This leads to abnormal development of many body systems.Rare individuals thought to have SGS do not have a SKI gene mutation, suggesting that other genes may be associated with this condition that have not yet been identified.SGS is an autosomal dominant genetic condition. Autosomal dominant disorders occur when only a single copy of an altered gene is necessary to cause a particular disease. The altered gene can be inherited from either parent or can be the result of a new mutation in the affected individual. The risk of passing the altered 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. In most patients, the SKI gene mutations causing SGS appear to be de novo mutations.
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Shprintzen Goldberg Syndrome
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Affects of Shprintzen Goldberg Syndrome
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SGS affects males and females in equal numbers and occurs worldwide with no ethnic predisposition. There are currently approximately 40 known patients in the general population. Because of the similar symptoms, SGS is often misdiagnosed as Loeys-Dietz or Marfan syndrome. The disorder is probably underdiagnosed, making it difficult to determine its true frequency.
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Affects of Shprintzen Goldberg Syndrome. SGS affects males and females in equal numbers and occurs worldwide with no ethnic predisposition. There are currently approximately 40 known patients in the general population. Because of the similar symptoms, SGS is often misdiagnosed as Loeys-Dietz or Marfan syndrome. The disorder is probably underdiagnosed, making it difficult to determine its true frequency.
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Shprintzen Goldberg Syndrome
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Related disorders of Shprintzen Goldberg Syndrome
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Loeys- Dietz syndrome (LDS)
There are many similarities that make it difficult to differentiate SGS from Loeys Dietz or Marfan syndrome. LDS is also an autosomal dominant connective tissue disorder that can affect the skin, the cardiovascular, musculoskeletal, and gastrointestinal systems. Dr. Bart Loeys and Dr. Hal Dietz identified this disorder similar to SGS at the Johns Hopkins University School of Medicine in 2005. Arterial tortuosity (arteries that twist and wind) and aneurysms in arteries other than the aorta are cardinal signs of LDS. Many, but not all, patients with LDS show the craniofacial, skeletal and cutaneous features that overlap with SGS or MFS. Patients with LDS have a tendency to present with velvety skin, easy bruising, atrophic or wide scarring and pregnancy complications such as uterine rupture. Symptoms of intellectual disability and selected distinctive radiographic findings found in SGS are rarely seen in LDS or Marfan. Patients with LDS typically show aortic root aneurysm and more commonly show aneurysms elsewhere in the arterial tree than in SDS or MFS. These aneurysms can tear or rupture at smaller sizes and younger ages, when compared to MFS. LDS can be caused by mutations in at least 5 genes. Molecular genetic testing for mutations in the TGFBR1, TGFBR2, SMAD3, TGFB2 and TGFB3 genes is clinically available if there is high suspicion of the diagnosis of LDS.Marfan syndrome (MFS)
MFS is an additional autosomal dominant connective tissue disorder that mainly affects the heart and blood vessels (cardiovascular), skeletal, and eye (ocular) systems Major symptoms include overgrowth of the long bones of the arms and legs, abnormal side-to-side curvature of the spine (scoliosis), and indentation or protrusion of the chest wall (pectus deformity). The most common eye disorder found in MFS is nearsightedness (myopia) and dislocation of the lenses of the eyes (ectopia lentis) occurs in about 60 % of individuals with MFS. Eye lens dislocation distinguishes MFS from either SGS or LDS. Widening (aneurysm) and tear (dissection) of the main artery that carries blood away from the heart (aorta), floppiness of the mitral valve (mitral valve prolapse) and backward flow of blood through the aortic and mitral valves (aortic and mitral regurgitation) are symptoms prevalent in people with Marfan syndrome. A mutation in the FBN1 gene is found in about 95% of people with MFS. (For more information on this disorder, choose “Marfan” as your search term on the Rare Disease Database.)Congenital contractural arachnodactyly (CCA) is a MFS-like autosomal dominant connective tissue disorder. Like MFS, individuals can have long, slender fingers and toes and arm spans that exceed their height. Most individuals have permanent fixation of certain joints in a flexed position (contractures) that is present at birth (congenital) and is progressive. The joints of the fingers, elbows, knees, and hips are most often affected. The contractures generally improve with age. A “crumpled” appearance to the ears, side-to-side curvature of the spine (kyphoscoliosis); feet that are abnormally positioned (clubfoot); outward displacement of the fingers (ulnar deviation of the fingers); and an abnormally short neck are all commonly found in people with CCA. Rarely, affected individuals may have a slight deformity of the valve on the left side of the heart (mitral valve prolapse). FBN2 is the only gene that has been found to be associated with CCA. A severe lethal form has been found in infants and is characterized by cardiovascular and gastrointestinal anomalies as well as the skeletal features. This is exceedingly rare. (For more information on this disorder, choose “congenital contractural arachnodactyly” as your search term on the Rare Disease Database.)Frontometaphyseal dysplasia (FMD) and Melnick-Needles syndrome (MNS)
FMD and MNS share similar skeletal features that are found in SGS, including abnormalities in the vertebrae, but generally will not show the presence of intellectual disability and craniosynostosis that is found in SGS.
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Related disorders of Shprintzen Goldberg Syndrome. Loeys- Dietz syndrome (LDS)
There are many similarities that make it difficult to differentiate SGS from Loeys Dietz or Marfan syndrome. LDS is also an autosomal dominant connective tissue disorder that can affect the skin, the cardiovascular, musculoskeletal, and gastrointestinal systems. Dr. Bart Loeys and Dr. Hal Dietz identified this disorder similar to SGS at the Johns Hopkins University School of Medicine in 2005. Arterial tortuosity (arteries that twist and wind) and aneurysms in arteries other than the aorta are cardinal signs of LDS. Many, but not all, patients with LDS show the craniofacial, skeletal and cutaneous features that overlap with SGS or MFS. Patients with LDS have a tendency to present with velvety skin, easy bruising, atrophic or wide scarring and pregnancy complications such as uterine rupture. Symptoms of intellectual disability and selected distinctive radiographic findings found in SGS are rarely seen in LDS or Marfan. Patients with LDS typically show aortic root aneurysm and more commonly show aneurysms elsewhere in the arterial tree than in SDS or MFS. These aneurysms can tear or rupture at smaller sizes and younger ages, when compared to MFS. LDS can be caused by mutations in at least 5 genes. Molecular genetic testing for mutations in the TGFBR1, TGFBR2, SMAD3, TGFB2 and TGFB3 genes is clinically available if there is high suspicion of the diagnosis of LDS.Marfan syndrome (MFS)
MFS is an additional autosomal dominant connective tissue disorder that mainly affects the heart and blood vessels (cardiovascular), skeletal, and eye (ocular) systems Major symptoms include overgrowth of the long bones of the arms and legs, abnormal side-to-side curvature of the spine (scoliosis), and indentation or protrusion of the chest wall (pectus deformity). The most common eye disorder found in MFS is nearsightedness (myopia) and dislocation of the lenses of the eyes (ectopia lentis) occurs in about 60 % of individuals with MFS. Eye lens dislocation distinguishes MFS from either SGS or LDS. Widening (aneurysm) and tear (dissection) of the main artery that carries blood away from the heart (aorta), floppiness of the mitral valve (mitral valve prolapse) and backward flow of blood through the aortic and mitral valves (aortic and mitral regurgitation) are symptoms prevalent in people with Marfan syndrome. A mutation in the FBN1 gene is found in about 95% of people with MFS. (For more information on this disorder, choose “Marfan” as your search term on the Rare Disease Database.)Congenital contractural arachnodactyly (CCA) is a MFS-like autosomal dominant connective tissue disorder. Like MFS, individuals can have long, slender fingers and toes and arm spans that exceed their height. Most individuals have permanent fixation of certain joints in a flexed position (contractures) that is present at birth (congenital) and is progressive. The joints of the fingers, elbows, knees, and hips are most often affected. The contractures generally improve with age. A “crumpled” appearance to the ears, side-to-side curvature of the spine (kyphoscoliosis); feet that are abnormally positioned (clubfoot); outward displacement of the fingers (ulnar deviation of the fingers); and an abnormally short neck are all commonly found in people with CCA. Rarely, affected individuals may have a slight deformity of the valve on the left side of the heart (mitral valve prolapse). FBN2 is the only gene that has been found to be associated with CCA. A severe lethal form has been found in infants and is characterized by cardiovascular and gastrointestinal anomalies as well as the skeletal features. This is exceedingly rare. (For more information on this disorder, choose “congenital contractural arachnodactyly” as your search term on the Rare Disease Database.)Frontometaphyseal dysplasia (FMD) and Melnick-Needles syndrome (MNS)
FMD and MNS share similar skeletal features that are found in SGS, including abnormalities in the vertebrae, but generally will not show the presence of intellectual disability and craniosynostosis that is found in SGS.
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Shprintzen Goldberg Syndrome
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Diagnosis of Shprintzen Goldberg Syndrome
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Shprintzen Goldberg syndrome is generally diagnosed after a thorough physical examination and the presence of certain craniofacial, skeletal, cardiovascular, neurologic features and brain anomalies. There is currently no test for SGS other than identification of mutations in the SKI gene. To date, this is the only identified gene associated with SGS.
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Diagnosis of Shprintzen Goldberg Syndrome. Shprintzen Goldberg syndrome is generally diagnosed after a thorough physical examination and the presence of certain craniofacial, skeletal, cardiovascular, neurologic features and brain anomalies. There is currently no test for SGS other than identification of mutations in the SKI gene. To date, this is the only identified gene associated with SGS.
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Shprintzen Goldberg Syndrome
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Therapies of Shprintzen Goldberg Syndrome
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TreatmentTreatments for SGS are currently limited to symptom management. Treatments are primarily surgical: repair of aneurysms and heart valves and correction of craniofacial, spinal, or chest malformations may be necessary and beneficial. X-ray of the neck and spine should be done annually to assess for skeletal changes and surgical fusion of the cervical vertebrae C1 and C2 may be needed. MRA (magnetic resonance angiography) or CTA (computed tomography angiography) is recommended every two years to assess from head to pelvis in patients with SGS. Bone density scan should be performed in all people diagnosed with SGS.Patients often receive occupational, physical, and speech therapy and bracing of feet and/or spine may help with ambulation. Feeding may need to come exclusively or be supplemented by a feeding tube. CPAP can be used if patient suffers from obstructive apnea. Tracheostomy or tracheostomy may be needed if airway is obstructed by abnormality in the structure of bone or tissue at the back of nasal passage (choanal atresia). An eye exam with an ophthalmologist that specializes in connective tissue disease is recommended yearly and glasses may be prescribed for myopia. Annual exams with a cardiologist are recommended and medications (beta blocker or angiotensin receptor blocker) should be considered for those patients with abnormal aortic growth. Echocardiograms should be conducted yearly to monitor aortic size and heart function.
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Therapies of Shprintzen Goldberg Syndrome. TreatmentTreatments for SGS are currently limited to symptom management. Treatments are primarily surgical: repair of aneurysms and heart valves and correction of craniofacial, spinal, or chest malformations may be necessary and beneficial. X-ray of the neck and spine should be done annually to assess for skeletal changes and surgical fusion of the cervical vertebrae C1 and C2 may be needed. MRA (magnetic resonance angiography) or CTA (computed tomography angiography) is recommended every two years to assess from head to pelvis in patients with SGS. Bone density scan should be performed in all people diagnosed with SGS.Patients often receive occupational, physical, and speech therapy and bracing of feet and/or spine may help with ambulation. Feeding may need to come exclusively or be supplemented by a feeding tube. CPAP can be used if patient suffers from obstructive apnea. Tracheostomy or tracheostomy may be needed if airway is obstructed by abnormality in the structure of bone or tissue at the back of nasal passage (choanal atresia). An eye exam with an ophthalmologist that specializes in connective tissue disease is recommended yearly and glasses may be prescribed for myopia. Annual exams with a cardiologist are recommended and medications (beta blocker or angiotensin receptor blocker) should be considered for those patients with abnormal aortic growth. Echocardiograms should be conducted yearly to monitor aortic size and heart function.
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Shprintzen Goldberg Syndrome
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Overview of Shwachman Diamond Syndrome
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Shwachman syndrome is a rare genetic disorder with multiple and varied manifestations. The disorder is typically characterized by signs of insufficient absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency) and improper functioning of the bone marrow (bone marrow dysfunction), resulting in low levels of circulating blood cells (hematologic abnormalities). Additional characteristic findings may include short stature; abnormal bone development affecting the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); and/or liver abnormalities.Due to abnormal skeletal changes, individuals with Shwachman syndrome may have abnormal thickening of the ribs and their supporting connective tissue (costochondral thickening), resulting in unusually short, flared ribs. In addition, improper bone development (abnormal ossification) within the arms and/or legs (limbs) may cause growth delay in particular bones. Many children with Shwachman syndrome may also be smaller than expected for their ages, with below average height (short stature) and weight. Although malabsorption due to pancreatic insufficiency may itself cause problems with growth and nutrition, short stature appears to be one of the many primary manifestations of Shwachman syndrome.In addition, as a result of bone marrow dysfunction, individuals with Shwachman syndrome may have a decrease in any or all types of blood cells. Therefore, they may have low levels of certain white blood cells (neutropenia), platelets (thrombocytopenia), red blood cells (anemia), and/or all types of blood cells (pancytopenia). Neutropenia is the most common blood abnormality associated with Shwachman syndrome. Because neutrophils, a type of white blood cell, play an essential role in fighting bacterial infections, many affected individuals are prone to repeated bacterial infections (e.g., recurrent respiratory infections [pneumonia] and infections of the middle ear [otitis media]); in some cases, infections may be severe.Some affected individuals may also have abnormal enlargement of the liver (hepatomegaly), increased levels of certain liver enzymes in the blood, and/or other findings in association with the disorder. Shwachman syndrome is believed to be inherited as an autosomal recessive trait.
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Overview of Shwachman Diamond Syndrome. Shwachman syndrome is a rare genetic disorder with multiple and varied manifestations. The disorder is typically characterized by signs of insufficient absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency) and improper functioning of the bone marrow (bone marrow dysfunction), resulting in low levels of circulating blood cells (hematologic abnormalities). Additional characteristic findings may include short stature; abnormal bone development affecting the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); and/or liver abnormalities.Due to abnormal skeletal changes, individuals with Shwachman syndrome may have abnormal thickening of the ribs and their supporting connective tissue (costochondral thickening), resulting in unusually short, flared ribs. In addition, improper bone development (abnormal ossification) within the arms and/or legs (limbs) may cause growth delay in particular bones. Many children with Shwachman syndrome may also be smaller than expected for their ages, with below average height (short stature) and weight. Although malabsorption due to pancreatic insufficiency may itself cause problems with growth and nutrition, short stature appears to be one of the many primary manifestations of Shwachman syndrome.In addition, as a result of bone marrow dysfunction, individuals with Shwachman syndrome may have a decrease in any or all types of blood cells. Therefore, they may have low levels of certain white blood cells (neutropenia), platelets (thrombocytopenia), red blood cells (anemia), and/or all types of blood cells (pancytopenia). Neutropenia is the most common blood abnormality associated with Shwachman syndrome. Because neutrophils, a type of white blood cell, play an essential role in fighting bacterial infections, many affected individuals are prone to repeated bacterial infections (e.g., recurrent respiratory infections [pneumonia] and infections of the middle ear [otitis media]); in some cases, infections may be severe.Some affected individuals may also have abnormal enlargement of the liver (hepatomegaly), increased levels of certain liver enzymes in the blood, and/or other findings in association with the disorder. Shwachman syndrome is believed to be inherited as an autosomal recessive trait.
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Shwachman Diamond Syndrome
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Symptoms of Shwachman Diamond Syndrome
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Shwachman syndrome is a rare genetic disorder characterized by insufficient absorption (malabsorption) of necessary nutrients due to abnormal development of the pancreas (pancreatic insufficiency); impaired functioning of the bone marrow, resulting in a reduced number of certain blood cells; abnormal bone changes that may affect the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); short stature; and/or other physical and/or developmental abnormalities. The range and severity of symptoms may vary greatly from case to case. One of the primary functions of the pancreas is to produce digestive enzymes. Pancreatic cells called “acinar cells” produce such digestive enzymes. In Shwachman syndrome, however, affected individuals lack a sufficient number of properly functioning acinar cells, and pancreatic tissue may be replaced by abnormal accumulations of fat (pancreatic lipomatosis). As a result, there is a deficiency in the amount of digestive enzymes required to break down food (pancreatic insufficiency), which, in turn, prevents fats and other essential nutrients from being absorbed properly (malabsorption). In individuals with Shwachman syndrome, intestinal malabsorption results in large, loose, foul smelling stools that contain an excessive amount of fat (steatorrhea) and other nutrients. Affected infants may fail to gain the expected amount of weight or may lose weight (failure to thrive). In addition, pancreatic insufficiency may result in deficiencies of certain vitamins (e.g., vitamins A, D, K and/or E) and/or additional nutritional deficiencies. Children with Shwachman syndrome may have larger or smaller appetites than normal and be smaller than expected for their ages, which may be due, in part, to malabsorption of certain necessary nutrients. As children with Shwachman syndrome grow older, the ability of the pancreas to produce digestive enzymes may improve slightly, potentially leading to an improvement in the absorption of certain nutrients and relief of symptoms associated with malabsorption. For example, in almost 50 percent of cases, older children may begin to have normal stool patterns. However, even with improved absorption of nutrients and acceptable weight gain, most affected children will be smaller than average for their ages. Shwachman syndrome is also characterized by abnormalities of the soft tissue within bone, called bone marrow. Red bone marrow, which is found within the cavities of all bones at birth, contains immature cells known as stem cells that develop into the three cellular components of the blood. These include red blood cells, which carry oxygen to the cells of the body; white blood cells, which are involved in fighting off infections; and platelets, which help the blood to clot properly. In Shwachman syndrome, bone marrow dysfunction results in impaired production of blood cells. Almost all individuals with Shwachman syndrome have an abnormally decreased number of certain white blood cells (neutrophils). Called “neutropenia,” this condition may be persistent (chronic) or occur occasionally (paroxysmal). In extremely rare cases, neutropenia may occur in regular, predictable cycles (cyclic neutropenia). Neutrophils play an essential role in fighting bacterial infections by detecting, engulfing, and digesting invading bacteria (phagocytosis). In neutropenia associated with Shwachman syndrome, not only may there be an abnormally low number of neutrophils, but those that are present may have an impaired ability to detect and appropriately respond to invading bacteria (impaired chemotaxis). As a result, affected individuals with neutropenia may be prone to repeated bacterial infections including respiratory infections (e.g., pneumonia); infections of the middle ear (otitis media); and repeated bacterial infections of other areas of the body. Although most young children with Shwachman syndrome are prone to such repeated bacterial infections, such susceptibility may vary from case to case, depending upon the degree of neutropenia and other immune factors that help the body to fight off infections. Affected individuals with neutropenia may also have additional abnormalities believed to result from an increased susceptibility to infections. These may include increased tooth decay (dental caries), mouth ulcers, and/or disease of the tissues that surround and support the teeth (periodontal disease). The bone marrow dysfunction associated with Shwachman syndrome may result in abnormalities in the production of other types of blood cells. In some cases, affected individuals have a reduced number of circulating blood platelets (thrombocytopenia), which play an important role in clotting the blood. Individuals with thrombocytopenia may bruise easily and, without appropriate precautions, be prone to abnormal bleeding; however, episodes of severe bleeding are rare. In approximately half of individuals with Shwachman syndrome, there may be abnormally low levels of red blood cells (anemia). Because red blood cells contain hemoglobin, which functions to carry oxygen, low levels of red blood cells may result in an impaired ability to transport oxygen from the lungs to tissues throughout the body. Associated symptoms may include fatigue, abnormal paleness of the skin (pallor), and/or other findings. In addition, in some cases, failure of the bone marrow's cell-generating capacity leads to pancytopenia or decreased levels of all cellular components of the blood, potentially in association with myelodysplastic syndrome (MDS). MDS refers to bone marrow disorders characterized by abnormal stem cells and low levels of red blood cells, white blood cells, and platelets. MDS may precede the development of acute myeloid leukemia, a cancer in which cells that normally develop into certain white blood cells (granulocytes) become malignant and abnormally proliferate. Only approximately one-third of children with Shwachman syndrome eventually develop one of these conditions. Approximately half of individuals with Shwachman syndrome also have abnormal bone changes that may affect the rib cage and/or bones in the arms and/or legs (limbs). For example, some affected individuals may have abnormal thickening of the ribs and their supporting connective tissue (costochondral thickening), resulting in abnormally short, flared ribs. In addition, in rare cases, abnormal narrowness of the rib cage may cause difficulties with breathing during infancy; however, such symptoms may improve later in childhood. In cases where limb bone changes occur, the region where the long shaft of the bone (diaphysis) meets its growing end (epiphysis) may develop improperly (metaphyseal dysostosis). In most cases, metaphyseal dysostosis has no harmful effects. However, abnormal bone development (improper ossification) may cause growth delay in a particular bone. Such abnormalities may affect particular areas such as the thigh bone (femur) or the shin bone (tibia). For example, such changes may cause an abnormal reduction in the angle of the thigh bone or the knee, potentially resulting in shortening of the leg, stiffness, and/or limping. In rare cases, individuals with Shwachman syndrome may have additional skeletal malformations such as fingers that are abnormally bent (clinodactyly). Some affected infants may also have delays in tooth eruption, and their teeth may develop improperly (dental dysplasia). Another primary characteristic often associated with Shwachman syndrome is short stature. At birth, affected infants are usually of normal height and weight. However, shortly after birth, growth slows and, by the first year of life, most children are below average for height and weight. Most children continue to grow and gain weight at a normal rate but remain smaller than average. The severity of the abnormality varies greatly from case to case. Although malabsorption due to pancreatic insufficiency may cause secondary problems with growth and nutrition, short stature appears to be one of the many primary manifestations of Shwachman syndrome. Some affected children may also have an abnormally large liver (hepatomegaly) and/or increased levels of certain liver enzymes in the blood (serum liver enzymes). In addition, in some rare cases, those with the disorder may be affected by renal tubular acidosis, a condition in which there is insufficient removal of acid from the blood by the kidney (renal) tubules for excretion in the urine. The renal tubules are part of the filtering units of the kidneys (nephrons). Renal tubular acidosis may lead to increased acid levels in the blood, low blood potassium levels, abnormal calcium deposits within functional tissue (parenchyma) of the kidneys (nephrocalcinosis), softening of bones (osteomalacia), and/or other findings. Some individuals with Shwachman syndrome may also have additional physical abnormalities. For example, many may exhibit abnormally decreased saliva production, though such symptoms do not appear to contribute to digestive abnormalities. In addition, in early childhood, some with the disorder may have various skin abnormalities including rashes and/or skin that is scaly, dry, and/or rough (ichthyosiform lesions). In many cases, the skin abnormalities may decrease or cease during later childhood. In rare cases, individuals with Shwachman syndrome may have heart (cardiac) abnormalities. For example, some affected individuals may have abnormal enlargement of the right side of the heart (right-sided hypertrophy). In addition, per reports in the medical literature, children with Shwachman syndrome in a small population in Finland have had an abnormally increased incidence of heart muscle (myocardial) abnormalities as a secondary characteristic in association with the disorder. In such cases, the abnormal formation of scar tissue within heart muscle (myocardial fibrosis) may result in tissue damage and loss (necrosis) in certain areas of the heart (e.g., left ventricle), potentially resulting in life-threatening complications (e.g., heart failure). However, researchers have not observed such patterns of myocardial fibrosis in children with Shwachman syndrome in other geographic locations. In extremely rare cases, individuals with Shwachman syndrome may also have nervous system abnormalities. These may include an impaired ability to perform certain voluntary movements (apraxia), low muscle tone (hypotonia), and/or general weakness. In addition, in some cases, children with Shwachman syndrome may experience a delay in reaching developmental milestones (such as crawling, sitting, walking, learning to speak, etc. [delayed motor and speech development]); however, by school age, affected children usually reach their expected milestones. Most children with Shwachman syndrome have normal intelligence; however, in some cases, affected children may have a below-normal I.Q.
