id
stringlengths 8
11
| title
stringlengths 14
124
| content
stringlengths 0
34k
| contents
stringlengths 20
34k
| nordid
int64 0
1.32k
| rare-disease
stringlengths 4
103
|
|---|---|---|---|---|---|
nord_1171_3
|
Affects of Sudden Infant Death Syndrome
|
SIDS can affect all infants under 1 year of age. Most deaths occur less than 6 months of age with the peak affected age between 2 and 4 months. Gender, ethnic and racial differences also exist. For example, boys are at greater risk for SIDS than girls. Also, the SIDS rate in African American infants is 2.7 times greater than the Caucasian rate in the US. Likewise, SIDS rates are increased in the American Indians and Alaskan natives as compared to Caucasians. These differences may reflect both cultural practices and genetic variations.
|
Affects of Sudden Infant Death Syndrome. SIDS can affect all infants under 1 year of age. Most deaths occur less than 6 months of age with the peak affected age between 2 and 4 months. Gender, ethnic and racial differences also exist. For example, boys are at greater risk for SIDS than girls. Also, the SIDS rate in African American infants is 2.7 times greater than the Caucasian rate in the US. Likewise, SIDS rates are increased in the American Indians and Alaskan natives as compared to Caucasians. These differences may reflect both cultural practices and genetic variations.
| 1,171 |
Sudden Infant Death Syndrome
|
nord_1171_4
|
Related disorders of Sudden Infant Death Syndrome
|
There is not necessarily a definitive relationship between the following disorders and SIDS. They are often considered in the same context because of the similarity in terms of life threatening events and/or sudden death. Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system (automatic body regulation) that is caused by a genetic mutation in the Paired-Like Homeobox gene, PHOX2B. Individuals with CCHS typically present in the newborn period, though cases are now being identified in later infancy, childhood, and adulthood. The hallmark of CCHS is alveolar hypoventilation (shallow breathing) during sleep with failure to respond to the resultant low oxygen and high carbon dioxide levels. In severe cases, individuals have hypoventilation during sleep and wakefulness. The phenotype of CCHS includes additional symptoms of autonomic nervous system dysregulation including abnormalities of heart rate and rhythm, constipation, abnormal sweating, altered temperature regulation, pupillary abnormalities, decreased perception of pain, anxiety, and more. Other associated problems include Hirschsprung Disease and tumors of neural crest origin, such as neuroblastoma, ganglioneuromas, and ganglioneuroblastomas. It is quite possible that a subset of infants dying in the first year of life and diagnosed as “SIDS” or dying after the first year of life and diagnosed as Sudden Unexpected Death of Childhood (SUDC) actually have CCHS. The definitive assessment includes performing the PHOX2B Screening Test and if negative the PHOX2B Sequencing Test. (For more information about this disorder, choose “CCHS” as your search term in Rare Disease Database.)Apparent life threatening events (ALTE) refers to a frightening episode witnessed by a caregiver where the infant has apnea (cessation of breathing), color change, limpness, and/or choking. ALTE is not a diagnosis and is only a description of the presenting event. It has multiple possible causes that can originate from any of the body systems. A short list of possible causes include gastroesophageal reflux, seizures, CCHS, respiratory infection, laryngomalacia (floppy airway that causes noisy breathing), congenital heart defect, heart rhythm problem, sepsis (overwhelming body infection), and child abuse. A baby that has been evaluated for ALTE is not at increased risk for SIDS and to date no association has been made. Long QT syndrome (LQTS) is a genetic channelopathy that causes a change in the electrical signal in the heart and can result in syncope (fainting), arrhythmia (abnormal hearth rhythm), or even sudden death. This is an inherited condition that affects the channels of the heart involved with ion transport. Individuals with Long QT Syndrome can have episodes of fainting, palpitations, or no symptoms at all. Initial evaluation requires obtaining an ECG (measurement of the electrical rhythm of the heart) and patients are often referred to a Cardiologist for further assessment. Genetic testing for known Long QT mutations will confirm the diagnosis. Studies in regard to SIDS have shown that a prolonged QT interval in the first week of life is a major risk factor for sudden death. Likely 10-15% of SIDS deaths are due to Long QT Syndrome. If identified early, medication can be provided to prevent the ECG abnormalities and sudden death. Apnea of infancy is the cessation of breathing in an infant less than 1 year of age for longer then 20 seconds which may or may not be associated with color change. Apnea of infancy can be considered central (impaired signal from the brain to breath), obstructive (problem with the airway that does not allow adequate air flow to the lungs), or mixed (combination of central and obstructive) and can be secondary to multiple medical conditions. The causes are similar in scope to those for ALTE. Sudden unexpected death of childhood (SUDC) is very rare and is the sudden death of a child older than one year of age which remains unexplained after thorough investigation. Deaths occur most often during sleep, but also include childhood deaths when awake. (For more information about this disorder, choose “SUDC” as your search term in Rare Disease Database.)