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Symptoms of Shwachman Diamond Syndrome. Shwachman syndrome is a rare genetic disorder characterized by insufficient absorption (malabsorption) of necessary nutrients due to abnormal development of the pancreas (pancreatic insufficiency); impaired functioning of the bone marrow, resulting in a reduced number of certain blood cells; abnormal bone changes that may affect the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis); short stature; and/or other physical and/or developmental abnormalities. The range and severity of symptoms may vary greatly from case to case. One of the primary functions of the pancreas is to produce digestive enzymes. Pancreatic cells called “acinar cells” produce such digestive enzymes. In Shwachman syndrome, however, affected individuals lack a sufficient number of properly functioning acinar cells, and pancreatic tissue may be replaced by abnormal accumulations of fat (pancreatic lipomatosis). As a result, there is a deficiency in the amount of digestive enzymes required to break down food (pancreatic insufficiency), which, in turn, prevents fats and other essential nutrients from being absorbed properly (malabsorption). In individuals with Shwachman syndrome, intestinal malabsorption results in large, loose, foul smelling stools that contain an excessive amount of fat (steatorrhea) and other nutrients. Affected infants may fail to gain the expected amount of weight or may lose weight (failure to thrive). In addition, pancreatic insufficiency may result in deficiencies of certain vitamins (e.g., vitamins A, D, K and/or E) and/or additional nutritional deficiencies. Children with Shwachman syndrome may have larger or smaller appetites than normal and be smaller than expected for their ages, which may be due, in part, to malabsorption of certain necessary nutrients. As children with Shwachman syndrome grow older, the ability of the pancreas to produce digestive enzymes may improve slightly, potentially leading to an improvement in the absorption of certain nutrients and relief of symptoms associated with malabsorption. For example, in almost 50 percent of cases, older children may begin to have normal stool patterns. However, even with improved absorption of nutrients and acceptable weight gain, most affected children will be smaller than average for their ages. Shwachman syndrome is also characterized by abnormalities of the soft tissue within bone, called bone marrow. Red bone marrow, which is found within the cavities of all bones at birth, contains immature cells known as stem cells that develop into the three cellular components of the blood. These include red blood cells, which carry oxygen to the cells of the body; white blood cells, which are involved in fighting off infections; and platelets, which help the blood to clot properly. In Shwachman syndrome, bone marrow dysfunction results in impaired production of blood cells. Almost all individuals with Shwachman syndrome have an abnormally decreased number of certain white blood cells (neutrophils). Called “neutropenia,” this condition may be persistent (chronic) or occur occasionally (paroxysmal). In extremely rare cases, neutropenia may occur in regular, predictable cycles (cyclic neutropenia). Neutrophils play an essential role in fighting bacterial infections by detecting, engulfing, and digesting invading bacteria (phagocytosis). In neutropenia associated with Shwachman syndrome, not only may there be an abnormally low number of neutrophils, but those that are present may have an impaired ability to detect and appropriately respond to invading bacteria (impaired chemotaxis). As a result, affected individuals with neutropenia may be prone to repeated bacterial infections including respiratory infections (e.g., pneumonia); infections of the middle ear (otitis media); and repeated bacterial infections of other areas of the body. Although most young children with Shwachman syndrome are prone to such repeated bacterial infections, such susceptibility may vary from case to case, depending upon the degree of neutropenia and other immune factors that help the body to fight off infections. Affected individuals with neutropenia may also have additional abnormalities believed to result from an increased susceptibility to infections. These may include increased tooth decay (dental caries), mouth ulcers, and/or disease of the tissues that surround and support the teeth (periodontal disease). The bone marrow dysfunction associated with Shwachman syndrome may result in abnormalities in the production of other types of blood cells. In some cases, affected individuals have a reduced number of circulating blood platelets (thrombocytopenia), which play an important role in clotting the blood. Individuals with thrombocytopenia may bruise easily and, without appropriate precautions, be prone to abnormal bleeding; however, episodes of severe bleeding are rare. In approximately half of individuals with Shwachman syndrome, there may be abnormally low levels of red blood cells (anemia). Because red blood cells contain hemoglobin, which functions to carry oxygen, low levels of red blood cells may result in an impaired ability to transport oxygen from the lungs to tissues throughout the body. Associated symptoms may include fatigue, abnormal paleness of the skin (pallor), and/or other findings. In addition, in some cases, failure of the bone marrow's cell-generating capacity leads to pancytopenia or decreased levels of all cellular components of the blood, potentially in association with myelodysplastic syndrome (MDS). MDS refers to bone marrow disorders characterized by abnormal stem cells and low levels of red blood cells, white blood cells, and platelets. MDS may precede the development of acute myeloid leukemia, a cancer in which cells that normally develop into certain white blood cells (granulocytes) become malignant and abnormally proliferate. Only approximately one-third of children with Shwachman syndrome eventually develop one of these conditions. Approximately half of individuals with Shwachman syndrome also have abnormal bone changes that may affect the rib cage and/or bones in the arms and/or legs (limbs). For example, some affected individuals may have abnormal thickening of the ribs and their supporting connective tissue (costochondral thickening), resulting in abnormally short, flared ribs. In addition, in rare cases, abnormal narrowness of the rib cage may cause difficulties with breathing during infancy; however, such symptoms may improve later in childhood. In cases where limb bone changes occur, the region where the long shaft of the bone (diaphysis) meets its growing end (epiphysis) may develop improperly (metaphyseal dysostosis). In most cases, metaphyseal dysostosis has no harmful effects. However, abnormal bone development (improper ossification) may cause growth delay in a particular bone. Such abnormalities may affect particular areas such as the thigh bone (femur) or the shin bone (tibia). For example, such changes may cause an abnormal reduction in the angle of the thigh bone or the knee, potentially resulting in shortening of the leg, stiffness, and/or limping. In rare cases, individuals with Shwachman syndrome may have additional skeletal malformations such as fingers that are abnormally bent (clinodactyly). Some affected infants may also have delays in tooth eruption, and their teeth may develop improperly (dental dysplasia). Another primary characteristic often associated with Shwachman syndrome is short stature. At birth, affected infants are usually of normal height and weight. However, shortly after birth, growth slows and, by the first year of life, most children are below average for height and weight. Most children continue to grow and gain weight at a normal rate but remain smaller than average. The severity of the abnormality varies greatly from case to case. Although malabsorption due to pancreatic insufficiency may cause secondary problems with growth and nutrition, short stature appears to be one of the many primary manifestations of Shwachman syndrome. Some affected children may also have an abnormally large liver (hepatomegaly) and/or increased levels of certain liver enzymes in the blood (serum liver enzymes). In addition, in some rare cases, those with the disorder may be affected by renal tubular acidosis, a condition in which there is insufficient removal of acid from the blood by the kidney (renal) tubules for excretion in the urine. The renal tubules are part of the filtering units of the kidneys (nephrons). Renal tubular acidosis may lead to increased acid levels in the blood, low blood potassium levels, abnormal calcium deposits within functional tissue (parenchyma) of the kidneys (nephrocalcinosis), softening of bones (osteomalacia), and/or other findings. Some individuals with Shwachman syndrome may also have additional physical abnormalities. For example, many may exhibit abnormally decreased saliva production, though such symptoms do not appear to contribute to digestive abnormalities. In addition, in early childhood, some with the disorder may have various skin abnormalities including rashes and/or skin that is scaly, dry, and/or rough (ichthyosiform lesions). In many cases, the skin abnormalities may decrease or cease during later childhood. In rare cases, individuals with Shwachman syndrome may have heart (cardiac) abnormalities. For example, some affected individuals may have abnormal enlargement of the right side of the heart (right-sided hypertrophy). In addition, per reports in the medical literature, children with Shwachman syndrome in a small population in Finland have had an abnormally increased incidence of heart muscle (myocardial) abnormalities as a secondary characteristic in association with the disorder. In such cases, the abnormal formation of scar tissue within heart muscle (myocardial fibrosis) may result in tissue damage and loss (necrosis) in certain areas of the heart (e.g., left ventricle), potentially resulting in life-threatening complications (e.g., heart failure). However, researchers have not observed such patterns of myocardial fibrosis in children with Shwachman syndrome in other geographic locations. In extremely rare cases, individuals with Shwachman syndrome may also have nervous system abnormalities. These may include an impaired ability to perform certain voluntary movements (apraxia), low muscle tone (hypotonia), and/or general weakness. In addition, in some cases, children with Shwachman syndrome may experience a delay in reaching developmental milestones (such as crawling, sitting, walking, learning to speak, etc. [delayed motor and speech development]); however, by school age, affected children usually reach their expected milestones. Most children with Shwachman syndrome have normal intelligence; however, in some cases, affected children may have a below-normal I.Q.
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Shwachman Diamond Syndrome
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Causes of Shwachman Diamond Syndrome
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Shwachman syndrome is most likely inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. Researchers at The Hospital for Sick Children and the University of Toronto in Canada have identified the gene that is altered in Shwachman syndrome. After studying 250 affected families from around the world, they identified two major disease-causing mutations in the SBDS gene on chromosome 7. The function of SBDS gene is currently unknown. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p”, a long arm identified by the letter “q”, and a narrowed region at which the two arms are joined (centromere). Chromosomes are further subdivided into bands that are numbered. Some evidence suggests that an increased predisposition to the development of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) may potentially be associated with structural abnormalities of chromosome 7 (e.g., chromosome 7 monosomy or deletion of all or a portion of the long arm [q] of chromosome 7). Investigators have detected isochromosome 7q in a few individuals with Shwachman syndrome affected by the development of MDS and AML. (An isochromosome is an abnormal chromosome with identical arms on each side of the centromere.) However isochromosome 7q has been reported in association with Shwachman syndrome without clinical signs of MDS and AML and a child with Shwachman syndrome and a chromosome 7 abnormality will not necessarily develop MDS or AML. Research is ongoing to determine the cause of MDS and AML in association with Shwachman syndrome. (For more information on these disorders, choose “myelodysplastic syndromes” or “leukemia” as your search terms in the Rare Disease Database.)
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Causes of Shwachman Diamond Syndrome. Shwachman syndrome is most likely inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. Researchers at The Hospital for Sick Children and the University of Toronto in Canada have identified the gene that is altered in Shwachman syndrome. After studying 250 affected families from around the world, they identified two major disease-causing mutations in the SBDS gene on chromosome 7. The function of SBDS gene is currently unknown. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p”, a long arm identified by the letter “q”, and a narrowed region at which the two arms are joined (centromere). Chromosomes are further subdivided into bands that are numbered. Some evidence suggests that an increased predisposition to the development of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) may potentially be associated with structural abnormalities of chromosome 7 (e.g., chromosome 7 monosomy or deletion of all or a portion of the long arm [q] of chromosome 7). Investigators have detected isochromosome 7q in a few individuals with Shwachman syndrome affected by the development of MDS and AML. (An isochromosome is an abnormal chromosome with identical arms on each side of the centromere.) However isochromosome 7q has been reported in association with Shwachman syndrome without clinical signs of MDS and AML and a child with Shwachman syndrome and a chromosome 7 abnormality will not necessarily develop MDS or AML. Research is ongoing to determine the cause of MDS and AML in association with Shwachman syndrome. (For more information on these disorders, choose “myelodysplastic syndromes” or “leukemia” as your search terms in the Rare Disease Database.)
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Shwachman Diamond Syndrome
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Affects of Shwachman Diamond Syndrome
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Shwachman syndrome is a rare genetic disorder that may be apparent at birth (congenital), during early infancy, or within the first few years of life. In rare cases, the diagnosis may be made during adolescence or adulthood. Reports indicate that the disorder affects males and females by a ratio of approximately 1.7 to 1. In addition to the name Shwachman syndrome, alternative terms for the disorder include Shwachman-Bodian syndrome and Shwachman-Diamond-Oski syndrome. These terms are derived from the names of several investigators who described the disease entity in 1964. Since then, well over 100 cases have been recorded in the medical literature. Reported estimates concerning the disorder's incidence have varied, ranging from one in every 20,000 births to one in 200,000 births. (Incidence refers to the number of new cases of a particular disorder or condition during a specific period.) Because the disorder varies in severity from case to case and since there is no one test to make a diagnosis, it is difficult to determine the true frequency of Shwachman syndrome in the general population.
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Affects of Shwachman Diamond Syndrome. Shwachman syndrome is a rare genetic disorder that may be apparent at birth (congenital), during early infancy, or within the first few years of life. In rare cases, the diagnosis may be made during adolescence or adulthood. Reports indicate that the disorder affects males and females by a ratio of approximately 1.7 to 1. In addition to the name Shwachman syndrome, alternative terms for the disorder include Shwachman-Bodian syndrome and Shwachman-Diamond-Oski syndrome. These terms are derived from the names of several investigators who described the disease entity in 1964. Since then, well over 100 cases have been recorded in the medical literature. Reported estimates concerning the disorder's incidence have varied, ranging from one in every 20,000 births to one in 200,000 births. (Incidence refers to the number of new cases of a particular disorder or condition during a specific period.) Because the disorder varies in severity from case to case and since there is no one test to make a diagnosis, it is difficult to determine the true frequency of Shwachman syndrome in the general population.
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Shwachman Diamond Syndrome
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Related disorders of Shwachman Diamond Syndrome
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Some of the symptoms of the following disorders may be similar to those seen in Shwachman syndrome. Comparisons may be useful for a differential diagnosis: Cystic fibrosis is an inherited disorder that affects many exocrine (“outward-secreting”) glands of the body, including the sweat glands, salivary glands, and those within the pancreas and respiratory system. In individuals with the disorder, glands within the lining of tubular air passages (bronchi) in the lungs produce unusually thick, sticky secretions of mucus, clogging and obstructing the air passages. In addition, the pancreas lacks the sufficient amount of digestive enzymes required to break down food and absorb fats and nutrients properly (pancreatic insufficiency). The sweat and salivary glands may function abnormally as well. Symptoms of cystic fibrosis may include failure to thrive; intestinal blockage (meconium ileus); loose, foul smelling stools that contain an excessive amount of fat (steatorrhea); chronic cough; an increased susceptibility to repeated lung infections; and/or abnormally salty sweat containing elevated levels of chloride and sodium. Cystic fibrosis is inherited as an autosomal recessive trait. (For more information on this disorder, choose “cystic fibrosis” as your search term in the Rare Disease Database.) Pearson marrow-pancreas syndrome is an extremely rare disorder in which red blood cells have an impaired ability to carry oxygen (sideroblastic anemia). Additional characteristics include abnormal accumulation of scar tissue (fibrosis) within the pancreas, impaired absorption of necessary nutrients during digestion (malabsorption), and the formation of abnormal cavities within the bone marrow (vacuolization). Affected individuals may have a low birth weight, failure to grow at the expected rate during infancy (failure to thrive), wasting away (atrophy) or absence of the spleen (asplenia), and/or abnormally high levels of lactic acid in the blood (lactic acidosis). Pearson marrow-pancreas syndrome may be caused by changes in genetic material (mutations) that affect the function of mitochondria. Kostmann's syndrome, also known as genetic infantile agranulocytosis, is a rare inherited bone marrow disorder. Associated features include persistent, extremely low levels of circulating neutrophils (neutropenia), frequent bacterial infections, and an increased susceptibility to developing myelodysplastic syndrome and acute myeloid leukemia. Kostmann's syndrome is usually inherited as an autosomal recessive condition, but autosomal dominant and X-linked inheritance have also been reported.Johanson-Blizzard syndrome (JBS) is a rare genetic disorder that may be apparent at birth or early childhood. Associated symptoms and findings may vary greatly from case to case. However, characteristic features include insufficient intestinal absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency); failure to grow and gain weight at the expected rate (failure to thrive) during the first years of life, contributing to short stature; distinctive abnormalities of the skull and facial (craniofacial) region; hearing impairment due to inner ear abnormalities (sensorineural hearing loss); and/or intellectual disability. Approximately one third of affected infants may also have abnormally decreased activity of the thyroid gland and underproduction of thyroid hormones (hypothyroidism). Distinctive craniofacial abnormalities may include an unusually small nose that appears “beak shaped” due to absence (aplasia) or underdevelopment (hypoplasia) of the nostrils (nasal alae); small, malformed primary (deciduous) teeth and misshapen or absent secondary (permanent) teeth; unusually sparse, coarse scalp hair that tends to have a distinctive “upsweep” in the forehead area; an unusually small head (microcephaly); and/or other features. In some cases, additional abnormalities may also be present. Johanson-Blizzard syndrome is inherited as an autosomal recessive trait. (For further information, please choose “Johanson Blizzard” as your search term in the Rare Disease Database.) Metaphyseal chondrodysplasia (McKusick type) is a rare inherited disorder characterized by progressive, short-limbed dwarfism due to abnormal development of the cartilage at the ends of long bones; hair that is abnormally fine and sparse; and/or impaired functioning of certain cells that play an important role in helping the body's immune system to fight infection (cellular immunodeficiency). Additional features may include improper absorption of necessary nutrients (malabsorption); a chronic decrease in certain white blood cells (neutropenia and lymphopenia); low levels of red blood cells (anemia); dental abnormalities; and/or other findings. Metaphyseal chondrodysplasia (McKusick type) is inherited as an autosomal recessive trait. (For more information on this disorder, choose “metaphyseal chondrodysplasia ” as your search term in the Rare Disease Database.) There are additional disorders that may be characterized by various blood (hematological) abnormalities such as neutropenia, thrombocytopenia, and/or anemia occurring in association with other findings that may be similar to those potentially associated with Shwachman syndrome. (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 Shwachman Diamond Syndrome. Some of the symptoms of the following disorders may be similar to those seen in Shwachman syndrome. Comparisons may be useful for a differential diagnosis: Cystic fibrosis is an inherited disorder that affects many exocrine (“outward-secreting”) glands of the body, including the sweat glands, salivary glands, and those within the pancreas and respiratory system. In individuals with the disorder, glands within the lining of tubular air passages (bronchi) in the lungs produce unusually thick, sticky secretions of mucus, clogging and obstructing the air passages. In addition, the pancreas lacks the sufficient amount of digestive enzymes required to break down food and absorb fats and nutrients properly (pancreatic insufficiency). The sweat and salivary glands may function abnormally as well. Symptoms of cystic fibrosis may include failure to thrive; intestinal blockage (meconium ileus); loose, foul smelling stools that contain an excessive amount of fat (steatorrhea); chronic cough; an increased susceptibility to repeated lung infections; and/or abnormally salty sweat containing elevated levels of chloride and sodium. Cystic fibrosis is inherited as an autosomal recessive trait. (For more information on this disorder, choose “cystic fibrosis” as your search term in the Rare Disease Database.) Pearson marrow-pancreas syndrome is an extremely rare disorder in which red blood cells have an impaired ability to carry oxygen (sideroblastic anemia). Additional characteristics include abnormal accumulation of scar tissue (fibrosis) within the pancreas, impaired absorption of necessary nutrients during digestion (malabsorption), and the formation of abnormal cavities within the bone marrow (vacuolization). Affected individuals may have a low birth weight, failure to grow at the expected rate during infancy (failure to thrive), wasting away (atrophy) or absence of the spleen (asplenia), and/or abnormally high levels of lactic acid in the blood (lactic acidosis). Pearson marrow-pancreas syndrome may be caused by changes in genetic material (mutations) that affect the function of mitochondria. Kostmann's syndrome, also known as genetic infantile agranulocytosis, is a rare inherited bone marrow disorder. Associated features include persistent, extremely low levels of circulating neutrophils (neutropenia), frequent bacterial infections, and an increased susceptibility to developing myelodysplastic syndrome and acute myeloid leukemia. Kostmann's syndrome is usually inherited as an autosomal recessive condition, but autosomal dominant and X-linked inheritance have also been reported.Johanson-Blizzard syndrome (JBS) is a rare genetic disorder that may be apparent at birth or early childhood. Associated symptoms and findings may vary greatly from case to case. However, characteristic features include insufficient intestinal absorption (malabsorption) of fats and other nutrients due to abnormal development of the pancreas (pancreatic insufficiency); failure to grow and gain weight at the expected rate (failure to thrive) during the first years of life, contributing to short stature; distinctive abnormalities of the skull and facial (craniofacial) region; hearing impairment due to inner ear abnormalities (sensorineural hearing loss); and/or intellectual disability. Approximately one third of affected infants may also have abnormally decreased activity of the thyroid gland and underproduction of thyroid hormones (hypothyroidism). Distinctive craniofacial abnormalities may include an unusually small nose that appears “beak shaped” due to absence (aplasia) or underdevelopment (hypoplasia) of the nostrils (nasal alae); small, malformed primary (deciduous) teeth and misshapen or absent secondary (permanent) teeth; unusually sparse, coarse scalp hair that tends to have a distinctive “upsweep” in the forehead area; an unusually small head (microcephaly); and/or other features. In some cases, additional abnormalities may also be present. Johanson-Blizzard syndrome is inherited as an autosomal recessive trait. (For further information, please choose “Johanson Blizzard” as your search term in the Rare Disease Database.) Metaphyseal chondrodysplasia (McKusick type) is a rare inherited disorder characterized by progressive, short-limbed dwarfism due to abnormal development of the cartilage at the ends of long bones; hair that is abnormally fine and sparse; and/or impaired functioning of certain cells that play an important role in helping the body's immune system to fight infection (cellular immunodeficiency). Additional features may include improper absorption of necessary nutrients (malabsorption); a chronic decrease in certain white blood cells (neutropenia and lymphopenia); low levels of red blood cells (anemia); dental abnormalities; and/or other findings. Metaphyseal chondrodysplasia (McKusick type) is inherited as an autosomal recessive trait. (For more information on this disorder, choose “metaphyseal chondrodysplasia ” as your search term in the Rare Disease Database.) There are additional disorders that may be characterized by various blood (hematological) abnormalities such as neutropenia, thrombocytopenia, and/or anemia occurring in association with other findings that may be similar to those potentially associated with Shwachman syndrome. (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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Shwachman Diamond Syndrome
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nord_1117_5
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Diagnosis of Shwachman Diamond Syndrome
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Shwachman syndrome is usually diagnosed at birth or during early childhood based upon a thorough clinical evaluation, characteristic physical findings, and specialized tests. In rare cases, the diagnosis may be made during adolescence or adulthood.Testing to detect the mutated gene that causes Shwachman syndrome is available to confirm a diagnosis.When steatorrhea is present without chronic respiratory abnormalities, a sweat test may be performed to help exclude a possible diagnosis of cystic fibrosis. A sweat test measures the concentration of sodium and chloride excreted from the sweat glands. Although individuals with Shwachman syndrome and cystic fibrosis may have certain similar symptoms (e.g., steatorrhea and other findings associated with pancreatic insufficiency and malabsorption), individuals with Shwachman syndrome have normal concentrations of electrolytes in their sweat, while those with cystic fibrosis have abnormally elevated concentrations of sodium and chloride. (For more on this disorder, see the "Related Disorders" section above.)In addition, several specialized imaging tests may be used to confirm the presence of specific abnormalities potentially associated with Shwachman syndrome. Pancreatic abnormalities, such as fatty infiltration (pancreatic lipomatosis), may be demonstrated by computed tomography (CT) scanning, abdominal ultrasound, and/or magnetic resonance imaging (MRI). During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of an organ's tissue structure. In ultrasonography, reflected sound waves create an image of the organs in question. MRI uses a magnetic field and radio waves to create cross-sectional images of the organ.Various specialized tests of the pancreas may also be performed to help confirm pancreatic insufficiency. Such tests may include stool tests, blood tests, and/or analysis of secretions from the pancreas that are released into the duodenum. (The duodenum is the first portion of the small intestine.)Bone marrow dysfunction may be confirmed and characterized by the removal and microscopic examination of fluid and tissue samples (bone marrow aspiration and biopsy) as well as blood studies. Various specialized analyses may be conducted on bone marrow fluid and tissue samples, including measures to identify myelodysplastic changes and chromosomal studies to detect structural abnormalities of chromosome 7 (e.g., monosomy 7, monosomy 7q, isochromosome 7q). As mentioned above, bone marrow dysfunction in those with Shwachman syndrome may manifest at different times by varying combinations of neutropenia, thrombocytopenia, and/or anemia. Hematological problems due to bone marrow dysfunction may be monitored by tests that measure the various types of blood cells in the circulation.Skeletal abnormalities potentially occurring in association with Shwachman syndrome (e.g., metaphyseal dysostosis and rib cage abnormalities) may be identified by physical examination and specialized X-ray studies. In some cases, additional diagnostic tests may also be conducted to detect, characterize, and/or monitor certain abnormalities potentially associated with the disorder.
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Diagnosis of Shwachman Diamond Syndrome. Shwachman syndrome is usually diagnosed at birth or during early childhood based upon a thorough clinical evaluation, characteristic physical findings, and specialized tests. In rare cases, the diagnosis may be made during adolescence or adulthood.Testing to detect the mutated gene that causes Shwachman syndrome is available to confirm a diagnosis.When steatorrhea is present without chronic respiratory abnormalities, a sweat test may be performed to help exclude a possible diagnosis of cystic fibrosis. A sweat test measures the concentration of sodium and chloride excreted from the sweat glands. Although individuals with Shwachman syndrome and cystic fibrosis may have certain similar symptoms (e.g., steatorrhea and other findings associated with pancreatic insufficiency and malabsorption), individuals with Shwachman syndrome have normal concentrations of electrolytes in their sweat, while those with cystic fibrosis have abnormally elevated concentrations of sodium and chloride. (For more on this disorder, see the "Related Disorders" section above.)In addition, several specialized imaging tests may be used to confirm the presence of specific abnormalities potentially associated with Shwachman syndrome. Pancreatic abnormalities, such as fatty infiltration (pancreatic lipomatosis), may be demonstrated by computed tomography (CT) scanning, abdominal ultrasound, and/or magnetic resonance imaging (MRI). During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of an organ's tissue structure. In ultrasonography, reflected sound waves create an image of the organs in question. MRI uses a magnetic field and radio waves to create cross-sectional images of the organ.Various specialized tests of the pancreas may also be performed to help confirm pancreatic insufficiency. Such tests may include stool tests, blood tests, and/or analysis of secretions from the pancreas that are released into the duodenum. (The duodenum is the first portion of the small intestine.)Bone marrow dysfunction may be confirmed and characterized by the removal and microscopic examination of fluid and tissue samples (bone marrow aspiration and biopsy) as well as blood studies. Various specialized analyses may be conducted on bone marrow fluid and tissue samples, including measures to identify myelodysplastic changes and chromosomal studies to detect structural abnormalities of chromosome 7 (e.g., monosomy 7, monosomy 7q, isochromosome 7q). As mentioned above, bone marrow dysfunction in those with Shwachman syndrome may manifest at different times by varying combinations of neutropenia, thrombocytopenia, and/or anemia. Hematological problems due to bone marrow dysfunction may be monitored by tests that measure the various types of blood cells in the circulation.Skeletal abnormalities potentially occurring in association with Shwachman syndrome (e.g., metaphyseal dysostosis and rib cage abnormalities) may be identified by physical examination and specialized X-ray studies. In some cases, additional diagnostic tests may also be conducted to detect, characterize, and/or monitor certain abnormalities potentially associated with the disorder.
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Therapies of Shwachman Diamond Syndrome
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TreatmentThe treatment of Shwachman syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected child's treatment. Such specialists may include pediatricians; physicians who specialize in disorders of the endocrine glands (endocrinologists); physicians who diagnose and treat disorders of the digestive system (gastroenterologists); specialists who diagnose and treat skeletal abnormalities (orthopedists); physicians specializing in blood disorders (hematologists); dentists; surgeons; physical therapists; dietitians; and/or other health care professionals.Affected individuals with pancreatic insufficiency may require pancreatic enzyme supplements with meals to promote proper absorption of fats and other necessary nutrients during digestion. In many cases, vitamin supplements (e.g., fat-soluble vitamins A, D, E, K) may also be prescribed to prevent or treat vitamin deficiencies that may result from malabsorption due to pancreatic insufficiency. A high-protein and/or high-calorie diet may also be prescribed in some cases to ensure that an affected individual's total nutritional requirements are met.In addition, physicians may regularly monitor affected individuals for hematological abnormalities associated with bone marrow dysfunction (e.g., regular blood counts) to ensure proper preventive measures and early, prompt treatment. For example, for affected individuals with thrombocytopenia, dentists and other health care workers may recommend certain preventive measures before or during dental work or surgery (e.g., certain medications) to prevent or lower the risk of abnormal, uncontrolled bleeding.In some severe cases of neutropenia, anemia, and/or thrombocytopenia, transfusions of specific blood components may be given to help reduce associated symptoms.As mentioned above, some individuals with Shwachman syndrome may be more prone to developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is suspected that the incidence of leukemia may be increased in those with persistent blood abnormalities. Therefore, physicians will closely monitor an affected individual's hematological status to ensure early detection and prompt, appropriate treatment. Physicians may also conduct periodic cytogenetic evaluations to detect certain structural abnormalities of chromosome 7 that may be potentially associated with MDS or AML.Because neutropenia may result in an increased susceptibility to bacterial infections, physicians may closely monitor affected individuals, recommend preventive measures, and institute immediate antibiotic treatment should such infections occur. In severe cases of bacterial infection, hospitalization may be required.Individuals with Shwachman syndrome who experience recurrent infections and persistently low neutrophil counts (neutropenia) may be treated with granulocyte-colony stimulating factor (G-CSF). G-CSF is a growth factor; it stimulates the production of white blood cells. The decision to use G-CSF should be made after close consultation with a child's physician and medical team.As noted above, affected individuals with neutropenia may also be prone to tooth decay and periodontal disease. In such cases, dentists and other specialists may recommend special preventive steps or treatment for these conditions.Various orthopedic measures may also be taken to help treat and/or correct the skeletal abnormalities potentially associated with Shwachman syndrome. For example, abnormal bone changes causing a reduction in the angle of the thigh bone or the knee may be closely monitored to ensure appropriate, early orthopedic treatment. In severe cases, surgery (e.g., osteotomy) may be performed to help correct the angle from the head (ball) and neck of the thigh bone to its shaft, thereby reducing stiffness and enabling affected individuals to walk with less discomfort.In some cases, early intervention may be important in ensuring that children with Shwachman syndrome reach their potential. Special services that may be beneficial include speech therapy (in cases of hearing impairment due to otitis media) and other medical, social, and/or vocational services.Genetic counseling may be of benefit for affected individuals, their immediate families, and other relatives. Other treatment is symptomatic and supportive.
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Therapies of Shwachman Diamond Syndrome. TreatmentThe treatment of Shwachman syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected child's treatment. Such specialists may include pediatricians; physicians who specialize in disorders of the endocrine glands (endocrinologists); physicians who diagnose and treat disorders of the digestive system (gastroenterologists); specialists who diagnose and treat skeletal abnormalities (orthopedists); physicians specializing in blood disorders (hematologists); dentists; surgeons; physical therapists; dietitians; and/or other health care professionals.Affected individuals with pancreatic insufficiency may require pancreatic enzyme supplements with meals to promote proper absorption of fats and other necessary nutrients during digestion. In many cases, vitamin supplements (e.g., fat-soluble vitamins A, D, E, K) may also be prescribed to prevent or treat vitamin deficiencies that may result from malabsorption due to pancreatic insufficiency. A high-protein and/or high-calorie diet may also be prescribed in some cases to ensure that an affected individual's total nutritional requirements are met.In addition, physicians may regularly monitor affected individuals for hematological abnormalities associated with bone marrow dysfunction (e.g., regular blood counts) to ensure proper preventive measures and early, prompt treatment. For example, for affected individuals with thrombocytopenia, dentists and other health care workers may recommend certain preventive measures before or during dental work or surgery (e.g., certain medications) to prevent or lower the risk of abnormal, uncontrolled bleeding.In some severe cases of neutropenia, anemia, and/or thrombocytopenia, transfusions of specific blood components may be given to help reduce associated symptoms.As mentioned above, some individuals with Shwachman syndrome may be more prone to developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is suspected that the incidence of leukemia may be increased in those with persistent blood abnormalities. Therefore, physicians will closely monitor an affected individual's hematological status to ensure early detection and prompt, appropriate treatment. Physicians may also conduct periodic cytogenetic evaluations to detect certain structural abnormalities of chromosome 7 that may be potentially associated with MDS or AML.Because neutropenia may result in an increased susceptibility to bacterial infections, physicians may closely monitor affected individuals, recommend preventive measures, and institute immediate antibiotic treatment should such infections occur. In severe cases of bacterial infection, hospitalization may be required.Individuals with Shwachman syndrome who experience recurrent infections and persistently low neutrophil counts (neutropenia) may be treated with granulocyte-colony stimulating factor (G-CSF). G-CSF is a growth factor; it stimulates the production of white blood cells. The decision to use G-CSF should be made after close consultation with a child's physician and medical team.As noted above, affected individuals with neutropenia may also be prone to tooth decay and periodontal disease. In such cases, dentists and other specialists may recommend special preventive steps or treatment for these conditions.Various orthopedic measures may also be taken to help treat and/or correct the skeletal abnormalities potentially associated with Shwachman syndrome. For example, abnormal bone changes causing a reduction in the angle of the thigh bone or the knee may be closely monitored to ensure appropriate, early orthopedic treatment. In severe cases, surgery (e.g., osteotomy) may be performed to help correct the angle from the head (ball) and neck of the thigh bone to its shaft, thereby reducing stiffness and enabling affected individuals to walk with less discomfort.In some cases, early intervention may be important in ensuring that children with Shwachman syndrome reach their potential. Special services that may be beneficial include speech therapy (in cases of hearing impairment due to otitis media) and other medical, social, and/or vocational services.Genetic counseling may be of benefit for affected individuals, their immediate families, and other relatives. Other treatment is symptomatic and supportive.
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Overview of Sialadenitis
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Sialadenitis is a condition characterized by inflammation and enlargement of one or more of the salivary glands, the glands that secrete saliva into the mouth. There are both acute and chronic forms. Sialadenitis is often associated with pain, tenderness, redness, and gradual, localized swelling of the affected area. The exact cause of sialadenitis is not known.
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Overview of Sialadenitis. Sialadenitis is a condition characterized by inflammation and enlargement of one or more of the salivary glands, the glands that secrete saliva into the mouth. There are both acute and chronic forms. Sialadenitis is often associated with pain, tenderness, redness, and gradual, localized swelling of the affected area. The exact cause of sialadenitis is not known.
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Symptoms of Sialadenitis
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Symptoms of sialadenitis include enlargement, tenderness, and redness of one or more salivary glands. These are the glands in the mouth, located near the ear (parotid), under the tongue (sublingual), and under the jaw bone (submaxillary), plus numerous small glands in the tongue, lips, cheeks and palate. Salivary stones (calculi) may block secretions from any of these glands. The gland may sometimes become infected, leading to fever and other complications. Decreased salivary flow is a hallmark of both the acute and chronic forms of sialadenitis. The pain is more obvious while eating, and more than three-quarters of patients complain of dry mouth (xerostomia).
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Symptoms of Sialadenitis. Symptoms of sialadenitis include enlargement, tenderness, and redness of one or more salivary glands. These are the glands in the mouth, located near the ear (parotid), under the tongue (sublingual), and under the jaw bone (submaxillary), plus numerous small glands in the tongue, lips, cheeks and palate. Salivary stones (calculi) may block secretions from any of these glands. The gland may sometimes become infected, leading to fever and other complications. Decreased salivary flow is a hallmark of both the acute and chronic forms of sialadenitis. The pain is more obvious while eating, and more than three-quarters of patients complain of dry mouth (xerostomia).
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Causes of Sialadenitis
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The exact cause of sialadenitis is unknown. In some cases, the condition may be associated with the formation of salivary gland stones (sialolithiasis).
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Causes of Sialadenitis. The exact cause of sialadenitis is unknown. In some cases, the condition may be associated with the formation of salivary gland stones (sialolithiasis).
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Affects of Sialadenitis
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Sialadenitis affects males and females in equal numbers. It shows no racial biases.
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Affects of Sialadenitis. Sialadenitis affects males and females in equal numbers. It shows no racial biases.
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Related disorders of Sialadenitis
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Mikulicz Syndrome is a benign chronic lymphocytic infiltration and enlargement of the tonsils and salivary glands near the ear (parotid gland), beneath the upper jaw bone (submaxillary), tear (lacrimal) and other glands. This condition causes excessive dryness of the mouth and eyes and is often related to Sjogren's Syndrome. (For more information on this disorder, choose “Mikulicz” as your search term in the Rare Disease Database.)Sjogren Syndrome is a degeneration of the tear and salivary glands that may be associated with arthritis. Patients often complain of a gritty, burning sensation in their eyes due to loss of lubrication. When their mouths become dry, chewing and swallowing food is difficult. The lack of saliva causes particles of food to stick to the cheeks, gums, and throat. Other symptoms may include a weak voice, dental decay, dryness of the nose, skin and vagina. (For more information on this disorder, choose “Sjogren” as your search term in the Rare Disease Database.)Mixed Tumor of the Salivary Gland (Pleomorphic Adenoma of the Salivary Gland) is a slowly growing, benign tumor of unknown origin. It is usually located in the parotid salivary glands. Onset of the disorder is slow, but later the tumor tends to grow rapidly. Paralysis of the facial muscles is a rare complication. Sometimes pain occurs in conjunction with the tumor. This disorder tends to be familial and can occur in multiple family members.Periodic Sialadenosis (Periodic Sialorrhea, or Recurring Salivary Adenitis) is a disorder of unknown cause, possibly of autosomal dominant inheritance. It is characterized by sudden discomfort in the region of the salivary glands near the ear and jaws. An unusually large flow of saliva may occur. The outer ear sometimes appears distorted.
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Related disorders of Sialadenitis. Mikulicz Syndrome is a benign chronic lymphocytic infiltration and enlargement of the tonsils and salivary glands near the ear (parotid gland), beneath the upper jaw bone (submaxillary), tear (lacrimal) and other glands. This condition causes excessive dryness of the mouth and eyes and is often related to Sjogren's Syndrome. (For more information on this disorder, choose “Mikulicz” as your search term in the Rare Disease Database.)Sjogren Syndrome is a degeneration of the tear and salivary glands that may be associated with arthritis. Patients often complain of a gritty, burning sensation in their eyes due to loss of lubrication. When their mouths become dry, chewing and swallowing food is difficult. The lack of saliva causes particles of food to stick to the cheeks, gums, and throat. Other symptoms may include a weak voice, dental decay, dryness of the nose, skin and vagina. (For more information on this disorder, choose “Sjogren” as your search term in the Rare Disease Database.)Mixed Tumor of the Salivary Gland (Pleomorphic Adenoma of the Salivary Gland) is a slowly growing, benign tumor of unknown origin. It is usually located in the parotid salivary glands. Onset of the disorder is slow, but later the tumor tends to grow rapidly. Paralysis of the facial muscles is a rare complication. Sometimes pain occurs in conjunction with the tumor. This disorder tends to be familial and can occur in multiple family members.Periodic Sialadenosis (Periodic Sialorrhea, or Recurring Salivary Adenitis) is a disorder of unknown cause, possibly of autosomal dominant inheritance. It is characterized by sudden discomfort in the region of the salivary glands near the ear and jaws. An unusually large flow of saliva may occur. The outer ear sometimes appears distorted.
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Diagnosis of Sialadenitis
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The disorder is often diagnosed by means of a thorough patient history and physical examination. Recent advances in endoscopic equipment make the diagnosis somewhat easier.
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Diagnosis of Sialadenitis. The disorder is often diagnosed by means of a thorough patient history and physical examination. Recent advances in endoscopic equipment make the diagnosis somewhat easier.
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Therapies of Sialadenitis
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TreatmentInitial treatment of sialadenitis involves antibiotic therapy and rehydration of the patient. Patients are referred to specialists (otolaryngologists) if any signs of facial nerve involvement are present or if drainage of the swelling is contemplated. If a stone is present, gentle massage may help move it out of the gland. Otherwise, surgery may be indicated.
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Therapies of Sialadenitis. TreatmentInitial treatment of sialadenitis involves antibiotic therapy and rehydration of the patient. Patients are referred to specialists (otolaryngologists) if any signs of facial nerve involvement are present or if drainage of the swelling is contemplated. If a stone is present, gentle massage may help move it out of the gland. Otherwise, surgery may be indicated.
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Overview of Sialidosis
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Sialidosis, also known as mucolipidosis type I, is a rare inherited metabolic disorder characterized by a deficiency of the enzyme neuraminidase (sometimes referred to as sialidase). Deficiency of neuraminidase results in the abnormal accumulation of toxic materials in the body. Sialidosis is divided into two types (i.e., type I and type II). Sialidosis type I usually becomes apparent during the second decade of life with the development of sudden involuntary muscle contractions (myoclonus), distinctive red spots (cherry-red macules) in the eyes, and sometimes additional neurological findings. Sialidosis type II is usually more severe than sialidosis type I. Type II often begins during infancy or later during childhood and is characterized by cherry-red macules, mildly coarse facial features, skeletal malformations and mild cognitive impairment. Sialidosis is inherited as an autosomal recessive trait.Sialidosis belongs to a group of diseases known as the lysosomal storage disorders (LSDs). Lysosomes are particles bound in membranes within cells that function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as complex molecules composed of a sugar attached to a protein (glycoproteins). In sialidosis patients, low levels or inactivity of the neuraminidase enzyme leads to the abnormal accumulation these compounds in the cells with unwanted consequences. Sialidosis is also classified as one of the mucolipidoses, a subgroup of the LSDs.
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Overview of Sialidosis. Sialidosis, also known as mucolipidosis type I, is a rare inherited metabolic disorder characterized by a deficiency of the enzyme neuraminidase (sometimes referred to as sialidase). Deficiency of neuraminidase results in the abnormal accumulation of toxic materials in the body. Sialidosis is divided into two types (i.e., type I and type II). Sialidosis type I usually becomes apparent during the second decade of life with the development of sudden involuntary muscle contractions (myoclonus), distinctive red spots (cherry-red macules) in the eyes, and sometimes additional neurological findings. Sialidosis type II is usually more severe than sialidosis type I. Type II often begins during infancy or later during childhood and is characterized by cherry-red macules, mildly coarse facial features, skeletal malformations and mild cognitive impairment. Sialidosis is inherited as an autosomal recessive trait.Sialidosis belongs to a group of diseases known as the lysosomal storage disorders (LSDs). Lysosomes are particles bound in membranes within cells that function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as complex molecules composed of a sugar attached to a protein (glycoproteins). In sialidosis patients, low levels or inactivity of the neuraminidase enzyme leads to the abnormal accumulation these compounds in the cells with unwanted consequences. Sialidosis is also classified as one of the mucolipidoses, a subgroup of the LSDs.
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Symptoms of Sialidosis
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The age of onset, symptoms, progression and severity of sialidosis vary greatly from one person to another. Sialidosis type I is a milder form of the disorder than sialidosis type II and has later onset. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.Individuals with sialidosis type I may develop symptoms anywhere from childhood to young adulthood, with most people developing symptoms during the second or third decade of life. Such individuals develop normally until problems with walking (gait disturbances) or vision abnormalities require medical attention. Symptoms of sialidosis type I include the development of distinct red spots in the eyes known as cherry-red macules. Cherry red macules are spots that form on the retina, the thin membrane that lines the back of the eyes. The retinas sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. Affected individuals may experience loss of clarity of vision (visual acuity) and may develop impaired color vision and night blindness. Rapid, involuntary eye movements (nystagmus) and clouding (opacity) of the cornea may also occur.In addition to walking difficulties and vision problems, additional symptoms may be associated with sialidosis type I. Such symptoms include seizures, abnormally heightened reflexes (hyperreflexia), an inability to coordinate voluntary movements (ataxia), and sudden, involuntary twitching or jerking of muscle (myoclonus). Intelligence is usually unaffected in sialidosis type I.Sialidosis type II is generally more severe than sialidosis type I and is often further subdivided into congenital and infantile forms. Some researchers have proposed including a juvenile form, but other researchers believe that these individuals may have galactosialidosis. In the congenital form, symptoms are present at birth. In the infantile form symptoms usually develop shortly after birth.Children with sialidosis type II may develop an abnormally enlarged liver (hepatomegaly) and/or spleen (splenomegaly), a specific assortment of bone deformities known as dysostosis multiplex, coarse facial features, delays in reaching developmental milestones, and cognitive impairment. Bone deformities associated with dysostosis multiplex include premature closure (fusion) of the fibrous joints (sutures) between certain bones of the skull, a thickened skullcap (calvaria), an enlarged skull, widely spaced teeth, thickened collarbones (clavicles), and abnormalities of the ribs, pelvic bones, certain long bones and other bones of the body.Distinctive “coarse” facial features associated with sialidosis type II may include a high forehead, flattened bridge of the nose, a long groove on the upper lip (long philtrum), upturned nostrils (anteverted nares), and puffy eyelids. Some affected children may have overgrowth of the gums (gingival hypertrophy) and an abnormally large tongue (macroglossia).As with sialidosis type I, affected children may also develop clouding (opacity) of the lenses or corneas of the eyes, and sudden, involuntary twitching or jerking of muscles. Cherry-red macules may also develop in children with sialidosis type II.Additional symptoms have been reported in some individuals with sialidosis type II including hearing loss, vision loss, facial swelling due to the accumulation of fluid (facial edema), seizures, an inability to coordinate voluntary movements (ataxia), and heart abnormalities. As children with sialidosis type II age, they may exhibit short stature.Infants with the congenital form may also develop a serious condition in which abnormal amounts of fluid accumulate in various areas of the body (hydrops fetalis). Some infants may experience fluid accumulation in the abdomen (ascites) before birth. The congenital form of sialidosis type II is rapidly progressive and often can cause life-threatening complications early during infancy.
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Symptoms of Sialidosis. The age of onset, symptoms, progression and severity of sialidosis vary greatly from one person to another. Sialidosis type I is a milder form of the disorder than sialidosis type II and has later onset. It is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.Individuals with sialidosis type I may develop symptoms anywhere from childhood to young adulthood, with most people developing symptoms during the second or third decade of life. Such individuals develop normally until problems with walking (gait disturbances) or vision abnormalities require medical attention. Symptoms of sialidosis type I include the development of distinct red spots in the eyes known as cherry-red macules. Cherry red macules are spots that form on the retina, the thin membrane that lines the back of the eyes. The retinas sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. Affected individuals may experience loss of clarity of vision (visual acuity) and may develop impaired color vision and night blindness. Rapid, involuntary eye movements (nystagmus) and clouding (opacity) of the cornea may also occur.In addition to walking difficulties and vision problems, additional symptoms may be associated with sialidosis type I. Such symptoms include seizures, abnormally heightened reflexes (hyperreflexia), an inability to coordinate voluntary movements (ataxia), and sudden, involuntary twitching or jerking of muscle (myoclonus). Intelligence is usually unaffected in sialidosis type I.Sialidosis type II is generally more severe than sialidosis type I and is often further subdivided into congenital and infantile forms. Some researchers have proposed including a juvenile form, but other researchers believe that these individuals may have galactosialidosis. In the congenital form, symptoms are present at birth. In the infantile form symptoms usually develop shortly after birth.Children with sialidosis type II may develop an abnormally enlarged liver (hepatomegaly) and/or spleen (splenomegaly), a specific assortment of bone deformities known as dysostosis multiplex, coarse facial features, delays in reaching developmental milestones, and cognitive impairment. Bone deformities associated with dysostosis multiplex include premature closure (fusion) of the fibrous joints (sutures) between certain bones of the skull, a thickened skullcap (calvaria), an enlarged skull, widely spaced teeth, thickened collarbones (clavicles), and abnormalities of the ribs, pelvic bones, certain long bones and other bones of the body.Distinctive “coarse” facial features associated with sialidosis type II may include a high forehead, flattened bridge of the nose, a long groove on the upper lip (long philtrum), upturned nostrils (anteverted nares), and puffy eyelids. Some affected children may have overgrowth of the gums (gingival hypertrophy) and an abnormally large tongue (macroglossia).As with sialidosis type I, affected children may also develop clouding (opacity) of the lenses or corneas of the eyes, and sudden, involuntary twitching or jerking of muscles. Cherry-red macules may also develop in children with sialidosis type II.Additional symptoms have been reported in some individuals with sialidosis type II including hearing loss, vision loss, facial swelling due to the accumulation of fluid (facial edema), seizures, an inability to coordinate voluntary movements (ataxia), and heart abnormalities. As children with sialidosis type II age, they may exhibit short stature.Infants with the congenital form may also develop a serious condition in which abnormal amounts of fluid accumulate in various areas of the body (hydrops fetalis). Some infants may experience fluid accumulation in the abdomen (ascites) before birth. The congenital form of sialidosis type II is rapidly progressive and often can cause life-threatening complications early during infancy.
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Causes of Sialidosis
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Sialidosis is caused by mutations of the NEU1 gene. This gene mutation is inherited as an autosomal recessive trait. 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.Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.Investigators have determined that the NEU1 gene is located on the short arm (p) of chromosome 6 (6p21.3). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 6p21.3” refers to band 21.3 on the short arm of chromosome 6. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The NEU1 gene contains instructions for creating (encoding) an enzyme known as neuraminidase (alpha-neuraminidase) which is necessary for the proper breakdown (metabolism) of certain glycoproteins, substances that play various vital roles in the body. Glycoproteins are proteins that contain oligosaccharides, which are long sugar chains. Without proper levels of functional neuraminidase, oligosaccharides abnormally accumulate in and damage various tissues and organs of the body. Mutations of the NEU1 gene result in the lack of production of the neuraminidase enzyme or the production of a defective, inactive form of the enzyme.
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Causes of Sialidosis. Sialidosis is caused by mutations of the NEU1 gene. This gene mutation is inherited as an autosomal recessive trait. 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.Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.Investigators have determined that the NEU1 gene is located on the short arm (p) of chromosome 6 (6p21.3). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 6p21.3” refers to band 21.3 on the short arm of chromosome 6. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The NEU1 gene contains instructions for creating (encoding) an enzyme known as neuraminidase (alpha-neuraminidase) which is necessary for the proper breakdown (metabolism) of certain glycoproteins, substances that play various vital roles in the body. Glycoproteins are proteins that contain oligosaccharides, which are long sugar chains. Without proper levels of functional neuraminidase, oligosaccharides abnormally accumulate in and damage various tissues and organs of the body. Mutations of the NEU1 gene result in the lack of production of the neuraminidase enzyme or the production of a defective, inactive form of the enzyme.
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Affects of Sialidosis
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Sialidosis affects males and females in equal numbers. The exact incidence of sialidosis in the general population is unknown. One estimate places the incidence at 1 in 4.2 million individuals in the Australian population. Another estimate placed the incidence at 1-4 individuals per 200,000 of the general population. Because rare disorders like sialidosis often go unrecognized or misdiagnosed, determining the true frequency of sialidosis in the general population is difficult.
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Affects of Sialidosis. Sialidosis affects males and females in equal numbers. The exact incidence of sialidosis in the general population is unknown. One estimate places the incidence at 1 in 4.2 million individuals in the Australian population. Another estimate placed the incidence at 1-4 individuals per 200,000 of the general population. Because rare disorders like sialidosis often go unrecognized or misdiagnosed, determining the true frequency of sialidosis in the general population is difficult.