|
Related disorders of Sudden Infant Death Syndrome. There is not necessarily a definitive relationship between the following disorders and SIDS. They are often considered in the same context because of the similarity in terms of life threatening events and/or sudden death. Congenital central hypoventilation syndrome (CCHS) is a disorder of the autonomic nervous system (automatic body regulation) that is caused by a genetic mutation in the Paired-Like Homeobox gene, PHOX2B. Individuals with CCHS typically present in the newborn period, though cases are now being identified in later infancy, childhood, and adulthood. The hallmark of CCHS is alveolar hypoventilation (shallow breathing) during sleep with failure to respond to the resultant low oxygen and high carbon dioxide levels. In severe cases, individuals have hypoventilation during sleep and wakefulness. The phenotype of CCHS includes additional symptoms of autonomic nervous system dysregulation including abnormalities of heart rate and rhythm, constipation, abnormal sweating, altered temperature regulation, pupillary abnormalities, decreased perception of pain, anxiety, and more. Other associated problems include Hirschsprung Disease and tumors of neural crest origin, such as neuroblastoma, ganglioneuromas, and ganglioneuroblastomas. It is quite possible that a subset of infants dying in the first year of life and diagnosed as “SIDS” or dying after the first year of life and diagnosed as Sudden Unexpected Death of Childhood (SUDC) actually have CCHS. The definitive assessment includes performing the PHOX2B Screening Test and if negative the PHOX2B Sequencing Test. (For more information about this disorder, choose “CCHS” as your search term in Rare Disease Database.)Apparent life threatening events (ALTE) refers to a frightening episode witnessed by a caregiver where the infant has apnea (cessation of breathing), color change, limpness, and/or choking. ALTE is not a diagnosis and is only a description of the presenting event. It has multiple possible causes that can originate from any of the body systems. A short list of possible causes include gastroesophageal reflux, seizures, CCHS, respiratory infection, laryngomalacia (floppy airway that causes noisy breathing), congenital heart defect, heart rhythm problem, sepsis (overwhelming body infection), and child abuse. A baby that has been evaluated for ALTE is not at increased risk for SIDS and to date no association has been made. Long QT syndrome (LQTS) is a genetic channelopathy that causes a change in the electrical signal in the heart and can result in syncope (fainting), arrhythmia (abnormal hearth rhythm), or even sudden death. This is an inherited condition that affects the channels of the heart involved with ion transport. Individuals with Long QT Syndrome can have episodes of fainting, palpitations, or no symptoms at all. Initial evaluation requires obtaining an ECG (measurement of the electrical rhythm of the heart) and patients are often referred to a Cardiologist for further assessment. Genetic testing for known Long QT mutations will confirm the diagnosis. Studies in regard to SIDS have shown that a prolonged QT interval in the first week of life is a major risk factor for sudden death. Likely 10-15% of SIDS deaths are due to Long QT Syndrome. If identified early, medication can be provided to prevent the ECG abnormalities and sudden death. Apnea of infancy is the cessation of breathing in an infant less than 1 year of age for longer then 20 seconds which may or may not be associated with color change. Apnea of infancy can be considered central (impaired signal from the brain to breath), obstructive (problem with the airway that does not allow adequate air flow to the lungs), or mixed (combination of central and obstructive) and can be secondary to multiple medical conditions. The causes are similar in scope to those for ALTE. Sudden unexpected death of childhood (SUDC) is very rare and is the sudden death of a child older than one year of age which remains unexplained after thorough investigation. Deaths occur most often during sleep, but also include childhood deaths when awake. (For more information about this disorder, choose “SUDC” as your search term in Rare Disease Database.)