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Related disorders of Sialidosis
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Symptoms of the following disorders can be similar to those of sialidosis. Comparisons may be useful for a differential diagnosis.Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies. There are nearly 50 of these disorders altogether, and they may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. . While enzyme replacement therapy is available for a number of these disorders there is currently no approved treatment for many lysosomal storage diseases. (For more information on this disorder, choose lysosomal storage disease as your search term in the Rare Disease Database.)Galactosialidosis is a rare inherited metabolic disorder characterized by deficiencies of two separate enzymes neuraminidase and beta-galactosialidase. Symptoms may include severe swelling of many soft tissues of the body and abdominal swelling due to the development of fluid-filled sacs (ascites). Cherry red spots in the eyes, skeletal abnormalities, abnormal enlargement of many organs of the body (visceromegaly), and/or mental retardation may also occur. Growth delays, joint stiffness, and/or coarse facial features are also characteristic of this disorder. Galactosialidosis is inherited as an autosomal recessive genetic trait. The symptoms of this disorder may be very difficult to distinguish from those of sialidosis.
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Related disorders of Sialidosis. Symptoms of the following disorders can be similar to those of sialidosis. Comparisons may be useful for a differential diagnosis.Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies. There are nearly 50 of these disorders altogether, and they may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. . While enzyme replacement therapy is available for a number of these disorders there is currently no approved treatment for many lysosomal storage diseases. (For more information on this disorder, choose lysosomal storage disease as your search term in the Rare Disease Database.)Galactosialidosis is a rare inherited metabolic disorder characterized by deficiencies of two separate enzymes neuraminidase and beta-galactosialidase. Symptoms may include severe swelling of many soft tissues of the body and abdominal swelling due to the development of fluid-filled sacs (ascites). Cherry red spots in the eyes, skeletal abnormalities, abnormal enlargement of many organs of the body (visceromegaly), and/or mental retardation may also occur. Growth delays, joint stiffness, and/or coarse facial features are also characteristic of this disorder. Galactosialidosis is inherited as an autosomal recessive genetic trait. The symptoms of this disorder may be very difficult to distinguish from those of sialidosis.
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Diagnosis of Sialidosis
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A diagnosis of sialidosis is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. An examination of urine may reveal increased levels of oligosaccharides. A urine test is usually followed up by blood tests and a skin biopsy (surgical removal and microscopic study of skin tissue). These tests can reveal low levels of the enzyme alpha-neuraminidase in blood and skin tissue.For families with a previous history of sialidosis, prenatal diagnosis is available through amniocentesis. During amniocentesis, samples of fluid surrounding the fetus are removed. Fetal tissue samples may be obtained during a procedure known as chorionic villus sampling. Certain cells (fibroblasts) are cultured grown in the laboratory and evaluated for alpha-neuraminidase activity.
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Diagnosis of Sialidosis. A diagnosis of sialidosis is made based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. An examination of urine may reveal increased levels of oligosaccharides. A urine test is usually followed up by blood tests and a skin biopsy (surgical removal and microscopic study of skin tissue). These tests can reveal low levels of the enzyme alpha-neuraminidase in blood and skin tissue.For families with a previous history of sialidosis, prenatal diagnosis is available through amniocentesis. During amniocentesis, samples of fluid surrounding the fetus are removed. Fetal tissue samples may be obtained during a procedure known as chorionic villus sampling. Certain cells (fibroblasts) are cultured grown in the laboratory and evaluated for alpha-neuraminidase activity.
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Therapies of Sialidosis
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TreatmentThere is no specific therapy for sialidosis. Treatment is directed toward the specific symptoms that are apparent in each individual. Anti-seizure medications (anti-convulsants) may be used to treat myoclonic seizures, but are not always effective.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Therapies of Sialidosis. TreatmentThere is no specific therapy for sialidosis. Treatment is directed toward the specific symptoms that are apparent in each individual. Anti-seizure medications (anti-convulsants) may be used to treat myoclonic seizures, but are not always effective.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Overview of Sickle Cell Disease
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SummarySickle cell disease (SCD) is a rare blood disorder that is inherited in an autosomal recessive manner. It is characterized by the presence of sickle, or crescent-shaped, red blood cells (erythrocytes) in the bloodstream. These crescent-shaped cells are stiff and sticky and interact with other cells and the blood clotting system to block blood flow in the very tiny blood vessels (capillaries) of the peripheral blood system (blood vessels outside of the heart). This prevents the normal flow of nutrition and oxygen (as red blood cells are responsible for carrying oxygen throughout the body).Common symptoms associated with SCD include excruciating bone pain, chest pain, severe infections (primarily in children), low levels of circulating red blood cells (anemia) and yellowing of the skin (jaundice). The blocked blood flow can also cause severe organ damage including stroke. SCD has several recognized forms including sickle cell anemia, sickle cell hemoglobin C disease, and sickle cell / beta-thalassemia disease.
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Overview of Sickle Cell Disease. SummarySickle cell disease (SCD) is a rare blood disorder that is inherited in an autosomal recessive manner. It is characterized by the presence of sickle, or crescent-shaped, red blood cells (erythrocytes) in the bloodstream. These crescent-shaped cells are stiff and sticky and interact with other cells and the blood clotting system to block blood flow in the very tiny blood vessels (capillaries) of the peripheral blood system (blood vessels outside of the heart). This prevents the normal flow of nutrition and oxygen (as red blood cells are responsible for carrying oxygen throughout the body).Common symptoms associated with SCD include excruciating bone pain, chest pain, severe infections (primarily in children), low levels of circulating red blood cells (anemia) and yellowing of the skin (jaundice). The blocked blood flow can also cause severe organ damage including stroke. SCD has several recognized forms including sickle cell anemia, sickle cell hemoglobin C disease, and sickle cell / beta-thalassemia disease.
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Symptoms of Sickle Cell Disease
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Hemoglobin is an iron-rich protein contained in red blood cells and is responsible for carrying oxygen from the lungs to the rest of the body. In SCD, the symptoms stem from the abnormal hemoglobin in the red blood cells. The abnormal hemoglobin causes the red blood cells to be sickle-shaped which triggers a series of events leading to fragile red blood cells and blocking blood flow.The most common signs and symptoms of SCD are associated with low red blood cells (anemia) and pain. The most common symptom of anemia is feeling tired and weak (fatigue). Sickle cell pain episodes can occur suddenly and is typically in bones and the abdomen, but can occur almost anywhere. The pain can last for days to over a week (acute) or continue long-term (chronic). Damage can occur to most parts of the body including the brain, lung, kidneys, and joints. SCD can cause yellow eyes (jaundice) from the breakdown of blood. Signs in infants can include swollen and painful hands and/or feet (dactylitis), irritability, crying, and severe infections.In patients with SCD, the spleen can become enlarged (splenomegaly) as it traps red blood cells that should be in the bloodstream. The spleen functions to filter out abnormal red blood cells and fights some infections such as the bacteria that cause strep throat. Damage to the spleen leads to decreased ability to fight some typically mild infections that can become life-threatening in SCD.Acute chest syndrome can occur if an infection or sickled cells damages the lungs. This is a life-threatening complication of SCD. Sometimes people can’t tell they have it but other times people can have chest pain, difficulty breathing or fever. Additional complications of SCD include stroke, which can occur in children as young as 2 years. Boys and men with sickle cell disease may experience painful, prolonged erections (priapism) at any age.The signs and symptoms of SCD vary from patient to patient, and some patients have more mild symptoms while others may have more severe symptoms requiring hospitalization. SCD is present at birth; however, most infants do not show any signs until four months of age and many do not show signs until several years of age. The symptoms typically begin in the first three years of life. Sometimes the first suggestion of SCD is a painful swelling of an infant’s hands or feet (dactylitis). The extreme pain episodes are often triggered by something such as getting cold, becoming dehydrated, infection, over doing it, or trauma. Children with SCD may grow slowly and reach puberty later.As people with SCD age, other additional complications become more common. Pulmonary hypertension can develop due to damage to the small blood vessels and air sacs in the lungs. This can cause decreased ability to exercise, shortness of breath and tiredness. Leg sores that are often hard to heal can occur; damage to the retina can occur causing eye problems. Damage to the joints (avascular necrosis) and the loss of bone may cause pain in the joints when walking, standing and/or lifting. Kidney damage can occur and gallstones are often present.There are many forms of SCD. The most common severe form is S/S which some call sickle cell anemia. Some forms, like sickle beta-zero thalassemia are just as severe as the S/S form. Sickle beta-plus thalassemia and sickle cell hemoglobin C disease are usually less severe. Diagnosing exactly what form of SCD someone has is important and there is a lot of confusion about the different forms.
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Symptoms of Sickle Cell Disease. Hemoglobin is an iron-rich protein contained in red blood cells and is responsible for carrying oxygen from the lungs to the rest of the body. In SCD, the symptoms stem from the abnormal hemoglobin in the red blood cells. The abnormal hemoglobin causes the red blood cells to be sickle-shaped which triggers a series of events leading to fragile red blood cells and blocking blood flow.The most common signs and symptoms of SCD are associated with low red blood cells (anemia) and pain. The most common symptom of anemia is feeling tired and weak (fatigue). Sickle cell pain episodes can occur suddenly and is typically in bones and the abdomen, but can occur almost anywhere. The pain can last for days to over a week (acute) or continue long-term (chronic). Damage can occur to most parts of the body including the brain, lung, kidneys, and joints. SCD can cause yellow eyes (jaundice) from the breakdown of blood. Signs in infants can include swollen and painful hands and/or feet (dactylitis), irritability, crying, and severe infections.In patients with SCD, the spleen can become enlarged (splenomegaly) as it traps red blood cells that should be in the bloodstream. The spleen functions to filter out abnormal red blood cells and fights some infections such as the bacteria that cause strep throat. Damage to the spleen leads to decreased ability to fight some typically mild infections that can become life-threatening in SCD.Acute chest syndrome can occur if an infection or sickled cells damages the lungs. This is a life-threatening complication of SCD. Sometimes people can’t tell they have it but other times people can have chest pain, difficulty breathing or fever. Additional complications of SCD include stroke, which can occur in children as young as 2 years. Boys and men with sickle cell disease may experience painful, prolonged erections (priapism) at any age.The signs and symptoms of SCD vary from patient to patient, and some patients have more mild symptoms while others may have more severe symptoms requiring hospitalization. SCD is present at birth; however, most infants do not show any signs until four months of age and many do not show signs until several years of age. The symptoms typically begin in the first three years of life. Sometimes the first suggestion of SCD is a painful swelling of an infant’s hands or feet (dactylitis). The extreme pain episodes are often triggered by something such as getting cold, becoming dehydrated, infection, over doing it, or trauma. Children with SCD may grow slowly and reach puberty later.As people with SCD age, other additional complications become more common. Pulmonary hypertension can develop due to damage to the small blood vessels and air sacs in the lungs. This can cause decreased ability to exercise, shortness of breath and tiredness. Leg sores that are often hard to heal can occur; damage to the retina can occur causing eye problems. Damage to the joints (avascular necrosis) and the loss of bone may cause pain in the joints when walking, standing and/or lifting. Kidney damage can occur and gallstones are often present.There are many forms of SCD. The most common severe form is S/S which some call sickle cell anemia. Some forms, like sickle beta-zero thalassemia are just as severe as the S/S form. Sickle beta-plus thalassemia and sickle cell hemoglobin C disease are usually less severe. Diagnosing exactly what form of SCD someone has is important and there is a lot of confusion about the different forms.
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Causes of Sickle Cell Disease
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SCD is caused by mutations in the hemoglobin beta (HBB) gene and is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same altered 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 altered gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.In SCD this is more complicated. People who receive the sickle mutation from each parent (S/S) have the disease. Some people with SCD only get the sickle mutation from one parent, but have a different mutation from the other parent. This can lead to forms of SCD such as sickle beta- thalassemia and sickle cell hemoglobin C disease. Diagnosing exactly what form of SCD someone has is important and there is a lot of confusion about the different forms.People who inherit only one HBB gene mutation are said to have “sickle cell trait.” These people are generally symptom-free carriers who can pass the gene on to their offspring. Some people with sickle cell trait may have some medical complications and show some symptoms.
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Causes of Sickle Cell Disease. SCD is caused by mutations in the hemoglobin beta (HBB) gene and is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same altered 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 altered gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.In SCD this is more complicated. People who receive the sickle mutation from each parent (S/S) have the disease. Some people with SCD only get the sickle mutation from one parent, but have a different mutation from the other parent. This can lead to forms of SCD such as sickle beta- thalassemia and sickle cell hemoglobin C disease. Diagnosing exactly what form of SCD someone has is important and there is a lot of confusion about the different forms.People who inherit only one HBB gene mutation are said to have “sickle cell trait.” These people are generally symptom-free carriers who can pass the gene on to their offspring. Some people with sickle cell trait may have some medical complications and show some symptoms.
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Affects of Sickle Cell Disease
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The frequency of SCD varies from country to country. SCD affects 0.6 percent of the African American population in the United States (approximately 100,000 cases in the United States). It is also common in people of Hispanic decent, from India, Central America and the Arabian Peninsula, but can occur in people of any background. SCD affects approximately one in every 300 – 500 African American newborns. The sickle cell trait is present in approximately 40 percent of the general population in some areas of Africa. The incidence of sickle cell trait in Americans of African descent is 9 percent.Mutations in the HBB gene are common in people from African, Mediterranean, Middle Eastern, and Indian ancestry and in people from the Caribbean and parts of Central and South America, but can be found in people of any ethnicity.
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Affects of Sickle Cell Disease. The frequency of SCD varies from country to country. SCD affects 0.6 percent of the African American population in the United States (approximately 100,000 cases in the United States). It is also common in people of Hispanic decent, from India, Central America and the Arabian Peninsula, but can occur in people of any background. SCD affects approximately one in every 300 – 500 African American newborns. The sickle cell trait is present in approximately 40 percent of the general population in some areas of Africa. The incidence of sickle cell trait in Americans of African descent is 9 percent.Mutations in the HBB gene are common in people from African, Mediterranean, Middle Eastern, and Indian ancestry and in people from the Caribbean and parts of Central and South America, but can be found in people of any ethnicity.
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Related disorders of Sickle Cell Disease
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It has become easier to distinguish SCD from other disorders as for all children born in the US get tested for SCD at birth. In older patients and immigrants, SCD should be considered in those with anemia and / or recurrent pain, especially if they have family from the regions sickle cell is most common (for example Africa, and regions listed above). The diagnosis is easily confirmed with simple blood tests.
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Related disorders of Sickle Cell Disease. It has become easier to distinguish SCD from other disorders as for all children born in the US get tested for SCD at birth. In older patients and immigrants, SCD should be considered in those with anemia and / or recurrent pain, especially if they have family from the regions sickle cell is most common (for example Africa, and regions listed above). The diagnosis is easily confirmed with simple blood tests.
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Diagnosis of Sickle Cell Disease
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All newborns born in the US are tested for SCD by electrophoresis and or high pressure liquid chromatography. Molecular genetic testing for mutations in the HBB gene is also available.
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Diagnosis of Sickle Cell Disease. All newborns born in the US are tested for SCD by electrophoresis and or high pressure liquid chromatography. Molecular genetic testing for mutations in the HBB gene is also available.
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Therapies of Sickle Cell Disease
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Treatment
Prevention is the best treatment. Patient and family education, medicines such as hydroxycarbamide, avoiding triggers, early intervention, and testing to pick up developing complications early so they can be treated before they are severe can significantly improve outcomes.While very few patients with SCD have the opportunity to be cured, early referral of newborns to specialty centers can provide education and resources that help control symptoms and dramatically improve quality of life for patients. People with SCD should have regular medical checkups where education on preventing complications has a tremendous benefit on health. Teaching families about how to carefully monitor children for fevers while at home, giving low dose penicillin and immunizations, and assuring families have the information and ability to reach a hospital when ill dramatically decreases severe infections and death. Many simple lifestyle activities can be done to support health and minimize pain and other complications. These include remaining hydrated, not getting too hot or cold, getting exercise, deep breathing, not getting fatigued and avoiding trauma.It is important to try to avoid sickle cell pain as mentioned above. Once pain occurs, it is important to use many approaches to treat the severe pain in SCD, not just medications. Reversing triggers of pain is key, thus hydration, remaining warm, walking around and deep breathing are very important. Distraction can be a huge help, as are approaches such as massage, acupuncture, and hypnosis. Pain-relieving medications, such as non-steroidal anti-inflammatory agents and opiate analgesics may be administered during painful episodes.Blood transfusions can be used for many reasons such as very severe anemia, preparing for surgery, and to reduce the risk of, or treat stroke. In some people, surgery may be necessary because of damage to specific organs such as gall bladder surgery (cholecystectomy) to remove gallstones.Stem cell transplant can provide a cure for patients but the chance of success and potential risks vary depend on many factors.Hydroxycarbamide (hydroxyurea) has been approved by the Food and Drug Administration (FDA) for the treatment of SCD and is recommended for most patients with the S/S and sickle beta-zero thalassemia forms of SCD. It should be offered to children with these forms by 9 months of age. Hydroxyurea helps stimulate the body to make fetal hemoglobin, the type of hemoglobin that newborns have and lowers white blood cells that can contribute to slowing blood flow. As a result, hydroxycarbamide can decrease pain, improve the anemia, decrease hospitalizations and lung problems, and increase lifespan.In 2017, the FDA approved Endari (L-glutamine) for patients age five years and older with SCD to reduce severe complications associated with this condition. In 2019, the FDA approve two drugs for the treatment of SCD. Oxbryta (voxelotor) was approved to treat SCD in adults and pediatric patients 12 years of age and older and Adakveo (crizanlizumab-tmca) was approved as a treatment to reduce the frequency of vaso-occlusive crisis in SCD patients aged 16 years and older.Folic acid is used to assure the body can make enough red blood cells.Genetic counseling is recommended for affected individuals and their families.
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Therapies of Sickle Cell Disease. Treatment
Prevention is the best treatment. Patient and family education, medicines such as hydroxycarbamide, avoiding triggers, early intervention, and testing to pick up developing complications early so they can be treated before they are severe can significantly improve outcomes.While very few patients with SCD have the opportunity to be cured, early referral of newborns to specialty centers can provide education and resources that help control symptoms and dramatically improve quality of life for patients. People with SCD should have regular medical checkups where education on preventing complications has a tremendous benefit on health. Teaching families about how to carefully monitor children for fevers while at home, giving low dose penicillin and immunizations, and assuring families have the information and ability to reach a hospital when ill dramatically decreases severe infections and death. Many simple lifestyle activities can be done to support health and minimize pain and other complications. These include remaining hydrated, not getting too hot or cold, getting exercise, deep breathing, not getting fatigued and avoiding trauma.It is important to try to avoid sickle cell pain as mentioned above. Once pain occurs, it is important to use many approaches to treat the severe pain in SCD, not just medications. Reversing triggers of pain is key, thus hydration, remaining warm, walking around and deep breathing are very important. Distraction can be a huge help, as are approaches such as massage, acupuncture, and hypnosis. Pain-relieving medications, such as non-steroidal anti-inflammatory agents and opiate analgesics may be administered during painful episodes.Blood transfusions can be used for many reasons such as very severe anemia, preparing for surgery, and to reduce the risk of, or treat stroke. In some people, surgery may be necessary because of damage to specific organs such as gall bladder surgery (cholecystectomy) to remove gallstones.Stem cell transplant can provide a cure for patients but the chance of success and potential risks vary depend on many factors.Hydroxycarbamide (hydroxyurea) has been approved by the Food and Drug Administration (FDA) for the treatment of SCD and is recommended for most patients with the S/S and sickle beta-zero thalassemia forms of SCD. It should be offered to children with these forms by 9 months of age. Hydroxyurea helps stimulate the body to make fetal hemoglobin, the type of hemoglobin that newborns have and lowers white blood cells that can contribute to slowing blood flow. As a result, hydroxycarbamide can decrease pain, improve the anemia, decrease hospitalizations and lung problems, and increase lifespan.In 2017, the FDA approved Endari (L-glutamine) for patients age five years and older with SCD to reduce severe complications associated with this condition. In 2019, the FDA approve two drugs for the treatment of SCD. Oxbryta (voxelotor) was approved to treat SCD in adults and pediatric patients 12 years of age and older and Adakveo (crizanlizumab-tmca) was approved as a treatment to reduce the frequency of vaso-occlusive crisis in SCD patients aged 16 years and older.Folic acid is used to assure the body can make enough red blood cells.Genetic counseling is recommended for affected individuals and their families.
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Overview of Simian B Virus Infection
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Simian B Virus Infection is caused by a type of herpesvirus. It is an infectious disorder contracted chiefly by laboratory workers exposed to infected monkeys and/or simian tissue cultures. It is characterized by a viral invasion of the brain (Encephalitis) and the membranes (meninges) surrounding the brain. Occasionally, the infection affects the spinal cord structures as well (Encephalomyelitis). Neurological damage may result from this infection. Without treatment, some cases of Simian B Virus may be life- threatening.
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Overview of Simian B Virus Infection. Simian B Virus Infection is caused by a type of herpesvirus. It is an infectious disorder contracted chiefly by laboratory workers exposed to infected monkeys and/or simian tissue cultures. It is characterized by a viral invasion of the brain (Encephalitis) and the membranes (meninges) surrounding the brain. Occasionally, the infection affects the spinal cord structures as well (Encephalomyelitis). Neurological damage may result from this infection. Without treatment, some cases of Simian B Virus may be life- threatening.
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Symptoms of Simian B Virus Infection
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Simian B Virus Infection is characterized by fever, headache, vomiting, discomfort (malaise), and a stiff neck and back. These symptoms may be associated with neuromuscular dysfunction, respiratory difficulties, vision problems, cranial nerve abnormalities, alteration of consciousness, personality changes, seizures and/or partial paralysis (paresis). Some patients may go into a coma.
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Symptoms of Simian B Virus Infection. Simian B Virus Infection is characterized by fever, headache, vomiting, discomfort (malaise), and a stiff neck and back. These symptoms may be associated with neuromuscular dysfunction, respiratory difficulties, vision problems, cranial nerve abnormalities, alteration of consciousness, personality changes, seizures and/or partial paralysis (paresis). Some patients may go into a coma.
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Causes of Simian B Virus Infection
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Simian B Virus Infection is caused by herpesvirus simiae (also known as B virus), a type of herpesvirus that is highly prevalent (i.e., enzootic) among macaque monkeys, i.e., certain Asiatic monkeys belonging to the “Macaca” genus. According to some reports, up to 80 or 90 percent of adult macaques may be infected with the virus.In humans, Simian B Virus Infection may result from exposure to contaminated saliva from infected monkeys (e.g., from bites or scratches) or to simian tissue cultures of the virus, usually in laboratory settings. In addition, there has been at least one instance in which person-to-person transmission occurred.
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Causes of Simian B Virus Infection. Simian B Virus Infection is caused by herpesvirus simiae (also known as B virus), a type of herpesvirus that is highly prevalent (i.e., enzootic) among macaque monkeys, i.e., certain Asiatic monkeys belonging to the “Macaca” genus. According to some reports, up to 80 or 90 percent of adult macaques may be infected with the virus.In humans, Simian B Virus Infection may result from exposure to contaminated saliva from infected monkeys (e.g., from bites or scratches) or to simian tissue cultures of the virus, usually in laboratory settings. In addition, there has been at least one instance in which person-to-person transmission occurred.
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Affects of Simian B Virus Infection
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According to reports in the medical literature, symptoms associated with Simian B Virus Infection typically occur within approximately two to five weeks after initial exposure. Simian B Virus Infection usually occurs in an occupational setting in which employees have been bitten or scratched by infected monkeys or exposed to virus-infected simian tissue cultures. The disease was originally reported in a monkey handler in 1932. Through 1973, approximately 17 additional cases were reported in the medical literature. In addition, in 1987, four more individuals were affected by the disease, including the first documented case in which human-to-human disease transmission occurred. Fewer than a total of 40 cases of Simian B Virus Infection have been reported in humans to date. Researchers suggest, however, that the true frequency of Simian B Virus Infection may be difficult to assess, since it is possible that exposure to the virus may result in mild or no apparent symptoms (asymptomatic infection) in some cases.Since 1975, United States public health regulations have prohibited the importation of primates as pets. However, according to researchers at the Centers for Disease Control and Prevention (CDC), there have been a number of incidents in nonoccupational settings in which individuals were exposed to the saliva of pet macaques (e.g., due to bites or scratches). According to one published CDC report, investigators examined seven nonoccupational exposures involving 24 individuals and eight monkeys. One exposed family had flu-like symptoms and another individual developed symptoms at the wound site suggesting infection. The researchers stress that infection must be assumed as a potential risk of macaque bite or scratch wounds, making macaques unacceptable as pets.