| 1,171 |
Sudden Infant Death Syndrome
|
nord_1171_5
|
Diagnosis of Sudden Infant Death Syndrome
|
SIDS is a diagnosis of exclusion which means that it is only determined as the cause of death after thorough investigation of clinical history, scene of death, and autopsy reveal no other cause.
|
Diagnosis of Sudden Infant Death Syndrome. SIDS is a diagnosis of exclusion which means that it is only determined as the cause of death after thorough investigation of clinical history, scene of death, and autopsy reveal no other cause.
| 1,171 |
Sudden Infant Death Syndrome
|
nord_1171_6
|
Therapies of Sudden Infant Death Syndrome
|
TreatmentApnea or cardiac monitors have not been found to be useful in preventing SIDS. They serve to alert a caregiver to a potentially life threatening event. However, an infant can experience significant hypoxemia (reduced oxygen content) or abrupt bradycardia (slow heart rate) before the alarm is activated.Because the diagnosis of SIDS is made after death, there is no treatment. The current recommendations are aimed at reducing risk factors that are associated with SIDS.
|
Therapies of Sudden Infant Death Syndrome. TreatmentApnea or cardiac monitors have not been found to be useful in preventing SIDS. They serve to alert a caregiver to a potentially life threatening event. However, an infant can experience significant hypoxemia (reduced oxygen content) or abrupt bradycardia (slow heart rate) before the alarm is activated.Because the diagnosis of SIDS is made after death, there is no treatment. The current recommendations are aimed at reducing risk factors that are associated with SIDS.
| 1,171 |
Sudden Infant Death Syndrome
|
nord_1172_0
|
Overview of Sudden Unexplained Death in Childhood
|
SummarySudden unexplained death in childhood (SUDC) is the sudden death of a child 12 months of age or older that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. These deaths elude our scientific understanding. SUDC cannot be predicted or prevented at this time. According to the U.S. Centers for Disease Control and Prevention, in 2018, 392 children between the ages of 1-18 years died suddenly without a clear cause of death determined. Most of these children were toddlers, aged 1-4 years; an incidence of 1.4 deaths per 100,000 toddler aged children. Research and awareness of SUDC remains limited.
|
Overview of Sudden Unexplained Death in Childhood. SummarySudden unexplained death in childhood (SUDC) is the sudden death of a child 12 months of age or older that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. These deaths elude our scientific understanding. SUDC cannot be predicted or prevented at this time. According to the U.S. Centers for Disease Control and Prevention, in 2018, 392 children between the ages of 1-18 years died suddenly without a clear cause of death determined. Most of these children were toddlers, aged 1-4 years; an incidence of 1.4 deaths per 100,000 toddler aged children. Research and awareness of SUDC remains limited.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1172_1
|
Symptoms of Sudden Unexplained Death in Childhood
|
Nearly all children with SUDC were thought to be sleeping before becoming unresponsive. Most were born as full-term singletons and their development was considered normal. Children were in their state of usual good health prior to death or had mild symptoms of illness such as cold symptoms or fever. Some children with SUDC had a history of febrile seizures, or a family history of febrile seizures. A febrile seizure is a convulsion in a child that may be caused by a spike in body temperature, often from an infection. Children aged 3 months to 5 or 6 years may have febrile seizures and they occur in 2% to 5% of all children. There is a slight tendency for them to run in families. If a child’s parents, brothers or sisters, or other close relatives have had febrile seizures, the child is a bit more likely to have them.