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Affects of Simian B Virus Infection. According to reports in the medical literature, symptoms associated with Simian B Virus Infection typically occur within approximately two to five weeks after initial exposure. Simian B Virus Infection usually occurs in an occupational setting in which employees have been bitten or scratched by infected monkeys or exposed to virus-infected simian tissue cultures. The disease was originally reported in a monkey handler in 1932. Through 1973, approximately 17 additional cases were reported in the medical literature. In addition, in 1987, four more individuals were affected by the disease, including the first documented case in which human-to-human disease transmission occurred. Fewer than a total of 40 cases of Simian B Virus Infection have been reported in humans to date. Researchers suggest, however, that the true frequency of Simian B Virus Infection may be difficult to assess, since it is possible that exposure to the virus may result in mild or no apparent symptoms (asymptomatic infection) in some cases.Since 1975, United States public health regulations have prohibited the importation of primates as pets. However, according to researchers at the Centers for Disease Control and Prevention (CDC), there have been a number of incidents in nonoccupational settings in which individuals were exposed to the saliva of pet macaques (e.g., due to bites or scratches). According to one published CDC report, investigators examined seven nonoccupational exposures involving 24 individuals and eight monkeys. One exposed family had flu-like symptoms and another individual developed symptoms at the wound site suggesting infection. The researchers stress that infection must be assumed as a potential risk of macaque bite or scratch wounds, making macaques unacceptable as pets.
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Related disorders of Simian B Virus Infection
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Symptoms of the following disorders can be similar to those of Simian B Virus. Comparisons may be useful for a differential diagnosis:Acute Disseminated Encephalomyelitis is an infection of the nervous system characterized by headache, irritability, vomiting, drowsiness, light- sensitivity, difficulty in swallowing, lockjaw, incontinence, and diminished or exaggerated skin sensations. This disorder can be caused by viral infections acquired from sources other than Simian B Virus infected monkeys. It may be an allergic or toxic response of the nervous system to invading organisms such as bacteria or viruses. Neurological damage and intellectual impairment can follow an attack of this condition. (For more information on this disorder, choose “Encephalomyelitis” as your search term in the Rare Disease Database.)
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Related disorders of Simian B Virus Infection. Symptoms of the following disorders can be similar to those of Simian B Virus. Comparisons may be useful for a differential diagnosis:Acute Disseminated Encephalomyelitis is an infection of the nervous system characterized by headache, irritability, vomiting, drowsiness, light- sensitivity, difficulty in swallowing, lockjaw, incontinence, and diminished or exaggerated skin sensations. This disorder can be caused by viral infections acquired from sources other than Simian B Virus infected monkeys. It may be an allergic or toxic response of the nervous system to invading organisms such as bacteria or viruses. Neurological damage and intellectual impairment can follow an attack of this condition. (For more information on this disorder, choose “Encephalomyelitis” as your search term in the Rare Disease Database.)
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Diagnosis of Simian B Virus Infection
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Diagnosis of Simian B Virus Infection.
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Therapies of Simian B Virus Infection
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The Centers for Disease Control and Prevention (CDC) has published a series of guidelines for the prevention of Simian B Virus Infection among monkey handlers. Such guidelines include receiving training in appropriate methods of restraint and the use of proper protective clothing and equipment when handling potentially infected monkeys. The CDC and the National Institutes of Health (NIH) have also published guidelines concerning appropriate measures for working with the B virus in a laboratory setting. For further information, please contact the CDC and/or the NIH (listed in the "References" section of this report below).According to reports in the literature, in some affected individuals, the antiviral drug acyclovir may be effective in treating Simian B Virus Infection. In some cases, therapy may include intravenous infusion of ganciclovir, an antiviral medication structurally related to acyclovir.Other treatment for Simian B Virus Infection is symptomatic and supportive.
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Therapies of Simian B Virus Infection. The Centers for Disease Control and Prevention (CDC) has published a series of guidelines for the prevention of Simian B Virus Infection among monkey handlers. Such guidelines include receiving training in appropriate methods of restraint and the use of proper protective clothing and equipment when handling potentially infected monkeys. The CDC and the National Institutes of Health (NIH) have also published guidelines concerning appropriate measures for working with the B virus in a laboratory setting. For further information, please contact the CDC and/or the NIH (listed in the "References" section of this report below).According to reports in the literature, in some affected individuals, the antiviral drug acyclovir may be effective in treating Simian B Virus Infection. In some cases, therapy may include intravenous infusion of ganciclovir, an antiviral medication structurally related to acyclovir.Other treatment for Simian B Virus Infection is symptomatic and supportive.
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Overview of Simple Pulmonary Eosinophilia
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SummarySimple pulmonary eosinophilia (SPE), also known as Loeffler syndrome, is a rare, temporary (transient) respiratory disorder characterized by the accumulation of eosinophils in the lungs (pulmonary eosinophilia). Eosinophils are a type of white blood cell and are part of the immune system. They are usually produced in response to allergens, inflammation or infection and are particularly active in the respiratory tract. Most cases of SPE are believed to be due to an allergic reaction to drugs or infection (mainly parasitic ones). SPE usually ranges in severity from individuals who do not develop any symptoms to individuals who develop mild respiratory symptoms. In rare cases, more significant complications can occur. Generally, no specific therapy is required as symptoms usually go away spontaneously without treatment.IntroductionSimple pulmonary eosinophilia was first described in the medical literature in 1932. It is classified as a form of eosinophilic lung disease. SPE is considered a benign, self-limiting disorder.
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Overview of Simple Pulmonary Eosinophilia. SummarySimple pulmonary eosinophilia (SPE), also known as Loeffler syndrome, is a rare, temporary (transient) respiratory disorder characterized by the accumulation of eosinophils in the lungs (pulmonary eosinophilia). Eosinophils are a type of white blood cell and are part of the immune system. They are usually produced in response to allergens, inflammation or infection and are particularly active in the respiratory tract. Most cases of SPE are believed to be due to an allergic reaction to drugs or infection (mainly parasitic ones). SPE usually ranges in severity from individuals who do not develop any symptoms to individuals who develop mild respiratory symptoms. In rare cases, more significant complications can occur. Generally, no specific therapy is required as symptoms usually go away spontaneously without treatment.IntroductionSimple pulmonary eosinophilia was first described in the medical literature in 1932. It is classified as a form of eosinophilic lung disease. SPE is considered a benign, self-limiting disorder.
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Symptoms of Simple Pulmonary Eosinophilia
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SPE usually presents as a mild lung disorder characterized by a dry, unproductive cough, wheezing and a slight fever. Some affected individuals may cough up a mixture of saliva and mucus (sputum). Symptoms usually resolve on their own without treatment (spontaneous resolution) within two weeks to a month. In some cases, symptoms can persist for months, especially in the setting of antigen re-exposure.Additional symptoms can occur including chest pain, wheezing, shortness of breath (dyspnea), and a rapid breathing rate. Some individuals may complain of a general feeling of poor health (malaise). Inflammation of the mucous membranes of the nose (rhinitis), unintended weight loss and night sweats have also been reported.Some individuals with SPE develop acute eosinophilic pneumonia (AEP). AEP is a rare, serious lung disorder that can quickly progress to cause acute respiratory failure. (For more information on AEP, see the related disorders section below).
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Symptoms of Simple Pulmonary Eosinophilia. SPE usually presents as a mild lung disorder characterized by a dry, unproductive cough, wheezing and a slight fever. Some affected individuals may cough up a mixture of saliva and mucus (sputum). Symptoms usually resolve on their own without treatment (spontaneous resolution) within two weeks to a month. In some cases, symptoms can persist for months, especially in the setting of antigen re-exposure.Additional symptoms can occur including chest pain, wheezing, shortness of breath (dyspnea), and a rapid breathing rate. Some individuals may complain of a general feeling of poor health (malaise). Inflammation of the mucous membranes of the nose (rhinitis), unintended weight loss and night sweats have also been reported.Some individuals with SPE develop acute eosinophilic pneumonia (AEP). AEP is a rare, serious lung disorder that can quickly progress to cause acute respiratory failure. (For more information on AEP, see the related disorders section below).
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Causes of Simple Pulmonary Eosinophilia
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Generally, SPE is caused by an allergic reaction. A variety of factors including parasitic infection, exposure to certain drugs or exposure to certain fungi have been linked to SPE. In some cases of SPE, the triggering event or cause of SPE is unknown (idiopathic). The exact reason why there is an overproduction and accumulation of eosinophils in the lungs in individuals with SPE is not fully understood.The passage of parasitic larvae through the lungs causes most cases, which results in an allergic reaction. Parasitic worms (helminths) such as nematodes are the most common parasitic cause associated with SPE. The term nematode is a classification (i.e., phylum) of worms characterized by long, round, generally smooth bodies. Nematodes that have been linked to SPE include hookworms and Ascaris lumbricoides, a type of roundworm.Drugs that have been linked to cases of SPE include nonsteroidal anti-inflammatory drugs (NSAIDs), certain antibiotics, anti-microbials, and anti-seizure medications (anticonvulsants).Some cases of SPE have been caused by exposure to certain fungi such as Aspergillus fumigatus.
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Causes of Simple Pulmonary Eosinophilia. Generally, SPE is caused by an allergic reaction. A variety of factors including parasitic infection, exposure to certain drugs or exposure to certain fungi have been linked to SPE. In some cases of SPE, the triggering event or cause of SPE is unknown (idiopathic). The exact reason why there is an overproduction and accumulation of eosinophils in the lungs in individuals with SPE is not fully understood.The passage of parasitic larvae through the lungs causes most cases, which results in an allergic reaction. Parasitic worms (helminths) such as nematodes are the most common parasitic cause associated with SPE. The term nematode is a classification (i.e., phylum) of worms characterized by long, round, generally smooth bodies. Nematodes that have been linked to SPE include hookworms and Ascaris lumbricoides, a type of roundworm.Drugs that have been linked to cases of SPE include nonsteroidal anti-inflammatory drugs (NSAIDs), certain antibiotics, anti-microbials, and anti-seizure medications (anticonvulsants).Some cases of SPE have been caused by exposure to certain fungi such as Aspergillus fumigatus.
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Affects of Simple Pulmonary Eosinophilia
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SPE affects males and females in equal numbers. The exact incidence and prevalence of SPE in the general population is unknown. It is the most common form of eosinophilic lung disease. SPE can affect individuals of any age.
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Affects of Simple Pulmonary Eosinophilia. SPE affects males and females in equal numbers. The exact incidence and prevalence of SPE in the general population is unknown. It is the most common form of eosinophilic lung disease. SPE can affect individuals of any age.
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Related disorders of Simple Pulmonary Eosinophilia
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Symptoms of the following disorders can be similar to those of SPE. Comparisons may be useful for a differential diagnosis.Eosinophilic lung diseases are a broad group of disorders. These diseases can be broken down into types without a known cause (idiopathic) and those with a known cause. Eosinophilic lung diseases without a known cause include AEP, chronic eosinophilic pneumonia (CEP), and idiopathic hypereosinophilic syndrome. Known causes of eosinophilic lung disease include allergic bronchopulmonary aspergillosis, exposure to parasitic infections, drugs, or toxic substances and systemic disorders such as Churg-Strauss syndrome and hypereosinophilic syndorme. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Related disorders of Simple Pulmonary Eosinophilia. Symptoms of the following disorders can be similar to those of SPE. Comparisons may be useful for a differential diagnosis.Eosinophilic lung diseases are a broad group of disorders. These diseases can be broken down into types without a known cause (idiopathic) and those with a known cause. Eosinophilic lung diseases without a known cause include AEP, chronic eosinophilic pneumonia (CEP), and idiopathic hypereosinophilic syndrome. Known causes of eosinophilic lung disease include allergic bronchopulmonary aspergillosis, exposure to parasitic infections, drugs, or toxic substances and systemic disorders such as Churg-Strauss syndrome and hypereosinophilic syndorme. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Diagnosis of Simple Pulmonary Eosinophilia
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A diagnosis of SPE is based upon identification of characteristic symptoms (e.g., eosinophilic pneumonia), a detailed patient history, a thorough clinical evaluation, the absence of other known causes of eosinophilic lung disease, and a variety of specialized tests. A physical examination may reveal wheezing and/or a rattling sound in the lungs (rales). Distinguishing SPE from other, more severe forms of pulmonary eosinophilia is especially important when obtaining a diagnosis.Clinical Testing and Work-Up
Imaging techniques may be used to help confirm a diagnosis of SPE including chest x-ray or computerized tomography (CT) scanning. Chest x-rays in individuals with SPE generally show white patches or shadows (infiltrates) in the lungs. These infiltrates may disappear, but can reappear in different areas of the lungs. A CT scan may reveal hazy areas (ground-glass opacities) that are not seen on traditional x-rays. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of tissue structures such as the lungs. A CT scan can also show airspace consolidation, in which the tiny air sacs of the lungs (alveolar) become abnormally filled (as with eosinophils).A procedure known as bronchoalveolar lavage (BAL) may also be used to help obtain a diagnosis of SPE. During BAL, a narrow tube (bronchoscope) is slid down the windpipe into the lungs and a sterile solution is passed through the tube washing out (lavaging) cells. This fluid is collected and then the tube is removed, allowing the cells to be studied. BAL in individuals with SPE reveals abnormally high levels of eosinophils.Blood tests may reveal elevated levels of eosinophils (i.e., eosinophilia) and/or serum immunoglobulin E (IgE) and may coincide with pulmonary manifestations. A stool examination may reveal the presence of parasites. Analysis of sputum or fluid obtained from pumping the stomach (gastric lavage) may reveal parasitic larvae.Additional tests may be performed to rule out other causes of pulmonary eosinophilia.
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Diagnosis of Simple Pulmonary Eosinophilia. A diagnosis of SPE is based upon identification of characteristic symptoms (e.g., eosinophilic pneumonia), a detailed patient history, a thorough clinical evaluation, the absence of other known causes of eosinophilic lung disease, and a variety of specialized tests. A physical examination may reveal wheezing and/or a rattling sound in the lungs (rales). Distinguishing SPE from other, more severe forms of pulmonary eosinophilia is especially important when obtaining a diagnosis.Clinical Testing and Work-Up
Imaging techniques may be used to help confirm a diagnosis of SPE including chest x-ray or computerized tomography (CT) scanning. Chest x-rays in individuals with SPE generally show white patches or shadows (infiltrates) in the lungs. These infiltrates may disappear, but can reappear in different areas of the lungs. A CT scan may reveal hazy areas (ground-glass opacities) that are not seen on traditional x-rays. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of tissue structures such as the lungs. A CT scan can also show airspace consolidation, in which the tiny air sacs of the lungs (alveolar) become abnormally filled (as with eosinophils).A procedure known as bronchoalveolar lavage (BAL) may also be used to help obtain a diagnosis of SPE. During BAL, a narrow tube (bronchoscope) is slid down the windpipe into the lungs and a sterile solution is passed through the tube washing out (lavaging) cells. This fluid is collected and then the tube is removed, allowing the cells to be studied. BAL in individuals with SPE reveals abnormally high levels of eosinophils.Blood tests may reveal elevated levels of eosinophils (i.e., eosinophilia) and/or serum immunoglobulin E (IgE) and may coincide with pulmonary manifestations. A stool examination may reveal the presence of parasites. Analysis of sputum or fluid obtained from pumping the stomach (gastric lavage) may reveal parasitic larvae.Additional tests may be performed to rule out other causes of pulmonary eosinophilia.
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Therapies of Simple Pulmonary Eosinophilia
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TreatmentIn most patients, no treatment is required and SPE goes away on its own (spontaneous remission). Cases due to active parasitic infection should be treated with appropriate anti-parasitic medications. Drug-induced cases should be treated by stopping the suspected offending drug. Respiratory symptoms such as wheeze and cough may be managed with inhaled bronchodilators. In rare cases, after active infection has been ruled out, corticosteroid therapy may be required and is generally effective.
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Therapies of Simple Pulmonary Eosinophilia. TreatmentIn most patients, no treatment is required and SPE goes away on its own (spontaneous remission). Cases due to active parasitic infection should be treated with appropriate anti-parasitic medications. Drug-induced cases should be treated by stopping the suspected offending drug. Respiratory symptoms such as wheeze and cough may be managed with inhaled bronchodilators. In rare cases, after active infection has been ruled out, corticosteroid therapy may be required and is generally effective.
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Overview of Simpson-Golabi-Behmel Syndrome
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Summary Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic condition that mostly affects males. In SGBS type 1, one of the main features is overgrowth, which is when an individual is larger than expected. This can be seen in overgrowth before birth, where the unborn baby is unusually large, and in overgrowth after birth, where a baby is unusually large. Other physical features that are commonly seen in individuals with SGBS are specific facial features like large forehead, nose, lips, and tongue. Some people with SGBS have an opening in the roof of their mouth (cleft palate). They can also have an opening in the upper lip (cleft lip). People with SGBS can have differences in other parts of their bodies too. Some of the differences that are more commonly seen include having an extra nipple, problems with their bones, and a bulge near the belly button called an umbilical hernia. Having SGBS can also mean that a person has a higher chance of having a heart problem. People with SGBS normally have some of these features, but not all of them. People with SGBS have differences and similarities, and some people have a more serious version of the condition than others. Some people with SBGS have intellectual disability, with a wide range of severity. About 10% of people with SGBS develop specific types of tumors as children. SGBS type 2 is the more serious form of the condition, and it can be life threatening in babies who are affected. Although there is no specific treatment or cure, there are ways to manage the symptoms, or specific features a person has. A team of doctors and other health care providers is often needed to determine the treatment options based on each person’s symptoms.IntroductionThere are many different names for Simpson-Golabi-Behmel syndrome. Some of these names have words that relate to symptoms of the condition and some contain names of doctors who have worked with patients with this condition. The name that is currently the most commonly used is Simpson-Golabi-Behmel syndrome, which combines the names of three doctors. Dr. Simpson published a paper on the condition in 1975, and Dr. Golabi and Dr. Behmel published papers on the condition in 1984.
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Overview of Simpson-Golabi-Behmel Syndrome. Summary Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic condition that mostly affects males. In SGBS type 1, one of the main features is overgrowth, which is when an individual is larger than expected. This can be seen in overgrowth before birth, where the unborn baby is unusually large, and in overgrowth after birth, where a baby is unusually large. Other physical features that are commonly seen in individuals with SGBS are specific facial features like large forehead, nose, lips, and tongue. Some people with SGBS have an opening in the roof of their mouth (cleft palate). They can also have an opening in the upper lip (cleft lip). People with SGBS can have differences in other parts of their bodies too. Some of the differences that are more commonly seen include having an extra nipple, problems with their bones, and a bulge near the belly button called an umbilical hernia. Having SGBS can also mean that a person has a higher chance of having a heart problem. People with SGBS normally have some of these features, but not all of them. People with SGBS have differences and similarities, and some people have a more serious version of the condition than others. Some people with SBGS have intellectual disability, with a wide range of severity. About 10% of people with SGBS develop specific types of tumors as children. SGBS type 2 is the more serious form of the condition, and it can be life threatening in babies who are affected. Although there is no specific treatment or cure, there are ways to manage the symptoms, or specific features a person has. A team of doctors and other health care providers is often needed to determine the treatment options based on each person’s symptoms.IntroductionThere are many different names for Simpson-Golabi-Behmel syndrome. Some of these names have words that relate to symptoms of the condition and some contain names of doctors who have worked with patients with this condition. The name that is currently the most commonly used is Simpson-Golabi-Behmel syndrome, which combines the names of three doctors. Dr. Simpson published a paper on the condition in 1975, and Dr. Golabi and Dr. Behmel published papers on the condition in 1984.
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Symptoms of Simpson-Golabi-Behmel Syndrome
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Simpson-Golabi-Behmel Syndrome Type 1 Many different parts of the body can be affected when a person has SGBS. Not every person with SGBS has the same symptoms, and none have all of these symptoms.OverallHeadCentral Nervous SystemSpeech and LanguageHeartAbdomenGenitalsSkeletalTumorsPregnancySimpson-Golabi-Behmel Syndrome Type 2SGBS type 2 is more serious and rarer than type 1. Boys with SGBS type 2 usually die a few months after birth. Most affected boys are born with extra fluid in multiple parts of the body (hydrops fetalis) and they also can have problems with their bones, distinct facial features, issues with organs and other medical problems.
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Symptoms of Simpson-Golabi-Behmel Syndrome. Simpson-Golabi-Behmel Syndrome Type 1 Many different parts of the body can be affected when a person has SGBS. Not every person with SGBS has the same symptoms, and none have all of these symptoms.OverallHeadCentral Nervous SystemSpeech and LanguageHeartAbdomenGenitalsSkeletalTumorsPregnancySimpson-Golabi-Behmel Syndrome Type 2SGBS type 2 is more serious and rarer than type 1. Boys with SGBS type 2 usually die a few months after birth. Most affected boys are born with extra fluid in multiple parts of the body (hydrops fetalis) and they also can have problems with their bones, distinct facial features, issues with organs and other medical problems.
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Causes of Simpson-Golabi-Behmel Syndrome
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SGBS type 1 is caused by harmful changes (mutations) in the genes GPC3 and GPC4, located on the X chromosome. SGBS type 2 is caused by mutations in the genes OFD1 and PIGA, also located on the X chromosome. They are genetic disorders that are inherited in a recessive X-linked pattern. The gene glypican 3 (GPC3) contributes to the control of growth and changes in this gene may lead to overgrowth. It is thought that organs of the body such as the heart and liver reach normal size when the GPC3 protein is available in large enough quantities. Concentration is sufficient when GPC3, the growth inhibiting factor, balances the growth promoting factors, such as insulin-like growth factor 2, IGF2. SGBS is inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by a mutation in a gene on the X chromosome. Mutations are changes in the way that genes, the body’s instructions, are written that cause the genes to not work in the way they should. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Some female carriers of SGBS have symptoms, but if they do their symptoms are normally mild. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
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Causes of Simpson-Golabi-Behmel Syndrome. SGBS type 1 is caused by harmful changes (mutations) in the genes GPC3 and GPC4, located on the X chromosome. SGBS type 2 is caused by mutations in the genes OFD1 and PIGA, also located on the X chromosome. They are genetic disorders that are inherited in a recessive X-linked pattern. The gene glypican 3 (GPC3) contributes to the control of growth and changes in this gene may lead to overgrowth. It is thought that organs of the body such as the heart and liver reach normal size when the GPC3 protein is available in large enough quantities. Concentration is sufficient when GPC3, the growth inhibiting factor, balances the growth promoting factors, such as insulin-like growth factor 2, IGF2. SGBS is inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by a mutation in a gene on the X chromosome. Mutations are changes in the way that genes, the body’s instructions, are written that cause the genes to not work in the way they should. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Some female carriers of SGBS have symptoms, but if they do their symptoms are normally mild. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
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Affects of Simpson-Golabi-Behmel Syndrome
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SGBS is present from birth (congenital) and can be diagnosed in a baby, even though some of the features might not appear until a child is older. All males who have a mutation in one of the genes for SGBS will have the condition. It is not known what percentage of carrier females have symptoms. As of 2014, there were 250 known cases of SGBS type 1. As of 2019, there have been 8 symptomatic female carriers reported.
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Affects of Simpson-Golabi-Behmel Syndrome. SGBS is present from birth (congenital) and can be diagnosed in a baby, even though some of the features might not appear until a child is older. All males who have a mutation in one of the genes for SGBS will have the condition. It is not known what percentage of carrier females have symptoms. As of 2014, there were 250 known cases of SGBS type 1. As of 2019, there have been 8 symptomatic female carriers reported.
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Related disorders of Simpson-Golabi-Behmel Syndrome
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Symptoms of the following disorders can be similar to those of SGBS. Comparisons may be useful for a differential diagnosis: Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder. There are a broad range of symptoms that can vary in location and severity. Features may include above average weight and length at birth and/or increased growth after birth (postnatally); an unusually large tongue (macroglossia); enlargement of certain abdominal organs (visceromegaly); and/or abdominal wall defects. People with BWS may also have low blood sugar levels at birth (neonatal hypoglycemia); advanced bone age, particularly up to age four, and/or an increased risk of developing certain childhood cancers. (For more information on this disorder, choose “BWS” as your search term in the Rare Disease Database.) Sotos syndrome is a rare genetic disorder characterized by excessive growth that occurs prior to and after birth (prenatally and postnatally). Newborns typically show advanced bone growth, abnormally large hands and/or feet, and unique facial features. These facial features may include an unusually large head (macrocephaly) that may appear elongated (dolichocephalic) with a large forehead (frontal bossing); widely-spaced eyes (ocular hypertelorism); downwardly slanting eyelid folds (palpebral fissures), a highly-arched roof of the mouth (palate), jutting of the lower jaw (prognathism); and/or a pointed chin. Most people with Sotos syndrome have mutations of the NSD1 gene. The mutation usually occurs by chance for no apparent reason (sporadically). When the mutation is already present, it is inherited as an autosomal dominant trait. Affected infants and children may also have delays in reaching developmental milestones (e.g., sitting, crawling, walking), delays in the coordination of muscular and mental activity and delayed language skills. (For more information on this disorder, choose “Sotos” as your search term in the Rare Disease Database.) Weaver syndrome, also known as Weaver-Smith syndrome, is an extremely rare disorder characterized by accelerated growth. Affected individuals have a particular facial appearance that is similar to Sotos syndrome in that a high broad forehead is often present, but the face is usually round in shape with widely spaced eyes (ocular hypertelorism) and an abnormally small jaw. Children with Weaver syndrome often have increased muscle tone (hypertonia) and joint problems. Weaver syndrome is due to mutations in the EZH2 gene. (For more information on this disorder, choose “Weaver” as your search term in the Rare Disease Database.) Craniometaphyseal dysplasia is a rare genetic disorder characterized by unique facial features that include a wide nasal bridge, widely spaced eyes (hypertelorism), overgrowth of the bone over the eyes, a small jawbone, and incomplete development of the sinuses. Multiple abnormalities of the teeth and bones may also be present. Intelligence is usually normal. (For more information on this disorder, choose “craniometaphyseal dysplasia” as your search term in the Rare Disease Database.) Oral-facial-digital syndrome is a rare genetic disorder in which there have been four types identified. Symptoms common to all types include periods of muscle abnormalities, split (cleft) tongue, splits in the jaw, midline cleft lip, overgrowth of the membrane that supports the tongue (frenulum), a broad based nose, vertical folds of the skin covering the inner angle of the eyelids (epicanthic folds), more than the normal number of fingers and/or toes, shorter than normal fingers and/or toes, and more than the normal number of divisions between skull sections. (For more information on this disorder, choose “oral-facial-digital” as your search term in the Rare Disease Database.) Otopalatodigital syndrome (OPD) types I and II are rare genetic disorders which are usually found in males. Females may be mildly affected with some of the symptoms. Some of the characteristics of both types I and II may be cleft palate, a downward slant of the opening between the upper and lower eyelids, hearing loss, and/or short fingers and toes. Symptoms of OPD I can include dislocation of the head of one of the bones of the forearm (radius), mild dwarfism, and/or underdeveloped bones of the face. Symptoms of OPD II can include a small head, fingers that are bent and overlap, or curved long bones of the forearm and legs. (For more information on this disorder, choose “otopalatodigital syndrome” as your search term in the Rare Disease Database.) Larsen syndrome is a multi-system genetic disorder that is present at birth. It is characterized by multiple bone dislocations and differences, an extremely high arch of the foot, non-tapering cylindrically shaped fingers, and an unusual facial appearance. (For more information on this disorder, choose “Larsen” as your search term in the Rare Disease Database.)
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Related disorders of Simpson-Golabi-Behmel Syndrome. Symptoms of the following disorders can be similar to those of SGBS. Comparisons may be useful for a differential diagnosis: Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder. There are a broad range of symptoms that can vary in location and severity. Features may include above average weight and length at birth and/or increased growth after birth (postnatally); an unusually large tongue (macroglossia); enlargement of certain abdominal organs (visceromegaly); and/or abdominal wall defects. People with BWS may also have low blood sugar levels at birth (neonatal hypoglycemia); advanced bone age, particularly up to age four, and/or an increased risk of developing certain childhood cancers. (For more information on this disorder, choose “BWS” as your search term in the Rare Disease Database.) Sotos syndrome is a rare genetic disorder characterized by excessive growth that occurs prior to and after birth (prenatally and postnatally). Newborns typically show advanced bone growth, abnormally large hands and/or feet, and unique facial features. These facial features may include an unusually large head (macrocephaly) that may appear elongated (dolichocephalic) with a large forehead (frontal bossing); widely-spaced eyes (ocular hypertelorism); downwardly slanting eyelid folds (palpebral fissures), a highly-arched roof of the mouth (palate), jutting of the lower jaw (prognathism); and/or a pointed chin. Most people with Sotos syndrome have mutations of the NSD1 gene. The mutation usually occurs by chance for no apparent reason (sporadically). When the mutation is already present, it is inherited as an autosomal dominant trait. Affected infants and children may also have delays in reaching developmental milestones (e.g., sitting, crawling, walking), delays in the coordination of muscular and mental activity and delayed language skills. (For more information on this disorder, choose “Sotos” as your search term in the Rare Disease Database.) Weaver syndrome, also known as Weaver-Smith syndrome, is an extremely rare disorder characterized by accelerated growth. Affected individuals have a particular facial appearance that is similar to Sotos syndrome in that a high broad forehead is often present, but the face is usually round in shape with widely spaced eyes (ocular hypertelorism) and an abnormally small jaw. Children with Weaver syndrome often have increased muscle tone (hypertonia) and joint problems. Weaver syndrome is due to mutations in the EZH2 gene. (For more information on this disorder, choose “Weaver” as your search term in the Rare Disease Database.) Craniometaphyseal dysplasia is a rare genetic disorder characterized by unique facial features that include a wide nasal bridge, widely spaced eyes (hypertelorism), overgrowth of the bone over the eyes, a small jawbone, and incomplete development of the sinuses. Multiple abnormalities of the teeth and bones may also be present. Intelligence is usually normal. (For more information on this disorder, choose “craniometaphyseal dysplasia” as your search term in the Rare Disease Database.) Oral-facial-digital syndrome is a rare genetic disorder in which there have been four types identified. Symptoms common to all types include periods of muscle abnormalities, split (cleft) tongue, splits in the jaw, midline cleft lip, overgrowth of the membrane that supports the tongue (frenulum), a broad based nose, vertical folds of the skin covering the inner angle of the eyelids (epicanthic folds), more than the normal number of fingers and/or toes, shorter than normal fingers and/or toes, and more than the normal number of divisions between skull sections. (For more information on this disorder, choose “oral-facial-digital” as your search term in the Rare Disease Database.) Otopalatodigital syndrome (OPD) types I and II are rare genetic disorders which are usually found in males. Females may be mildly affected with some of the symptoms. Some of the characteristics of both types I and II may be cleft palate, a downward slant of the opening between the upper and lower eyelids, hearing loss, and/or short fingers and toes. Symptoms of OPD I can include dislocation of the head of one of the bones of the forearm (radius), mild dwarfism, and/or underdeveloped bones of the face. Symptoms of OPD II can include a small head, fingers that are bent and overlap, or curved long bones of the forearm and legs. (For more information on this disorder, choose “otopalatodigital syndrome” as your search term in the Rare Disease Database.) Larsen syndrome is a multi-system genetic disorder that is present at birth. It is characterized by multiple bone dislocations and differences, an extremely high arch of the foot, non-tapering cylindrically shaped fingers, and an unusual facial appearance. (For more information on this disorder, choose “Larsen” as your search term in the Rare Disease Database.)
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Diagnosis of Simpson-Golabi-Behmel Syndrome
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Diagnosis of SGBS type 1 is made based on physical features of the patient, family history and genetic testing. There are no official criteria that are used to diagnose the condition. The main physical features are the different types of overgrowth (large body, large head, large fetus, large baby), the specific facial features, abnormalities that happen in the middle of the body (midline defects), and risk for tumors. The other physical features that are considered are organs larger than expected (organomegaly), issues with the skeleton, and problems with the heart, central nervous system, kidney, and gastrointestinal tract that are present from birth. A family history showing an X-linked pattern of inheritance can help with diagnosis. Genetic testing can involve sequencing and deletion/duplication analysis of the GPC3 gene, a chromosomal microarray, or a multigene panel that includes GPC3, GPC4, and other genes related to differential diagnoses. Screening
Patients with SGBS type 1 need to be screened regularly for tumors. Screening should be done every three months until they are four years old. From ages four to seven years old, screening should be done every four months. After age seven, screening should be done every 6 months. Screening should include abdominal ultrasounds, blood tests, urine tests, and chest x-rays.
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Diagnosis of Simpson-Golabi-Behmel Syndrome. Diagnosis of SGBS type 1 is made based on physical features of the patient, family history and genetic testing. There are no official criteria that are used to diagnose the condition. The main physical features are the different types of overgrowth (large body, large head, large fetus, large baby), the specific facial features, abnormalities that happen in the middle of the body (midline defects), and risk for tumors. The other physical features that are considered are organs larger than expected (organomegaly), issues with the skeleton, and problems with the heart, central nervous system, kidney, and gastrointestinal tract that are present from birth. A family history showing an X-linked pattern of inheritance can help with diagnosis. Genetic testing can involve sequencing and deletion/duplication analysis of the GPC3 gene, a chromosomal microarray, or a multigene panel that includes GPC3, GPC4, and other genes related to differential diagnoses. Screening
Patients with SGBS type 1 need to be screened regularly for tumors. Screening should be done every three months until they are four years old. From ages four to seven years old, screening should be done every four months. After age seven, screening should be done every 6 months. Screening should include abdominal ultrasounds, blood tests, urine tests, and chest x-rays.
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Therapies of Simpson-Golabi-Behmel Syndrome
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Treatment
The treatment for SGBS is based on the type of symptoms that each individual patient has. In the newborn period, right after birth, the baby’s blood sugar levels should be monitored to make sure they are not too low (hypoglycemia). The baby should also be checked to see if they are having problems breathing (airway obstruction). If the baby has any problems with their kidneys (renal anomalies) then their kidney function should also be monitored. Physical examinations should be done to check for a sideways curvature of the spine (scoliosis) during periods of time when the child is growing quickly. Social and intellectual development should also be monitored routinely. Individuals with cleft palate require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, surgeons, speech therapist, and psychologists must systematically and comprehensively plan treatment and rehabilitation. The palate may be repaired surgically or covered by an artificial device that closes or blocks the opening. Speech and language development need to be assisted by a speech therapist during the preschool years. For a complete list of different specialists to see based on the specific concern, reference the GeneReviews (listed under Internet sources) for Simpson-Golabi-Behmel Syndrome Type I. Genetic counseling is recommended for patients and their families
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Therapies of Simpson-Golabi-Behmel Syndrome. Treatment
The treatment for SGBS is based on the type of symptoms that each individual patient has. In the newborn period, right after birth, the baby’s blood sugar levels should be monitored to make sure they are not too low (hypoglycemia). The baby should also be checked to see if they are having problems breathing (airway obstruction). If the baby has any problems with their kidneys (renal anomalies) then their kidney function should also be monitored. Physical examinations should be done to check for a sideways curvature of the spine (scoliosis) during periods of time when the child is growing quickly. Social and intellectual development should also be monitored routinely. Individuals with cleft palate require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, surgeons, speech therapist, and psychologists must systematically and comprehensively plan treatment and rehabilitation. The palate may be repaired surgically or covered by an artificial device that closes or blocks the opening. Speech and language development need to be assisted by a speech therapist during the preschool years. For a complete list of different specialists to see based on the specific concern, reference the GeneReviews (listed under Internet sources) for Simpson-Golabi-Behmel Syndrome Type I. Genetic counseling is recommended for patients and their families
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Overview of Singleton Merten syndrome
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Singleton-Merten syndrome is an extremely rare, multisystem disorder the major characteristics of which are tooth abnormalities (dental dysplasia), calcifications in the aorta, the major artery of the body, and certain valves of the heart (i.e., aortic and mitral valves), as well as progressive thinning and loss of protein of the bones (osteoporosis), especially in the hands and feet. Other physical findings usually associated with Singleton-Merten syndrome may include generalized muscle weakness; progressive loss or wasting away of muscle tissue (atrophy); delayed growth, possibly resulting in short stature; delays in motor development; a skin condition characterized by thickened patches of red, scaly skin, particularly on the fingers; vision problems (glaucoma); abnormal ligaments of the joints and muscle; and/or malformation of the hips and/or feet. It appears that, in some cases, Singleton-Merten syndrome is present as a result of a random (sporadic) mutation that occurs for no apparent reason. In other cases, an autosomal dominant pattern of inheritance has been suggested.
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Overview of Singleton Merten syndrome. Singleton-Merten syndrome is an extremely rare, multisystem disorder the major characteristics of which are tooth abnormalities (dental dysplasia), calcifications in the aorta, the major artery of the body, and certain valves of the heart (i.e., aortic and mitral valves), as well as progressive thinning and loss of protein of the bones (osteoporosis), especially in the hands and feet. Other physical findings usually associated with Singleton-Merten syndrome may include generalized muscle weakness; progressive loss or wasting away of muscle tissue (atrophy); delayed growth, possibly resulting in short stature; delays in motor development; a skin condition characterized by thickened patches of red, scaly skin, particularly on the fingers; vision problems (glaucoma); abnormal ligaments of the joints and muscle; and/or malformation of the hips and/or feet. It appears that, in some cases, Singleton-Merten syndrome is present as a result of a random (sporadic) mutation that occurs for no apparent reason. In other cases, an autosomal dominant pattern of inheritance has been suggested.
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Symptoms of Singleton Merten syndrome
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Singleton-Merten syndrome, an extremely rare disorder, is characterized by abnormalities of the teeth (dental dysplasia), abnormal accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and certain valves of the heart (i.e., aortic and mitral valves), and/or progressive thinning and loss of protein of the bones (osteoporosis). Between the ages of four to 24 months, most affected infants experience generalized muscle weakness and loss or wasting away (atrophy) of muscle tissue. Affected infants may also exhibit delays in general physical (somatic) development, possibly resulting in short stature, and/or delays in the ability to coordinate muscles and perform certain tasks (motor development).Abnormalities affecting the teeth also occur at an early age in individuals with Singleton-Merten syndrome. Affected infants may develop cavities (caries) and lose their primary (deciduous) teeth prematurely. Certain secondary (permanent) teeth may not develop (erupt) or may erupt late; those permanent teeth that do develop are usually malformed (dysplastic). In some patients, permanent teeth may also be lost prematurely.By late infancy or early childhood, affected individuals may experience symptoms associated with the progressive accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and on certain valves of the heart (i.e., aortic and mitral). The aorta arises from the lower pumping chamber of the heart (left ventricle) and supplies oxygen-rich (oxygenated) blood to all the arteries of the body (excluding the pulmonary artery). In individuals with Singleton-Merten syndrome, deposits of calcium (calcifications) form in the portion of the aorta nearest the heart (proximal thoracic aorta). The accumulation of calcium deposits is progressive and typically causes blockage and narrowing of the aorta (calcific aortic stenosis), obstructing the flow of oxygenated blood. In some cases, abnormal calcium deposits may also develop around the valve on the left side of the heart (mitral valve calcification). As a result of calcification of these various structures, affected individuals may experience high blood pressure (hypertension), abnormal transmission of electrical impulses (conduction) that coordinate the activity of the heart muscle (heart block), abnormal contractions of the heart (systolic murmurs), and/or abnormal enlargement of the heart (cardiomegaly). By late adolescence, the heart may be unable to pump blood effectively (heart failure), leading to life-threatening complications.Infants with Singleton-Merten syndrome may also experience abnormal thinning and weakness of the bones (osteoporosis). As a result, bones are frequently brittle and may fracture easily. Osteoporosis may occur in the skull and the long bones of the arms and legs, but is most prominent in the bones of the hands and fingers.Other findings associated with Singleton-Merten syndrome may include malformations of the hips and feet that may occur due to muscle weakness; wearing away (erosion) of the bones in the tips of the fingers (terminal phalanges); and/or a chronic skin condition characterized by red, thick, scaly patches of skin (psoriasiform skin eruption). Some affected individuals may have abnormal accumulation of pressure of the fluid of the eye (glaucoma) and/or abnormal sensitivity to light (photosensitivity). Typical facial features have also been described in individuals with Singleton-Merten syndrome including a high anterior hairline, broad forehead, drooping of the upper eyelids (ptosis), a loss of the vertical groove between the base of the nose and upper lip (philtrum), and a thin upper lip border (vermillion).
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Symptoms of Singleton Merten syndrome. Singleton-Merten syndrome, an extremely rare disorder, is characterized by abnormalities of the teeth (dental dysplasia), abnormal accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and certain valves of the heart (i.e., aortic and mitral valves), and/or progressive thinning and loss of protein of the bones (osteoporosis). Between the ages of four to 24 months, most affected infants experience generalized muscle weakness and loss or wasting away (atrophy) of muscle tissue. Affected infants may also exhibit delays in general physical (somatic) development, possibly resulting in short stature, and/or delays in the ability to coordinate muscles and perform certain tasks (motor development).Abnormalities affecting the teeth also occur at an early age in individuals with Singleton-Merten syndrome. Affected infants may develop cavities (caries) and lose their primary (deciduous) teeth prematurely. Certain secondary (permanent) teeth may not develop (erupt) or may erupt late; those permanent teeth that do develop are usually malformed (dysplastic). In some patients, permanent teeth may also be lost prematurely.By late infancy or early childhood, affected individuals may experience symptoms associated with the progressive accumulation of calcium deposits (calcifications) in the major artery of the body (aorta) and on certain valves of the heart (i.e., aortic and mitral). The aorta arises from the lower pumping chamber of the heart (left ventricle) and supplies oxygen-rich (oxygenated) blood to all the arteries of the body (excluding the pulmonary artery). In individuals with Singleton-Merten syndrome, deposits of calcium (calcifications) form in the portion of the aorta nearest the heart (proximal thoracic aorta). The accumulation of calcium deposits is progressive and typically causes blockage and narrowing of the aorta (calcific aortic stenosis), obstructing the flow of oxygenated blood. In some cases, abnormal calcium deposits may also develop around the valve on the left side of the heart (mitral valve calcification). As a result of calcification of these various structures, affected individuals may experience high blood pressure (hypertension), abnormal transmission of electrical impulses (conduction) that coordinate the activity of the heart muscle (heart block), abnormal contractions of the heart (systolic murmurs), and/or abnormal enlargement of the heart (cardiomegaly). By late adolescence, the heart may be unable to pump blood effectively (heart failure), leading to life-threatening complications.Infants with Singleton-Merten syndrome may also experience abnormal thinning and weakness of the bones (osteoporosis). As a result, bones are frequently brittle and may fracture easily. Osteoporosis may occur in the skull and the long bones of the arms and legs, but is most prominent in the bones of the hands and fingers.Other findings associated with Singleton-Merten syndrome may include malformations of the hips and feet that may occur due to muscle weakness; wearing away (erosion) of the bones in the tips of the fingers (terminal phalanges); and/or a chronic skin condition characterized by red, thick, scaly patches of skin (psoriasiform skin eruption). Some affected individuals may have abnormal accumulation of pressure of the fluid of the eye (glaucoma) and/or abnormal sensitivity to light (photosensitivity). Typical facial features have also been described in individuals with Singleton-Merten syndrome including a high anterior hairline, broad forehead, drooping of the upper eyelids (ptosis), a loss of the vertical groove between the base of the nose and upper lip (philtrum), and a thin upper lip border (vermillion).
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Causes of Singleton Merten syndrome
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Singleton-Merten syndrome is an extremely rare disorder that is likely an autosomal dominant condition with highly variable expression. Individuals with a mild form of Singleton-Merten syndrome may show only one symptom, such as a skin rash (psoriasis). Individuals with a severe form may exhibit all the main features of Singleton-Merten syndrome including calcifications in the heart and aorta as well as skeletal and dental abnormalities. Singleton-Merten syndrome is caused by a mutation in the IFIH1 gene. This gene is responsible for making a protein called melanoma differentiation-associated gene 5 (MDA5) protein. When it functions normally, MDA5 is activated by the presence of viruses. Upon activation it leads to production of certain molecules that can increase activity of the immune system. However, the form of the MDA5 protein in individuals with Singleton-Merten syndrome appears to always be activated, even when there are no viruses present. This leads to an overactive immune system. This constant state of inflammation may promote disordered calcium metabolism in the body, leading to abnormal calcification of the aorta and heart valves and loss of calcification in the bones. There has also been another gene identified, DDX58, which has been associated with atypical Singleton-Merten syndrome. DDX58 is a gene responsible for making a protein called retinoic-acid-inducible gene (RIG-I). One family of individuals with this mutation were affected by vision problems, aortic calcification, and skeletal abnormalities but had normal dentition. Another family of individuals with this mutation had vision problems and skeletal abnormalities but had normal aortas and normal dentition.
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Causes of Singleton Merten syndrome. Singleton-Merten syndrome is an extremely rare disorder that is likely an autosomal dominant condition with highly variable expression. Individuals with a mild form of Singleton-Merten syndrome may show only one symptom, such as a skin rash (psoriasis). Individuals with a severe form may exhibit all the main features of Singleton-Merten syndrome including calcifications in the heart and aorta as well as skeletal and dental abnormalities. Singleton-Merten syndrome is caused by a mutation in the IFIH1 gene. This gene is responsible for making a protein called melanoma differentiation-associated gene 5 (MDA5) protein. When it functions normally, MDA5 is activated by the presence of viruses. Upon activation it leads to production of certain molecules that can increase activity of the immune system. However, the form of the MDA5 protein in individuals with Singleton-Merten syndrome appears to always be activated, even when there are no viruses present. This leads to an overactive immune system. This constant state of inflammation may promote disordered calcium metabolism in the body, leading to abnormal calcification of the aorta and heart valves and loss of calcification in the bones. There has also been another gene identified, DDX58, which has been associated with atypical Singleton-Merten syndrome. DDX58 is a gene responsible for making a protein called retinoic-acid-inducible gene (RIG-I). One family of individuals with this mutation were affected by vision problems, aortic calcification, and skeletal abnormalities but had normal dentition. Another family of individuals with this mutation had vision problems and skeletal abnormalities but had normal aortas and normal dentition.
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Affects of Singleton Merten syndrome
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Singleton-Merten syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. However, in reported cases, females have been affected more frequently than males (3:1). Fewer than 10 individual cases and three families (kindred) with multiple affected members have been reported in the medical literature. Atypical Singleton-Merten syndrome has been identified in two families. One family with 8 affected individuals were affected by vision problems, aortic calcification, and skeletal abnormalities but had normal dentition. Another family with 3 affected individuals had vision and skeletal abnormalities but no problems with their arteries and teeth.
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Affects of Singleton Merten syndrome. Singleton-Merten syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. However, in reported cases, females have been affected more frequently than males (3:1). Fewer than 10 individual cases and three families (kindred) with multiple affected members have been reported in the medical literature. Atypical Singleton-Merten syndrome has been identified in two families. One family with 8 affected individuals were affected by vision problems, aortic calcification, and skeletal abnormalities but had normal dentition. Another family with 3 affected individuals had vision and skeletal abnormalities but no problems with their arteries and teeth.
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Related disorders of Singleton Merten syndrome
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Symptoms of the following disorders can be similar to those of Singleton-Merten syndrome. Comparisons may be useful for a differential diagnosis:The ectodermal dysplasias (ED) are a group of diseases typically characterized by abnormalities of the head and face (craniofacial) area, the hair, teeth, nails, and/or skin. In some cases, the abnormalities associated with some of the ectodermal dysplasias may be similar to findings associated with Singleton-Merten syndrome. Some of the ectodermal dysplasias may also be characterized by abnormalities of the heart and vascular system similar to those associated with Singleton-Merten syndrome. (For more information on these disorders, choose “ectodermal dysplasia” or the exact disease name in question as your search term in the Rare Disease Database).Aicardi-Goutieres syndrome is a rare disease that affects the brain, immune system, and skin. It is characterized by early-onset severe brain dysfunction that usually results in severe intellectual and physical disability. Individuals may also have itchy, painful skin rashes (chilblains), vision problems (glaucoma), tooth loss, and foot deformities. Aicardi-Goutieres syndrome has been associated with mutations in several different genes, including the IFIH1 gene, which is the cause of Singleton-Merten syndrome.
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Related disorders of Singleton Merten syndrome. Symptoms of the following disorders can be similar to those of Singleton-Merten syndrome. Comparisons may be useful for a differential diagnosis:The ectodermal dysplasias (ED) are a group of diseases typically characterized by abnormalities of the head and face (craniofacial) area, the hair, teeth, nails, and/or skin. In some cases, the abnormalities associated with some of the ectodermal dysplasias may be similar to findings associated with Singleton-Merten syndrome. Some of the ectodermal dysplasias may also be characterized by abnormalities of the heart and vascular system similar to those associated with Singleton-Merten syndrome. (For more information on these disorders, choose “ectodermal dysplasia” or the exact disease name in question as your search term in the Rare Disease Database).Aicardi-Goutieres syndrome is a rare disease that affects the brain, immune system, and skin. It is characterized by early-onset severe brain dysfunction that usually results in severe intellectual and physical disability. Individuals may also have itchy, painful skin rashes (chilblains), vision problems (glaucoma), tooth loss, and foot deformities. Aicardi-Goutieres syndrome has been associated with mutations in several different genes, including the IFIH1 gene, which is the cause of Singleton-Merten syndrome.
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Diagnosis of Singleton Merten syndrome
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The diagnosis of Singleton-Merten syndrome may be suspected during infancy based upon the identification of characteristic physical findings (i.e., muscle weakness, muscle atrophy, dental abnormalities, and skeletal changes). A diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and/or a variety of specialized tests. The identification of calcium deposits in the aorta, in association with the other findings described above, strongly suggests a diagnosis of Singleton-Merten syndrome.X-ray tests may be used to confirm the presence and extent of calcium deposits (calcifications) in the aorta. Obstruction or narrowing (stenosis) of the heart valves, particularly the aortic and mitral valves, may be confirmed by cardiac catheterization. During this procedure, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart and measure the pressure within the heart. X-ray studies may also be performed to confirm the presence and extent of osteoporosis. Osteoporosis may be suspected when bone fractures occur more frequently than usual. X-ray tests may also reveal abnormal widening of the hollow parts of the bones that contain soft fatty tissue (bone marrow cavities) within the bones of the hands and/or feet (e.g., metacarpals, carpals, phalanges, etc.).