|
Symptoms of Sudden Unexplained Death in Childhood. Nearly all children with SUDC were thought to be sleeping before becoming unresponsive. Most were born as full-term singletons and their development was considered normal. Children were in their state of usual good health prior to death or had mild symptoms of illness such as cold symptoms or fever. Some children with SUDC had a history of febrile seizures, or a family history of febrile seizures. A febrile seizure is a convulsion in a child that may be caused by a spike in body temperature, often from an infection. Children aged 3 months to 5 or 6 years may have febrile seizures and they occur in 2% to 5% of all children. There is a slight tendency for them to run in families. If a child’s parents, brothers or sisters, or other close relatives have had febrile seizures, the child is a bit more likely to have them.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1172_2
|
Causes of Sudden Unexplained Death in Childhood
|
By definition, the cause(s) of SUDC are unknown. However, due to the lack of standardizations of death investigations, consideration of undiagnosed cases of cardiac disorders affecting the heart rhythm that are often due to genetic abnormalities, infections, and neurological conditions should be considered and ruled out. The history of febrile seizures in some children with SUDC, and their family members, demonstrate a possible correlation to sudden unexpected death In epilepsy (SUDEP) defined as the sudden, unexpected, non-traumatic, non-drowning death in an individual with epilepsy, witnessed or unwitnessed, in which the postmortem examination does not reveal an anatomical or toxicological cause for the death. Most children with witnessed SUDEP are associated with a terminal convulsion, called a tonic-clonic seizure. Examinations of the brains in a subset of children after SUDC reveal subtle abnormal development of an area deep in the temporal lobe. It is unknown whether these are a cause of seizures, a result of past seizures, are a normal variant in development and whether they have a direct association with the death.
|
Causes of Sudden Unexplained Death in Childhood. By definition, the cause(s) of SUDC are unknown. However, due to the lack of standardizations of death investigations, consideration of undiagnosed cases of cardiac disorders affecting the heart rhythm that are often due to genetic abnormalities, infections, and neurological conditions should be considered and ruled out. The history of febrile seizures in some children with SUDC, and their family members, demonstrate a possible correlation to sudden unexpected death In epilepsy (SUDEP) defined as the sudden, unexpected, non-traumatic, non-drowning death in an individual with epilepsy, witnessed or unwitnessed, in which the postmortem examination does not reveal an anatomical or toxicological cause for the death. Most children with witnessed SUDEP are associated with a terminal convulsion, called a tonic-clonic seizure. Examinations of the brains in a subset of children after SUDC reveal subtle abnormal development of an area deep in the temporal lobe. It is unknown whether these are a cause of seizures, a result of past seizures, are a normal variant in development and whether they have a direct association with the death.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1172_3
|
Affects of Sudden Unexplained Death in Childhood
|
Children who die of SUDC are generally toddlers (60%), between 1 and 4 years of age, but older children can be affected. According to the CDC, non-Hispanic black/African American children have a >2-fold risk of SUDC versus non-Hispanic white, Asian or Pacific Islander, and American Indian/Alaska Native. Nearly 90% are born full-term and nearly half are first born.
|
Affects of Sudden Unexplained Death in Childhood. Children who die of SUDC are generally toddlers (60%), between 1 and 4 years of age, but older children can be affected. According to the CDC, non-Hispanic black/African American children have a >2-fold risk of SUDC versus non-Hispanic white, Asian or Pacific Islander, and American Indian/Alaska Native. Nearly 90% are born full-term and nearly half are first born.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1172_4
|
Related disorders of Sudden Unexplained Death in Childhood
|
Symptoms of the following disorders can be similar to those of SUDC. Comparisons may be useful to distinguish them from SUDC. Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected, non-traumatic, non-drowning death in an individual with epilepsy, witnessed or unwitnessed, in which the autopsy does not reveal an anatomical or toxicological (for example, poisoning) cause for the death. SUDEP typically occurs when a person with epilepsy dies unexpectedly and was in their usual state of health. The death is not known to be related to an accident or prolonged seizure (known as status epilepticus). When an autopsy is done, no other of cause of death can be found. Each year, more than 1 out of 1,000 people with epilepsy die from SUDEP. However, it occurs more frequently in people whose seizures are poorly controlled. Factors that may increase SUDEP risk include seizures that cause airway obstruction (for example, when the person is face down in the bedding), cessation of breathing and fluid in the lungs after a seizure, abnormal electrical rhythms in the heart, and very low levels of antiepileptic medications. Sudden arrhythmia death syndromes (SADS) are genetic heart conditions that can cause sudden death in young, apparently healthy, people. These conditions can be treated and deaths can be prevented. Because SADS may be passed down from parent to child, each child of an affected parent has a 50% chance of inheriting the condition. Approximately half of the 4,000 SADS deaths each year of children, teens, or young adults have one of the top two warning signs: 1) family history – of a SADS diagnosis or sudden unexplained death (usually undiagnosed and untreated), or 2) fainting. SADS conditions occur because the electrical system of the heart is not working properly, so that the heart beats with an abnormal rhythm. Each year in the United States, approximately 210,000 Americans die suddenly and unexpectedly due to sudden cardiac arrest. (American Heart Association, 2017). 10-12% of sudden infant death syndrome (SIDS) deaths are due to long QT syndrome (LQTS). LQTS is 3 times more common in the US than childhood leukemia. 1 in 200,000 high school athletes in the US will die suddenly, most without any prior symptoms (JAMA 1996; 276) Inborn errors of metabolism can also be sometimes responsible for sudden deaths in the young. They are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down food into usable energy.
|
Related disorders of Sudden Unexplained Death in Childhood. Symptoms of the following disorders can be similar to those of SUDC. Comparisons may be useful to distinguish them from SUDC. Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected, non-traumatic, non-drowning death in an individual with epilepsy, witnessed or unwitnessed, in which the autopsy does not reveal an anatomical or toxicological (for example, poisoning) cause for the death. SUDEP typically occurs when a person with epilepsy dies unexpectedly and was in their usual state of health. The death is not known to be related to an accident or prolonged seizure (known as status epilepticus). When an autopsy is done, no other of cause of death can be found. Each year, more than 1 out of 1,000 people with epilepsy die from SUDEP. However, it occurs more frequently in people whose seizures are poorly controlled. Factors that may increase SUDEP risk include seizures that cause airway obstruction (for example, when the person is face down in the bedding), cessation of breathing and fluid in the lungs after a seizure, abnormal electrical rhythms in the heart, and very low levels of antiepileptic medications. Sudden arrhythmia death syndromes (SADS) are genetic heart conditions that can cause sudden death in young, apparently healthy, people. These conditions can be treated and deaths can be prevented. Because SADS may be passed down from parent to child, each child of an affected parent has a 50% chance of inheriting the condition. Approximately half of the 4,000 SADS deaths each year of children, teens, or young adults have one of the top two warning signs: 1) family history – of a SADS diagnosis or sudden unexplained death (usually undiagnosed and untreated), or 2) fainting. SADS conditions occur because the electrical system of the heart is not working properly, so that the heart beats with an abnormal rhythm. Each year in the United States, approximately 210,000 Americans die suddenly and unexpectedly due to sudden cardiac arrest. (American Heart Association, 2017). 10-12% of sudden infant death syndrome (SIDS) deaths are due to long QT syndrome (LQTS). LQTS is 3 times more common in the US than childhood leukemia. 1 in 200,000 high school athletes in the US will die suddenly, most without any prior symptoms (JAMA 1996; 276) Inborn errors of metabolism can also be sometimes responsible for sudden deaths in the young. They are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down food into usable energy.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1172_5
|
Diagnosis of Sudden Unexplained Death in Childhood
|
SUDC is not a diagnosis but a category of death. SUDC describes the sudden death of a child greater than 12 months of age that has undergone a thorough investigation and does not reveal evidence of an unnatural death. Death investigations also vary widely and therefore the extent to which known causes of death have been ruled should be reviewed. In 2019, the National Association of Medical Examiners Panel on Sudden Unexpected Death In Pediatrics published national guidelines regarding the investigation, certification and family needs associated with sudden death in children. (https://sudpeds.com/) Clinical Testing and Work Up
The investigation of the child’s death should be comprehensive including investigation of the scene where the child was found unresponsive, interviews with caregivers, a review of the child medical history and their family medical history, a complete autopsy with ancillary testing as clinically indicated. SUDC is a multidisciplinary problem and requires coordination among the professionals involved to effectively investigate a case of SUDC and also provide appropriate communication and effective medical follow-up for family members. Families need effective communication in regards to the ramifications of the child’s final cause of death and what screening recommendations are appropriate to consider. Asking your primary care physician to collaborate with the medical examiner or coroner who performed the death investigation can be an excellent way to streamline communication in an emotionally traumatic and confusing situation. Since genetic disorders can contribute to sudden death, evaluation of family members is indicated. This can include but not limited to inherited heart arrhythmia seizure disorders, and metabolic disorders. It is valuable to confirm a family diagnosis and assess the risk in the living family members following an unexplained death. Clinical evaluation of family members following a sudden death may identify other affected members. First degree relatives (parents and siblings of the person who has died) should speak to their primary physician to obtain a referral to a cardiologist with expertise in electrophysiology and special training to evaluate genetic cardiac disorders and other referrals as clinically indicated.