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Diagnosis of Singleton Merten syndrome. The diagnosis of Singleton-Merten syndrome may be suspected during infancy based upon the identification of characteristic physical findings (i.e., muscle weakness, muscle atrophy, dental abnormalities, and skeletal changes). A diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and/or a variety of specialized tests. The identification of calcium deposits in the aorta, in association with the other findings described above, strongly suggests a diagnosis of Singleton-Merten syndrome.X-ray tests may be used to confirm the presence and extent of calcium deposits (calcifications) in the aorta. Obstruction or narrowing (stenosis) of the heart valves, particularly the aortic and mitral valves, may be confirmed by cardiac catheterization. During this procedure, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart and measure the pressure within the heart. X-ray studies may also be performed to confirm the presence and extent of osteoporosis. Osteoporosis may be suspected when bone fractures occur more frequently than usual. X-ray tests may also reveal abnormal widening of the hollow parts of the bones that contain soft fatty tissue (bone marrow cavities) within the bones of the hands and/or feet (e.g., metacarpals, carpals, phalanges, etc.).
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Therapies of Singleton Merten syndrome
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TreatmentThe treatment of Singleton-Merten syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who diagnose and treat abnormalities of the heart (cardiologists), dental specialists, physical therapists, specialists who diagnose and treat conditions of the skin (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Specific therapies for the treatment of Singleton-Merten syndrome are symptomatic and supportive. Special services that may be beneficial to affected children may include special social support, physical therapy, and other medical, social, and/or vocational services. Genetic counseling will be of benefit for affected individuals and their families.
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Therapies of Singleton Merten syndrome. TreatmentThe treatment of Singleton-Merten syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who diagnose and treat abnormalities of the heart (cardiologists), dental specialists, physical therapists, specialists who diagnose and treat conditions of the skin (dermatologists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Specific therapies for the treatment of Singleton-Merten syndrome are symptomatic and supportive. Special services that may be beneficial to affected children may include special social support, physical therapy, and other medical, social, and/or vocational services. Genetic counseling will be of benefit for affected individuals and their families.
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Overview of Sinonasal Undifferentiated Carcinoma
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Sinonasal undifferentiated carcinoma (SNUC) is a rare cancer of the nasal cavity and/or paranasal sinuses. Initial symptoms range from bloody nose, runny nose, double vision, and bulging eye to chronic infections and nasal obstruction. It has been associated with several types of papilloma in the nasal cavity, which are benign, but can give rise to malignancy. Prior irradiation for other cancers has been associated with the development of SNUC in a number of cases, and has been associated with a genetic mutation known to be associated with cancer development. Most patients have not had prior irradiation, and no other causes have demonstrated to be significant, though some studies have found that woodworkers and nickel factory workers are generally more susceptible to sinonasal malignancy of all types.
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Overview of Sinonasal Undifferentiated Carcinoma. Sinonasal undifferentiated carcinoma (SNUC) is a rare cancer of the nasal cavity and/or paranasal sinuses. Initial symptoms range from bloody nose, runny nose, double vision, and bulging eye to chronic infections and nasal obstruction. It has been associated with several types of papilloma in the nasal cavity, which are benign, but can give rise to malignancy. Prior irradiation for other cancers has been associated with the development of SNUC in a number of cases, and has been associated with a genetic mutation known to be associated with cancer development. Most patients have not had prior irradiation, and no other causes have demonstrated to be significant, though some studies have found that woodworkers and nickel factory workers are generally more susceptible to sinonasal malignancy of all types.
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Symptoms of Sinonasal Undifferentiated Carcinoma
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Symptoms include bloody nose (epistaxis), runny nose (rhinorrhea), bulging eye (exopthalmos/proptosis), double vision (diplopia), nasal obstruction, and nasal infection.
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Symptoms of Sinonasal Undifferentiated Carcinoma. Symptoms include bloody nose (epistaxis), runny nose (rhinorrhea), bulging eye (exopthalmos/proptosis), double vision (diplopia), nasal obstruction, and nasal infection.
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Causes of Sinonasal Undifferentiated Carcinoma
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The nasal cavity lies just behind the nostrils and continues backward to the nasopharynx, a space just behind the nasal cavity that is contiguous with the oropharynx (the space just behind the mouth and oral cavity). The paranasal sinuses are these: the maxillary sinus under the eyes, the ethmoid and sphenoid sinuses, which are above and behind the nasal cavity, and the frontal sinuses, which lie behind the space between the eyebrows. The nasal cavity and paranasal sinuses are lined with a thin layer of tissue called Schneiderian epithelium, which has cilia, which are tiny hairs whose movements aid in pushing dirt and other contaminants out of the nasal cavity. Schneiderian epithelium gives rise to several types of papillomas, a type of benign tumor, several of which are known to give rise to cancers. The rare case of SNUC is known to arise in these papillomas. The precise localization of the Schneiderian epithelium to the nasal cavity and paranasal sinuses explains both the strict localization of this tumor, and the unique and troublesome combination of symptoms that make SNUC a difficult disease.In the original scientific paper on SNUC, seven of eight patients were smokers, and the eighth had significant occupational exposure to known carcinogens in both coal mines and chrome plating factories (13). These patients came from a wide geographical distribution, which seemed to rule out environmental factors. Several later papers failed to confirm the data on smoking as a potential cause of SNUC. A large study from Wales, Canada and Norway has presented substantial evidence that nickel refinery workers are susceptible to all sinonasal cancers with incidences of individual pathologies proportional to those in the general population, as opposed to the established association of adenocarcinoma specifically with wood workers (59)(60). However, the majority of SNUC patients are not nickel workers, so other factors as yet undefined are at work in SNUC.Retinoblastoma is a rare childhood tumor that arises in one of the layers of the eye. Treatment usually involves removal of the eye, and sometimes radiation therapy. There have been several cases of patients with retinoblastoma who have been treated with radiation and have gone on to develop SNUC many years later. In genetic studies done on several of these patients, mutations in a gene known as the retinoblastoma gene (on chromosome 13, and designated RB-1) have been found. This gene is known to stop the progression of healthy cells into cancer cells by controlling the cell division cycle, so a mutation increases the likelihood that cells will become cancerous. However, this, too, accounts for only a small number of SNUC patients.Epstein Barr virus (EBV) is a human herpes virus with the known ability to cause cancer. In the nasopharynx, which is adjacent to the nasal cavity as discussed above, EBV is known to give rise to nasopharyngeal carcinoma (NPC), and in the sinonasal region it gives rise to PSNPC. It has been fairly well established that SNUC is not caused by EBV, but some controversy over this may still exist.The bottom line is that the cause of SNUC is still undetermined.
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Causes of Sinonasal Undifferentiated Carcinoma. The nasal cavity lies just behind the nostrils and continues backward to the nasopharynx, a space just behind the nasal cavity that is contiguous with the oropharynx (the space just behind the mouth and oral cavity). The paranasal sinuses are these: the maxillary sinus under the eyes, the ethmoid and sphenoid sinuses, which are above and behind the nasal cavity, and the frontal sinuses, which lie behind the space between the eyebrows. The nasal cavity and paranasal sinuses are lined with a thin layer of tissue called Schneiderian epithelium, which has cilia, which are tiny hairs whose movements aid in pushing dirt and other contaminants out of the nasal cavity. Schneiderian epithelium gives rise to several types of papillomas, a type of benign tumor, several of which are known to give rise to cancers. The rare case of SNUC is known to arise in these papillomas. The precise localization of the Schneiderian epithelium to the nasal cavity and paranasal sinuses explains both the strict localization of this tumor, and the unique and troublesome combination of symptoms that make SNUC a difficult disease.In the original scientific paper on SNUC, seven of eight patients were smokers, and the eighth had significant occupational exposure to known carcinogens in both coal mines and chrome plating factories (13). These patients came from a wide geographical distribution, which seemed to rule out environmental factors. Several later papers failed to confirm the data on smoking as a potential cause of SNUC. A large study from Wales, Canada and Norway has presented substantial evidence that nickel refinery workers are susceptible to all sinonasal cancers with incidences of individual pathologies proportional to those in the general population, as opposed to the established association of adenocarcinoma specifically with wood workers (59)(60). However, the majority of SNUC patients are not nickel workers, so other factors as yet undefined are at work in SNUC.Retinoblastoma is a rare childhood tumor that arises in one of the layers of the eye. Treatment usually involves removal of the eye, and sometimes radiation therapy. There have been several cases of patients with retinoblastoma who have been treated with radiation and have gone on to develop SNUC many years later. In genetic studies done on several of these patients, mutations in a gene known as the retinoblastoma gene (on chromosome 13, and designated RB-1) have been found. This gene is known to stop the progression of healthy cells into cancer cells by controlling the cell division cycle, so a mutation increases the likelihood that cells will become cancerous. However, this, too, accounts for only a small number of SNUC patients.Epstein Barr virus (EBV) is a human herpes virus with the known ability to cause cancer. In the nasopharynx, which is adjacent to the nasal cavity as discussed above, EBV is known to give rise to nasopharyngeal carcinoma (NPC), and in the sinonasal region it gives rise to PSNPC. It has been fairly well established that SNUC is not caused by EBV, but some controversy over this may still exist.The bottom line is that the cause of SNUC is still undetermined.
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Affects of Sinonasal Undifferentiated Carcinoma
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There is no regional predilection for SNUC. It affects people in all countries more or less equally, based on available evidence. There is approximately a 2:1 male:female prevalence, and the average age from available published studies is 53 years old. The age range is 14 to 83 years old.
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Affects of Sinonasal Undifferentiated Carcinoma. There is no regional predilection for SNUC. It affects people in all countries more or less equally, based on available evidence. There is approximately a 2:1 male:female prevalence, and the average age from available published studies is 53 years old. The age range is 14 to 83 years old.
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Related disorders of Sinonasal Undifferentiated Carcinoma
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Olfactory neuroblastoma is a malignant tumor of the sinuses and adjacent areas of the nose (sinonasal region) that affects mainly adults and affects both sexes equally. Nasal obstruction and nosebleeds (epitaxis) are the most common symptoms. The tumor is described as locally aggressive but distant metastases occur in about 20% of cases, mainly to lymph nodes and lung. The malignancy is usually treated by surgery supplemented by radiotherapy and chemotherapy.Sinonasal neuroendocrine carcinoma (SNEC) is a very rare malignancy that is often overlooked because it is very difficult to diagnose accurately. The nasal cavity is the most common location. There appears to be a greater propensity for men than for women to acquire this disorder.Primary sinonasal nasopharyngeal-type undifferentiated carcinoma (PSNPC) is an even more rare tumor than any of the above. Both PSNPC and SNUC have been reported to be associated with Epstein-Barr virus (EBV) but the two are considered two different entities. Inverted and oncocytic papillomas are two of several types of papillomas that vary in histologic appearance. The identification of the type of papilloma is important because inverted and oncocytic papillomas are associated with the development of particularly aggressive squamous cell carcinomas. Papillomas are not uncommon, presenting in adults between 30 and 50 years of age. Men are affected twice as often as women. Nasal obstruction is the most common presenting symptom. Local excision may lead to local recurrence in 50-70% of cases, usually within 1-2 years. The recurrence does not appear to be dependent upon the histology. The length of time between recurrences is not apparently related to the risk of subsequent cancer. Human papilloma virus (HPV) has been identified in inverted papillomas.
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Related disorders of Sinonasal Undifferentiated Carcinoma. Olfactory neuroblastoma is a malignant tumor of the sinuses and adjacent areas of the nose (sinonasal region) that affects mainly adults and affects both sexes equally. Nasal obstruction and nosebleeds (epitaxis) are the most common symptoms. The tumor is described as locally aggressive but distant metastases occur in about 20% of cases, mainly to lymph nodes and lung. The malignancy is usually treated by surgery supplemented by radiotherapy and chemotherapy.Sinonasal neuroendocrine carcinoma (SNEC) is a very rare malignancy that is often overlooked because it is very difficult to diagnose accurately. The nasal cavity is the most common location. There appears to be a greater propensity for men than for women to acquire this disorder.Primary sinonasal nasopharyngeal-type undifferentiated carcinoma (PSNPC) is an even more rare tumor than any of the above. Both PSNPC and SNUC have been reported to be associated with Epstein-Barr virus (EBV) but the two are considered two different entities. Inverted and oncocytic papillomas are two of several types of papillomas that vary in histologic appearance. The identification of the type of papilloma is important because inverted and oncocytic papillomas are associated with the development of particularly aggressive squamous cell carcinomas. Papillomas are not uncommon, presenting in adults between 30 and 50 years of age. Men are affected twice as often as women. Nasal obstruction is the most common presenting symptom. Local excision may lead to local recurrence in 50-70% of cases, usually within 1-2 years. The recurrence does not appear to be dependent upon the histology. The length of time between recurrences is not apparently related to the risk of subsequent cancer. Human papilloma virus (HPV) has been identified in inverted papillomas.
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Diagnosis of Sinonasal Undifferentiated Carcinoma
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Diagnosis of Sinonasal Undifferentiated Carcinoma.
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Therapies of Sinonasal Undifferentiated Carcinoma
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The diagnosis of SNUC requires two things: a history of a mass in the nasal cavity or the sinonasal region (see symptom section above), and tissue obtained via surgery or biopsy. Neither imaging studies nor laboratory studies are required, but sometimes SNUC does not manifest itself until imaging studies are performed for other sinus problems.TreatmentThe treatment of SNUC has no firmly established protocol. What has been established is that the disease tends to recur in the same area from which it arises, and that treatment must focus on eliminating the disease via all available treatment modalities. This means the ideal treatment is a coordinated effort by a team of medical oncologists, radiation oncologists, and surgeons who are specially trained to deal with cancers that occur in this very challenging anatomical region. Treatment, therefore, involves chemotherapy, radiation therapy and surgery in some combination. Follow-up treatment can involve dental prostheses, eye prostheses, and visits with dentists and ophthalmologists, in addition to regular follow-up with the original treating doctors for cancer follow-up. This follow-up consists of regular magnetic resonance imaging (MRI) and, if necessary, tissue biopsy.
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Therapies of Sinonasal Undifferentiated Carcinoma. The diagnosis of SNUC requires two things: a history of a mass in the nasal cavity or the sinonasal region (see symptom section above), and tissue obtained via surgery or biopsy. Neither imaging studies nor laboratory studies are required, but sometimes SNUC does not manifest itself until imaging studies are performed for other sinus problems.TreatmentThe treatment of SNUC has no firmly established protocol. What has been established is that the disease tends to recur in the same area from which it arises, and that treatment must focus on eliminating the disease via all available treatment modalities. This means the ideal treatment is a coordinated effort by a team of medical oncologists, radiation oncologists, and surgeons who are specially trained to deal with cancers that occur in this very challenging anatomical region. Treatment, therefore, involves chemotherapy, radiation therapy and surgery in some combination. Follow-up treatment can involve dental prostheses, eye prostheses, and visits with dentists and ophthalmologists, in addition to regular follow-up with the original treating doctors for cancer follow-up. This follow-up consists of regular magnetic resonance imaging (MRI) and, if necessary, tissue biopsy.
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Overview of Sirenomelia
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Sirenomelia, which is also known as mermaid syndrome, is an extremely rare congenital developmental disorder characterized by anomalies of the lower spine and the lower limbs. Affected infants are born with partial or complete fusion of the legs. Additional malformations may also occur including genitourinary abnormalities, gastrointestinal abnormalities, anomalies of the lumbarsacral spine and pelvis and absence or underdevelopment (agenesis) of one or both kidneys. Affected infants may have one foot, no feet or both feet, which may be rotated externally. The tailbone is usually absent and the sacrum is partially or completely absent as well. Additional conditions may occur with sirenomelia including imperforate anus, spina bifida, and heart (cardiac) malformations. Sirenomelia is often fatal during the newborn period. The exact cause of sirenomelia is unknown, most cases occur randomly for no apparent reason (sporadically).Some sources in the medical literature classify sirenomelia as the most severe form of caudal regression syndrome, a complex developmental disorder. However, recently many researchers have indicated that sirenomelia is a similar, but distinct, disorder. NORD has a separate report on caudal regression syndrome.
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Overview of Sirenomelia. Sirenomelia, which is also known as mermaid syndrome, is an extremely rare congenital developmental disorder characterized by anomalies of the lower spine and the lower limbs. Affected infants are born with partial or complete fusion of the legs. Additional malformations may also occur including genitourinary abnormalities, gastrointestinal abnormalities, anomalies of the lumbarsacral spine and pelvis and absence or underdevelopment (agenesis) of one or both kidneys. Affected infants may have one foot, no feet or both feet, which may be rotated externally. The tailbone is usually absent and the sacrum is partially or completely absent as well. Additional conditions may occur with sirenomelia including imperforate anus, spina bifida, and heart (cardiac) malformations. Sirenomelia is often fatal during the newborn period. The exact cause of sirenomelia is unknown, most cases occur randomly for no apparent reason (sporadically).Some sources in the medical literature classify sirenomelia as the most severe form of caudal regression syndrome, a complex developmental disorder. However, recently many researchers have indicated that sirenomelia is a similar, but distinct, disorder. NORD has a separate report on caudal regression syndrome.
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Symptoms of Sirenomelia
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There are a wide range of physical malformations that can potentially occur with sirenomelia and the specific findings can vary greatly from one individual to another. Sirenomelia is associated with severe life-threatening complications and is often fatal in the first years of life. However, survival beyond infancy into later childhood or young adulthood has been reported in a handful of cases.The characteristic finding of sirenomelia is partial or complete fusion of the lower legs. The degree of severity is highly variable. Affected infants may have only one femur (the long bone of the thigh) or may have two femurs within one shaft of the skin. Affected infants may have one foot, no feet or both feet, which may be rotated so that the back of the foot is facing forward.Affected infants may also have a variety of urogenital abnormalities including absence of one or both kidneys (renal agenesis), cystic malformation of the kidneys, an absent bladder, narrowing of the urethra (urethral atresia). In addition, they may have an imperforate anus, a condition in which a thin covering blocking the anal opening or the passage that normally connects the anus and lowest part of the large intestine (rectum) fails to develop.Infants with sirenomelia may also have abnormalities affecting the sacral and lumbar spine. In some patients, abnormal front-to-back curvature of the spine (lordosis) may occur. Affected individuals may also lack external genitalia. Absence of the spleen and/or the gallbladder has also been reported.Defects affecting the abdominal wall may also occur such as protrusion of a portion of the intestines through a hole near the bellybutton (omphalocele). Some individuals with sirenomelia may have a meningomyelocele, a condition in which the membranes that cover the spine and, in some cases, the spinal cord itself protrude through a defect in the spinal column. Congenital heart defects and respiratory complications such as severe underdevelopment of the lungs (pulmonary hypoplasia) can also be associated with sirenomelia.
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Symptoms of Sirenomelia. There are a wide range of physical malformations that can potentially occur with sirenomelia and the specific findings can vary greatly from one individual to another. Sirenomelia is associated with severe life-threatening complications and is often fatal in the first years of life. However, survival beyond infancy into later childhood or young adulthood has been reported in a handful of cases.The characteristic finding of sirenomelia is partial or complete fusion of the lower legs. The degree of severity is highly variable. Affected infants may have only one femur (the long bone of the thigh) or may have two femurs within one shaft of the skin. Affected infants may have one foot, no feet or both feet, which may be rotated so that the back of the foot is facing forward.Affected infants may also have a variety of urogenital abnormalities including absence of one or both kidneys (renal agenesis), cystic malformation of the kidneys, an absent bladder, narrowing of the urethra (urethral atresia). In addition, they may have an imperforate anus, a condition in which a thin covering blocking the anal opening or the passage that normally connects the anus and lowest part of the large intestine (rectum) fails to develop.Infants with sirenomelia may also have abnormalities affecting the sacral and lumbar spine. In some patients, abnormal front-to-back curvature of the spine (lordosis) may occur. Affected individuals may also lack external genitalia. Absence of the spleen and/or the gallbladder has also been reported.Defects affecting the abdominal wall may also occur such as protrusion of a portion of the intestines through a hole near the bellybutton (omphalocele). Some individuals with sirenomelia may have a meningomyelocele, a condition in which the membranes that cover the spine and, in some cases, the spinal cord itself protrude through a defect in the spinal column. Congenital heart defects and respiratory complications such as severe underdevelopment of the lungs (pulmonary hypoplasia) can also be associated with sirenomelia.
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Causes of Sirenomelia
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The exact cause of sirenomelia is unknown. Researchers believe that both environmental and genetic factors may play a role in the development of the disorder. Most cases appear to occur randomly for no apparent reason (sporadically), which suggests environmental factors or a new mutation. Most likely, sirenomelia is multifactorial, which means that several different factors may play a causative role. In addition, different genetic factors may contribute to the disorder in different people (genetic heterogeneity).The environmental factors that play a role in the development of sirenomelia are unknown. Some individuals may have a genetic predisposition to developing the disorder. A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or “activated” under certain circumstances, such as due to particular environmental factors. Researchers believe that environmental or genetic factors have a teratogenic effect on the developing fetus. A teratogen is any substance that can disrupt the development of an embryo or fetus.In some individuals, sirenomelia is theorized to result from irregularities in early development of the blood circulating system (a disruptive vascular defect of the development of the vascular system) within the embryo. Some affected individuals have been found to have a single large artery arising from high in the abdominal cavity without the usual two arteries that normally branch out of the lower part of the aorta and carry blood to the rearward tail (caudal) end of the embryo. The single artery present (called a “steal” vessel since it essentially steals blood from the lower portion of the embryo) diverts the flow of blood which normally circulates from the aorta to the lower parts of the embryo and to the placenta. Thus the ‘steal’ vessel redirects the blood flow to the placenta without ever reaching the tail (caudal) end of the embryo. As a result of this rerouted blood flow, the steal vessel also diverts nutrients away from the blood-deprived portion of the embryo. Arteries in this caudal area are underdeveloped and tissues dependent upon them for nutrient supply fail to develop, are malformed, or arrest their growth in some incomplete stage. In individuals with sirenomelia, the lower limb bud of the embryo fails to divide into two legs. The underlying reason why these irregularities occur is unknown.
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Causes of Sirenomelia. The exact cause of sirenomelia is unknown. Researchers believe that both environmental and genetic factors may play a role in the development of the disorder. Most cases appear to occur randomly for no apparent reason (sporadically), which suggests environmental factors or a new mutation. Most likely, sirenomelia is multifactorial, which means that several different factors may play a causative role. In addition, different genetic factors may contribute to the disorder in different people (genetic heterogeneity).The environmental factors that play a role in the development of sirenomelia are unknown. Some individuals may have a genetic predisposition to developing the disorder. A person who is genetically predisposed to a disorder carries a gene (or genes) for the disease, but it may not be expressed unless it is triggered or “activated” under certain circumstances, such as due to particular environmental factors. Researchers believe that environmental or genetic factors have a teratogenic effect on the developing fetus. A teratogen is any substance that can disrupt the development of an embryo or fetus.In some individuals, sirenomelia is theorized to result from irregularities in early development of the blood circulating system (a disruptive vascular defect of the development of the vascular system) within the embryo. Some affected individuals have been found to have a single large artery arising from high in the abdominal cavity without the usual two arteries that normally branch out of the lower part of the aorta and carry blood to the rearward tail (caudal) end of the embryo. The single artery present (called a “steal” vessel since it essentially steals blood from the lower portion of the embryo) diverts the flow of blood which normally circulates from the aorta to the lower parts of the embryo and to the placenta. Thus the ‘steal’ vessel redirects the blood flow to the placenta without ever reaching the tail (caudal) end of the embryo. As a result of this rerouted blood flow, the steal vessel also diverts nutrients away from the blood-deprived portion of the embryo. Arteries in this caudal area are underdeveloped and tissues dependent upon them for nutrient supply fail to develop, are malformed, or arrest their growth in some incomplete stage. In individuals with sirenomelia, the lower limb bud of the embryo fails to divide into two legs. The underlying reason why these irregularities occur is unknown.
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Affects of Sirenomelia
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Sirenomelia affects males more often than females by a ratio of 2.7-1. The exact incidence is unknown, but sirenomelia is estimated to occur in approximately 1 in 60,000 to 100,000 births. Sirenomelia occurs with greater frequency in one twin of identical (monozygotic) twins than it does in fraternal (dizygotic) twins or individuals.
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Affects of Sirenomelia. Sirenomelia affects males more often than females by a ratio of 2.7-1. The exact incidence is unknown, but sirenomelia is estimated to occur in approximately 1 in 60,000 to 100,000 births. Sirenomelia occurs with greater frequency in one twin of identical (monozygotic) twins than it does in fraternal (dizygotic) twins or individuals.