|
Diagnosis of Sudden Unexplained Death in Childhood. SUDC is not a diagnosis but a category of death. SUDC describes the sudden death of a child greater than 12 months of age that has undergone a thorough investigation and does not reveal evidence of an unnatural death. Death investigations also vary widely and therefore the extent to which known causes of death have been ruled should be reviewed. In 2019, the National Association of Medical Examiners Panel on Sudden Unexpected Death In Pediatrics published national guidelines regarding the investigation, certification and family needs associated with sudden death in children. (https://sudpeds.com/) Clinical Testing and Work Up
The investigation of the child’s death should be comprehensive including investigation of the scene where the child was found unresponsive, interviews with caregivers, a review of the child medical history and their family medical history, a complete autopsy with ancillary testing as clinically indicated. SUDC is a multidisciplinary problem and requires coordination among the professionals involved to effectively investigate a case of SUDC and also provide appropriate communication and effective medical follow-up for family members. Families need effective communication in regards to the ramifications of the child’s final cause of death and what screening recommendations are appropriate to consider. Asking your primary care physician to collaborate with the medical examiner or coroner who performed the death investigation can be an excellent way to streamline communication in an emotionally traumatic and confusing situation. Since genetic disorders can contribute to sudden death, evaluation of family members is indicated. This can include but not limited to inherited heart arrhythmia seizure disorders, and metabolic disorders. It is valuable to confirm a family diagnosis and assess the risk in the living family members following an unexplained death. Clinical evaluation of family members following a sudden death may identify other affected members. First degree relatives (parents and siblings of the person who has died) should speak to their primary physician to obtain a referral to a cardiologist with expertise in electrophysiology and special training to evaluate genetic cardiac disorders and other referrals as clinically indicated.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1172_6
|
Therapies of Sudden Unexplained Death in Childhood
|
SUDC is a category of death diagnosis of exclusion which means that it is only determined after the death and thorough investigation of the clinical history, scene of death and autopsy reveal no other cause. Because the determination of SUDC is made after death, there is no treatment.
|
Therapies of Sudden Unexplained Death in Childhood. SUDC is a category of death diagnosis of exclusion which means that it is only determined after the death and thorough investigation of the clinical history, scene of death and autopsy reveal no other cause. Because the determination of SUDC is made after death, there is no treatment.
| 1,172 |
Sudden Unexplained Death in Childhood
|
nord_1173_0
|
Overview of Superficial Siderosis
|
SummaryInfratentorial superficial siderosis, commonly identified as superficial siderosis, is a disabling degenerative disorder affecting the brain and spinal cord. Persistent or recurring long-term bleeding (hemorrhage) into the subarachnoid space in the brain results in a toxic build-up of hemosiderin (an important component of iron delivery) on the surface of the brain and pia mater from circulating cerebrospinal fluid. Patients will present with one or more of the classic triad of symptoms: hearing loss, movement abnormalities (ataxia), and motor difficulties due to suspected spinal cord injury (myelopathy) with pyramidal signs. Proper recognition and timely early diagnosis of superficial siderosis allow for early care planning.
|
Overview of Superficial Siderosis. SummaryInfratentorial superficial siderosis, commonly identified as superficial siderosis, is a disabling degenerative disorder affecting the brain and spinal cord. Persistent or recurring long-term bleeding (hemorrhage) into the subarachnoid space in the brain results in a toxic build-up of hemosiderin (an important component of iron delivery) on the surface of the brain and pia mater from circulating cerebrospinal fluid. Patients will present with one or more of the classic triad of symptoms: hearing loss, movement abnormalities (ataxia), and motor difficulties due to suspected spinal cord injury (myelopathy) with pyramidal signs. Proper recognition and timely early diagnosis of superficial siderosis allow for early care planning.