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Related disorders of Sirenomelia
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Symptoms of the following disorders can be similar to those of sirenomelia. Comparisons may be useful for a differential diagnosis.Caudal regression syndrome is a broad term for a rare complex disorder characterized by abnormal development of the lower (caudal) end of the spine. The spine consists of many small bones (vertebrae) that collectively form the spinal column. The spinal column is generally broken down into three segments – the cervical spine, consisting of the vertebrae just below the skull; the thoracic spine, consisting of the vertebrae in the chest region; and the lumbar spine, consisting of the vertebrae of the lower back. A triangularly-shaped bony structure called the sacrum joins the lumbar portion of spine to the pelvis. The sacrum consists of five vertebrae fused together. At the end of the sacrum is the tailbone (coccyx). A wide range of abnormalities may potentially occur in infants with caudal regression syndrome including abnormal development (agenesis) of the sacrum and coccyx and abnormalities of the lumbar spine. More severe malformations may occur in some cases. Abnormalities of the lower spine can cause a variety of additional complications including joint contractures, clubfeet and disruption or damage of the end of the spinal cord may occur, potentially causing urinary incontinence. Additional anomalies of the gastrointestinal tract, kidneys, heart, respiratory system, upper limbs and upper portions of the spine can also occur. The exact cause of caudal regression syndrome is unknown. Both environmental and genetic factors are suspected to play a role in the development of the disorder. VACTERL association is a nonrandom association of birth defects that affects multiple organ systems. 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 abnormalities; (A) = anal atresia; (C) = cardiac (heart) defects; (T) = tracheal anomalies including tracheoesophageal fistula; (E) = esophageal atresia; (R) = renal (kidney) and radial abnormalities; and (L) = (other) limb abnormalities. In addition, to the above mentioned features, affected children may also exhibit less frequent abnormalities including growth deficiencies and failure to gain weight and grow at the expected rate (failure to thrive). Further low-frequency findings include facial asymmetry (hemifacial microsomia), external ear malformations, lung lobation defects, intestinal malrotation and genital anomalies. VATER/VACTERL features are more common in twinning. In some cases, the acronym VATER association is used. Some researchers have added an (S) to the VACTERL or VATER acronym to represent a single umbilical artery instead of the normal two. Mental functioning and intelligence is usually unaffected; developmental delay/intellectual disability should suggest an alternative diagnosis. The exact cause of VACTERL association is unknown. Most cases occur randomly, for no apparent reason (sporadic). (For more information on this disorder, choose “VACTERL” as your search term in the Rare Disease Database.)
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Related disorders of Sirenomelia. Symptoms of the following disorders can be similar to those of sirenomelia. Comparisons may be useful for a differential diagnosis.Caudal regression syndrome is a broad term for a rare complex disorder characterized by abnormal development of the lower (caudal) end of the spine. The spine consists of many small bones (vertebrae) that collectively form the spinal column. The spinal column is generally broken down into three segments – the cervical spine, consisting of the vertebrae just below the skull; the thoracic spine, consisting of the vertebrae in the chest region; and the lumbar spine, consisting of the vertebrae of the lower back. A triangularly-shaped bony structure called the sacrum joins the lumbar portion of spine to the pelvis. The sacrum consists of five vertebrae fused together. At the end of the sacrum is the tailbone (coccyx). A wide range of abnormalities may potentially occur in infants with caudal regression syndrome including abnormal development (agenesis) of the sacrum and coccyx and abnormalities of the lumbar spine. More severe malformations may occur in some cases. Abnormalities of the lower spine can cause a variety of additional complications including joint contractures, clubfeet and disruption or damage of the end of the spinal cord may occur, potentially causing urinary incontinence. Additional anomalies of the gastrointestinal tract, kidneys, heart, respiratory system, upper limbs and upper portions of the spine can also occur. The exact cause of caudal regression syndrome is unknown. Both environmental and genetic factors are suspected to play a role in the development of the disorder. VACTERL association is a nonrandom association of birth defects that affects multiple organ systems. 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 abnormalities; (A) = anal atresia; (C) = cardiac (heart) defects; (T) = tracheal anomalies including tracheoesophageal fistula; (E) = esophageal atresia; (R) = renal (kidney) and radial abnormalities; and (L) = (other) limb abnormalities. In addition, to the above mentioned features, affected children may also exhibit less frequent abnormalities including growth deficiencies and failure to gain weight and grow at the expected rate (failure to thrive). Further low-frequency findings include facial asymmetry (hemifacial microsomia), external ear malformations, lung lobation defects, intestinal malrotation and genital anomalies. VATER/VACTERL features are more common in twinning. In some cases, the acronym VATER association is used. Some researchers have added an (S) to the VACTERL or VATER acronym to represent a single umbilical artery instead of the normal two. Mental functioning and intelligence is usually unaffected; developmental delay/intellectual disability should suggest an alternative diagnosis. The exact cause of VACTERL association is unknown. Most cases occur randomly, for no apparent reason (sporadic). (For more information on this disorder, choose “VACTERL” as your search term in the Rare Disease Database.)
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Diagnosis of Sirenomelia
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A diagnosis of sirenomelia can be made prenatally, most often during the second trimester, by fetal ultrasound. An ultrasound is an exam that uses high-frequency sound waves to produce an image of the developing fetus. A fetal ultrasound can detect some of the defects associated with sirenomelia.
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Diagnosis of Sirenomelia. A diagnosis of sirenomelia can be made prenatally, most often during the second trimester, by fetal ultrasound. An ultrasound is an exam that uses high-frequency sound waves to produce an image of the developing fetus. A fetal ultrasound can detect some of the defects associated with sirenomelia.
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Therapies of Sirenomelia
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TreatmentTreatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, orthopedists, orthopedist surgeons, kidney specialists (nephrologists) and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Surgery has been successful in separating joined legs. In preparation for surgery, balloon-like tissue expanders are inserted under the skin. When they are filled with a salt solution over a period of time, the balloons expand making the skin stretch and grow. The excess skin is then used to cover the legs once they are separated. Sirenomelia is usually fatal in the newborn period despite treatment.
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Therapies of Sirenomelia. TreatmentTreatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, orthopedists, orthopedist surgeons, kidney specialists (nephrologists) and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Surgery has been successful in separating joined legs. In preparation for surgery, balloon-like tissue expanders are inserted under the skin. When they are filled with a salt solution over a period of time, the balloons expand making the skin stretch and grow. The excess skin is then used to cover the legs once they are separated. Sirenomelia is usually fatal in the newborn period despite treatment.
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Overview of Sitosterolemia
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SummarySitosterolemia is a rare genetic condition that causes the body to store plant sterols. There are at least two types of sterols: sterols from animals (example, cholesterol) and sterols from plants –also called phytosterols (example, sitosterol). Most people normally absorb plant sterols from the food they eat and excrete them in the gut. People with sitosterolemia absorb plant sterols but cannot excrete them, resulting in the accumulation of plant sterols in the body, especially in the blood and the arteries. Sitosterolemia is an autosomal recessive genetic condition caused by changes (mutations) in the ABCG5 or ABCG8 gene.IntroductionStandard lipid profiles do not check for plant sterol in the blood, so sitosterolemia is frequently missed unless a special blood test is ordered. Variability in presenting signs and symptoms and low awareness of this condition contribute to missed or delayed diagnosis. If left untreated, sitosterolemia can lead to premature hardening of the arteries (atherosclerosis) and premature death. However, sitosterolemia is manageable with medications that limit plant sterol absorption in the gut and with special diets that contain very little plant sterols.
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Overview of Sitosterolemia. SummarySitosterolemia is a rare genetic condition that causes the body to store plant sterols. There are at least two types of sterols: sterols from animals (example, cholesterol) and sterols from plants –also called phytosterols (example, sitosterol). Most people normally absorb plant sterols from the food they eat and excrete them in the gut. People with sitosterolemia absorb plant sterols but cannot excrete them, resulting in the accumulation of plant sterols in the body, especially in the blood and the arteries. Sitosterolemia is an autosomal recessive genetic condition caused by changes (mutations) in the ABCG5 or ABCG8 gene.IntroductionStandard lipid profiles do not check for plant sterol in the blood, so sitosterolemia is frequently missed unless a special blood test is ordered. Variability in presenting signs and symptoms and low awareness of this condition contribute to missed or delayed diagnosis. If left untreated, sitosterolemia can lead to premature hardening of the arteries (atherosclerosis) and premature death. However, sitosterolemia is manageable with medications that limit plant sterol absorption in the gut and with special diets that contain very little plant sterols.
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Sitosterolemia
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Symptoms of Sitosterolemia
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Signs and symptoms of sitosterolemia vary from person to person, but any one of these symptoms alone is reason enough to be tested for it. Some patients (especially children) present with high cholesterol. While most cases of high cholesterol are not caused by sitosterolemia, if a patient’s cholesterol varies greatly with diet, but does not respond well to statins, then it could be a sign of sitosterolemia.Patients with sitosterolemia may present with xanthomas, which are visible fatty deposits under the skin. They can be located anywhere, but frequently occur around the knees, heels, elbows, buttocks, or around the eyes. However, the absence of xanthomas should never be used to rule out sitosterolemia.Deposits of plant sterols sometimes cause joint stiffness and pain. Some sitosterolemia patients only present with blood abnormalities such as low platelet count (thrombocytopenia), abnormally large platelets (macrothrombocytopenia) or abnormally shaped red blood cells (stomatocytes).All sitosterolemia patients will have elevated levels of plant sterols in their blood (see Diagnosis section).
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Symptoms of Sitosterolemia. Signs and symptoms of sitosterolemia vary from person to person, but any one of these symptoms alone is reason enough to be tested for it. Some patients (especially children) present with high cholesterol. While most cases of high cholesterol are not caused by sitosterolemia, if a patient’s cholesterol varies greatly with diet, but does not respond well to statins, then it could be a sign of sitosterolemia.Patients with sitosterolemia may present with xanthomas, which are visible fatty deposits under the skin. They can be located anywhere, but frequently occur around the knees, heels, elbows, buttocks, or around the eyes. However, the absence of xanthomas should never be used to rule out sitosterolemia.Deposits of plant sterols sometimes cause joint stiffness and pain. Some sitosterolemia patients only present with blood abnormalities such as low platelet count (thrombocytopenia), abnormally large platelets (macrothrombocytopenia) or abnormally shaped red blood cells (stomatocytes).All sitosterolemia patients will have elevated levels of plant sterols in their blood (see Diagnosis section).
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Sitosterolemia
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Causes of Sitosterolemia
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Sitosterolemia is an autosomal recessive genetic condition caused by mutations in the ABCG5 or ABCG8 gene.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
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Causes of Sitosterolemia. Sitosterolemia is an autosomal recessive genetic condition caused by mutations in the ABCG5 or ABCG8 gene.Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
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Sitosterolemia
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Affects of Sitosterolemia
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A recent report suggests that sitosterolemia has a global prevalence of at least 1 in 2.6 million for an ABCG5 gene mutation and 1 in 360,000 for an ABCG8 gene mutation [Hooper, et al, 2016]. The routine clinical test for measuring plasma concentration of cholesterol does not measure plant sterols; therefore sitosterolemia is likely to be underdiagnosed. Men and women are equally likely to have sitosterolemia, and anyone with this condition will have had it from birth, although many are not diagnosed until later.Researchers identified one individual with sitosterolemia out of 2542 persons in whom plasma concentration of plant sterols was analyzed [Wilund et al 2004]. These researchers estimated a prevalence of 1/384 to 1/48,076.Sitosterolemia has been described in various populations, including Hutterite, Amish, Japanese, Chinese, and Indian, as well as in other populations. High prevalence has been observed in the following populations:• The Old Order Amish
• North American Hutterites
• The inhabitants of Kosrae (Micronesia)Northern European/white individuals more frequently have mutations in the ABCG8 gene. Chinese, Japanese, and Indians tend to have mutations in the ABCG5 gene.
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Affects of Sitosterolemia. A recent report suggests that sitosterolemia has a global prevalence of at least 1 in 2.6 million for an ABCG5 gene mutation and 1 in 360,000 for an ABCG8 gene mutation [Hooper, et al, 2016]. The routine clinical test for measuring plasma concentration of cholesterol does not measure plant sterols; therefore sitosterolemia is likely to be underdiagnosed. Men and women are equally likely to have sitosterolemia, and anyone with this condition will have had it from birth, although many are not diagnosed until later.Researchers identified one individual with sitosterolemia out of 2542 persons in whom plasma concentration of plant sterols was analyzed [Wilund et al 2004]. These researchers estimated a prevalence of 1/384 to 1/48,076.Sitosterolemia has been described in various populations, including Hutterite, Amish, Japanese, Chinese, and Indian, as well as in other populations. High prevalence has been observed in the following populations:• The Old Order Amish
• North American Hutterites
• The inhabitants of Kosrae (Micronesia)Northern European/white individuals more frequently have mutations in the ABCG8 gene. Chinese, Japanese, and Indians tend to have mutations in the ABCG5 gene.
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Related disorders of Sitosterolemia
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Symptoms of the following disorders can be similar to sitosterolemia.Sitosterolemia may be misdiagnosed as familial hypercholesterolemia. Patients with idiopathic thrombocytopenic purpura (ITP), a disease caused by abnormal blood platelets, should be checked for sitosterolemia since too much plant sterols in the blood have negative effects on blood platelets.
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Related disorders of Sitosterolemia. Symptoms of the following disorders can be similar to sitosterolemia.Sitosterolemia may be misdiagnosed as familial hypercholesterolemia. Patients with idiopathic thrombocytopenic purpura (ITP), a disease caused by abnormal blood platelets, should be checked for sitosterolemia since too much plant sterols in the blood have negative effects on blood platelets.
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Sitosterolemia
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Diagnosis of Sitosterolemia
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The diagnosis of sitosterolemia is established in individuals who have greatly increased plant sterol concentrations (especially sitosterol, campesterol, and stigmasterol) in the blood and tissues. Shellfish sterols can also be elevated.Since standard lipid profiles do not test for the presence of plant sterols, a blood sample will have to be sent to a lab that uses specialized techniques such gas chromatography-mass spectrometry (GC-MS) or high pressure liquid chromatography (HPLC). A blood test that reveals frank elevation in phytosterol levels is considered diagnostic for sitosterolemia. Genetic testing for mutations in the ABCG8 and ABCG5 genes is available to confirm the diagnosis.• In untreated individuals with sitosterolemia, the sitosterol concentration can be as high as 10 to 65 mg/dL. Plasma concentrations of sitosterol above 1 mg/dL are considered to be diagnostic of sitosterolemia (except in infants, in whom further testing may be necessary).False-positive results have been observed in:• Normal infants ingesting commercial infant formula (which contains plant sterols) may have a transient increase in plasma plant sterols.• Patients with cholestasis or liver disease who are on parenteral nutrition (which contains plant sterols) may be unable to effectively clear the plant sterols.• Carriers of only one gene mutation for sitosterolemia may occasionally have mildly elevated concentration of sitosterol (Note, however, that plasma concentrations of sitosterol are usually normal in carriers).False-negative results can be observed in:• Individuals using ezetimibe or ezetimibe combinations, or bile acid binding resin;AND/OR• Individuals on a diet low in plant-derived foods.Clinical Testing and Work UpPlasma concentrations of plant sterols (primarily sitosterol and campesterol) and cholesterol should be monitored, and the size, number, and distribution of xanthomas should be monitored at least every six to 12 months.Platelet count should be monitored for thrombocytopenia, complete blood count (CBC) for evidence of hemolytic anemia, spleen for splenomegaly, and liver enzymes for elevation beginning at the time of diagnosis with the frequency determined by the severity of the clinical and biochemical findings.Surveillance for atherosclerosis and coronary artery disease is suggested, with the level of monitoring determined by the severity of the clinical and biochemical findings.
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Diagnosis of Sitosterolemia. The diagnosis of sitosterolemia is established in individuals who have greatly increased plant sterol concentrations (especially sitosterol, campesterol, and stigmasterol) in the blood and tissues. Shellfish sterols can also be elevated.Since standard lipid profiles do not test for the presence of plant sterols, a blood sample will have to be sent to a lab that uses specialized techniques such gas chromatography-mass spectrometry (GC-MS) or high pressure liquid chromatography (HPLC). A blood test that reveals frank elevation in phytosterol levels is considered diagnostic for sitosterolemia. Genetic testing for mutations in the ABCG8 and ABCG5 genes is available to confirm the diagnosis.• In untreated individuals with sitosterolemia, the sitosterol concentration can be as high as 10 to 65 mg/dL. Plasma concentrations of sitosterol above 1 mg/dL are considered to be diagnostic of sitosterolemia (except in infants, in whom further testing may be necessary).False-positive results have been observed in:• Normal infants ingesting commercial infant formula (which contains plant sterols) may have a transient increase in plasma plant sterols.• Patients with cholestasis or liver disease who are on parenteral nutrition (which contains plant sterols) may be unable to effectively clear the plant sterols.• Carriers of only one gene mutation for sitosterolemia may occasionally have mildly elevated concentration of sitosterol (Note, however, that plasma concentrations of sitosterol are usually normal in carriers).False-negative results can be observed in:• Individuals using ezetimibe or ezetimibe combinations, or bile acid binding resin;AND/OR• Individuals on a diet low in plant-derived foods.Clinical Testing and Work UpPlasma concentrations of plant sterols (primarily sitosterol and campesterol) and cholesterol should be monitored, and the size, number, and distribution of xanthomas should be monitored at least every six to 12 months.Platelet count should be monitored for thrombocytopenia, complete blood count (CBC) for evidence of hemolytic anemia, spleen for splenomegaly, and liver enzymes for elevation beginning at the time of diagnosis with the frequency determined by the severity of the clinical and biochemical findings.Surveillance for atherosclerosis and coronary artery disease is suggested, with the level of monitoring determined by the severity of the clinical and biochemical findings.
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Sitosterolemia
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Therapies of Sitosterolemia
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TreatmentTreatment aims to reduce plasma concentration of plant sterols to as close as possible to normal concentrations (i.e., <1 mg/dL), to control plasma concentration of cholesterol, and to prevent xanthoma formation and/or reduce the size and number of xanthomas. Current treatment therapies focus on the following: Treatments should begin at the time of diagnosis. When tolerated, the combined treatments can decrease the plasma concentrations of cholesterol and sitosterol by 10% to 50%. Often existing xanthomas regress.Arthritis, arthralgias, anemia, thromobocytopenia, and/or splenomegaly require treatment, the first step being management of the sitosterolemia, followed by routine management of the finding (by the appropriate consultants) as needed.Sitosterolemia does not respond well to standard statin treatment.Foods with high plant sterol content including shellfish, vegetable oils, margarine, nuts, avocados, and chocolate should be avoided or taken in moderation due to increased intestinal absorption of plant sterols in people with sitosterolemia.
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Therapies of Sitosterolemia. TreatmentTreatment aims to reduce plasma concentration of plant sterols to as close as possible to normal concentrations (i.e., <1 mg/dL), to control plasma concentration of cholesterol, and to prevent xanthoma formation and/or reduce the size and number of xanthomas. Current treatment therapies focus on the following: Treatments should begin at the time of diagnosis. When tolerated, the combined treatments can decrease the plasma concentrations of cholesterol and sitosterol by 10% to 50%. Often existing xanthomas regress.Arthritis, arthralgias, anemia, thromobocytopenia, and/or splenomegaly require treatment, the first step being management of the sitosterolemia, followed by routine management of the finding (by the appropriate consultants) as needed.Sitosterolemia does not respond well to standard statin treatment.Foods with high plant sterol content including shellfish, vegetable oils, margarine, nuts, avocados, and chocolate should be avoided or taken in moderation due to increased intestinal absorption of plant sterols in people with sitosterolemia.
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Sitosterolemia
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Overview of Sjögren-Larsson Syndrome
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SummarySjögren-Larsson syndrome (SLS) is an inherited disorder characterized by scaling skin (ichthyosis), intellectual disability, speech abnormalities, and spasticity. Affected infants develop various degrees of reddened skin with fine scales soon after birth. After infancy, the skin loses its redness and dark scales often appear on the neck and under the arms. Additionally, larger plate-like thick scales may develop on the lower legs. Developmental delay, speech abnormalities and seizures may accompany skin symptoms. Spasticity in the legs typically impairs motor ability and walking. Many children with this disorder have glistening white dots or degeneration of the pigment in the retina of the eye.IntroductionSLS was first described in 1957 by Swedish physicians, Sjögren and Larsson. They reported a group of 28 interrelated patients from Vasterbotten County, Sweden, who had symptoms of what is now thought of as the clinical triad, or diagnostic signs, of Sjögren-Larsson syndrome: intellectual disability, muscle stiffness in the legs (spastic diplegia), and scaly skin from birth (congenital ichthyosis). SLS is a type of leukodystrophy, which are rare, progressive, metabolic, genetic diseases that affects the brain, spinal cord and often the peripheral nerves.
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Overview of Sjögren-Larsson Syndrome. SummarySjögren-Larsson syndrome (SLS) is an inherited disorder characterized by scaling skin (ichthyosis), intellectual disability, speech abnormalities, and spasticity. Affected infants develop various degrees of reddened skin with fine scales soon after birth. After infancy, the skin loses its redness and dark scales often appear on the neck and under the arms. Additionally, larger plate-like thick scales may develop on the lower legs. Developmental delay, speech abnormalities and seizures may accompany skin symptoms. Spasticity in the legs typically impairs motor ability and walking. Many children with this disorder have glistening white dots or degeneration of the pigment in the retina of the eye.IntroductionSLS was first described in 1957 by Swedish physicians, Sjögren and Larsson. They reported a group of 28 interrelated patients from Vasterbotten County, Sweden, who had symptoms of what is now thought of as the clinical triad, or diagnostic signs, of Sjögren-Larsson syndrome: intellectual disability, muscle stiffness in the legs (spastic diplegia), and scaly skin from birth (congenital ichthyosis). SLS is a type of leukodystrophy, which are rare, progressive, metabolic, genetic diseases that affects the brain, spinal cord and often the peripheral nerves.
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Sjögren-Larsson Syndrome
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Symptoms of Sjögren-Larsson Syndrome
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The first sign of Sjögren-Larsson syndrome is often preterm birth. Apparent at birth, the ichthyosis associated with SLS often starts as thickened skin that is yellow-brown in color (hyperkeratosis). This thickened skin eventually progresses to full scaling, especially at the neck, lower abdomen, and underarms, groin, and back of knees (flexures). Unique to SLS is the itchy characteristic of the skin (pruritis).The second feature of SLS is the stiffening of the muscles (spastic paresis). This affects the legs more often than the arms. Some individuals with SLS can walk without support, but as the stiffening worsens over time many individuals opt to use a wheelchair.The other main clinical feature of SLS is intellectual disability. Most patients reach an average developmental age of 5-6 years of age. Other features that could be seen include seizures, speech difficulty, short stature, spinal abnormalities (kyphoscoliosis), smaller head and brain (microcephaly), numbness in the hands and feet (peripheral neuropathy), widely spaced teeth, under-formed enamel of the teeth, widely spaced eyes, and uncontrolled movements of the eyes (nystagmus).The symptoms of the condition can vary, even within families. However, scaling skin (ichthyosis), intellectual disability, and muscle stiffness (spastic paresis) are always seen. The average lifespan for affected males and females is 15 years and 26 years, respectively.
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Symptoms of Sjögren-Larsson Syndrome. The first sign of Sjögren-Larsson syndrome is often preterm birth. Apparent at birth, the ichthyosis associated with SLS often starts as thickened skin that is yellow-brown in color (hyperkeratosis). This thickened skin eventually progresses to full scaling, especially at the neck, lower abdomen, and underarms, groin, and back of knees (flexures). Unique to SLS is the itchy characteristic of the skin (pruritis).The second feature of SLS is the stiffening of the muscles (spastic paresis). This affects the legs more often than the arms. Some individuals with SLS can walk without support, but as the stiffening worsens over time many individuals opt to use a wheelchair.The other main clinical feature of SLS is intellectual disability. Most patients reach an average developmental age of 5-6 years of age. Other features that could be seen include seizures, speech difficulty, short stature, spinal abnormalities (kyphoscoliosis), smaller head and brain (microcephaly), numbness in the hands and feet (peripheral neuropathy), widely spaced teeth, under-formed enamel of the teeth, widely spaced eyes, and uncontrolled movements of the eyes (nystagmus).The symptoms of the condition can vary, even within families. However, scaling skin (ichthyosis), intellectual disability, and muscle stiffness (spastic paresis) are always seen. The average lifespan for affected males and females is 15 years and 26 years, respectively.
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Sjögren-Larsson Syndrome
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Causes of Sjögren-Larsson Syndrome
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The gene that is altered in patients with Sjögren-Larsson syndrome is the aldehyde dehydrogenase 3A2 (ALDH3A2) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain. Changes (mutations) in the ALDH3A2 gene result in a lower than normal amount of an enzyme (fatty aldehyde dehydrogenase). A lower amount of this enzyme leads to the scaly and itchy skin and other features seen in Sjögren-Larsson syndrome.SLS is an autosomal recessive condition. 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 two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. Parents who are close blood 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.
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Causes of Sjögren-Larsson Syndrome. The gene that is altered in patients with Sjögren-Larsson syndrome is the aldehyde dehydrogenase 3A2 (ALDH3A2) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain. Changes (mutations) in the ALDH3A2 gene result in a lower than normal amount of an enzyme (fatty aldehyde dehydrogenase). A lower amount of this enzyme leads to the scaly and itchy skin and other features seen in Sjögren-Larsson syndrome.SLS is an autosomal recessive condition. 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 two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. Parents who are close blood 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.
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Sjögren-Larsson Syndrome
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Affects of Sjögren-Larsson Syndrome
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Sjögren-Larsson syndrome affected both males and females equally and its onset is from birth. The incidence of this condition worldwide is unknown. However, the prevalence in Sweden is 1 in every 250,000 individuals.
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Affects of Sjögren-Larsson Syndrome. Sjögren-Larsson syndrome affected both males and females equally and its onset is from birth. The incidence of this condition worldwide is unknown. However, the prevalence in Sweden is 1 in every 250,000 individuals.
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Sjögren-Larsson Syndrome
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