| 1,173 |
Superficial Siderosis
|
nord_1173_1
|
Symptoms of Superficial Siderosis
|
Typically, the period between the onset of noticeable clinical symptoms and the trigger event ranges between 10-30 years. Symptoms and signs will present depending on the location of hemosiderin deposition and state of weakness of neural tissue. The intensity of deposition shown on imaging will not always correspond with the degree of disability due to the slow-moving progressive nature of the disorder. 95% of patients will exhibit progressive hearing impairment in both ears. 88% of patients will show signs of progressive ataxia with a focus on wide-based gait and balance issues. 76% will experience myelopathy with pyramidal signs. Additional signs include mild cognitive impairment, uncontrolled eye movements (nystagmus), poor coordination (dysmetria), difficulty swallowing (dysphagia), uncontrolled muscle movements (spasticity), loss of smell (anosmia), loss of taste (ageusia), different pupil sizes in the eyes (anisocoria) bladder or bowel dysfunction, sensory defects, small motor dysfunction, nerve pain (neuropathy), headache, autonomic nervous system dysfunction, inability to perform rapid, coordinated movements (dysdiadochokinesia), slurred speech (dysarthria), overactive reflexes (hyperreflexia) and abnormal foot reflexes (Babinski signs) Cortical superficial siderosis (cSS) is a recognized variant of superficial siderosis. Hemosiderin deposition is limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the cerebellum, brainstem and spinal cord affected in the classic iSS symptoms. Identified with gradient recalled echo (GRE) or susceptibility-weighted imaging (SWI) MRI as linear hypointensities, cortical superficial siderosis (cSS) is often due to cerebral amyloid angiopathy, an age-related cerebral small vessel disorder. Symptoms of amyloid angiopathy include transient focal neurological episodes, cognitive impairment, generalized seizures, headaches, and increased intracerebral hemorrhage risk.
|
Symptoms of Superficial Siderosis. Typically, the period between the onset of noticeable clinical symptoms and the trigger event ranges between 10-30 years. Symptoms and signs will present depending on the location of hemosiderin deposition and state of weakness of neural tissue. The intensity of deposition shown on imaging will not always correspond with the degree of disability due to the slow-moving progressive nature of the disorder. 95% of patients will exhibit progressive hearing impairment in both ears. 88% of patients will show signs of progressive ataxia with a focus on wide-based gait and balance issues. 76% will experience myelopathy with pyramidal signs. Additional signs include mild cognitive impairment, uncontrolled eye movements (nystagmus), poor coordination (dysmetria), difficulty swallowing (dysphagia), uncontrolled muscle movements (spasticity), loss of smell (anosmia), loss of taste (ageusia), different pupil sizes in the eyes (anisocoria) bladder or bowel dysfunction, sensory defects, small motor dysfunction, nerve pain (neuropathy), headache, autonomic nervous system dysfunction, inability to perform rapid, coordinated movements (dysdiadochokinesia), slurred speech (dysarthria), overactive reflexes (hyperreflexia) and abnormal foot reflexes (Babinski signs) Cortical superficial siderosis (cSS) is a recognized variant of superficial siderosis. Hemosiderin deposition is limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the cerebellum, brainstem and spinal cord affected in the classic iSS symptoms. Identified with gradient recalled echo (GRE) or susceptibility-weighted imaging (SWI) MRI as linear hypointensities, cortical superficial siderosis (cSS) is often due to cerebral amyloid angiopathy, an age-related cerebral small vessel disorder. Symptoms of amyloid angiopathy include transient focal neurological episodes, cognitive impairment, generalized seizures, headaches, and increased intracerebral hemorrhage risk.
| 1,173 |
Superficial Siderosis
|
nord_1173_2
|
Causes of Superficial Siderosis
|
Superficial siderosis is an acquired disorder caused by chronic long-term subarachnoid bleeding. A large percentage of the identifiable bleed sources are abnormalities resulting from recurring brain bleeds (chronic suboccipital hematomas), sacs protruding from the spinal column (meningoceles) or spinal surgery tears resulting in pseudomeningoceles. Other causes include root avulsions or epidural cyst removal, intradural cranial surgery, brain tumors, vascular abnormalities, fragile capillary regrowth after brain surgery, nerve damage (brachial plexus injury), head injury or bone marrow exposed to the spinal (intrathecal) space.Ruptured blood cells (hemolysis) in the cerebrospinal fluid create a heme overload that triggers Bergman glia and microglial cells into producing the enzyme heme oxygenase-1. HO-1 breaks down the heme molecule resulting in the release of free-iron molecules, carbon dioxide, and biliverdin. Astrocytes release ferritin proteins to curb the free-iron molecules and the product is hemosiderin. Because hemosiderin is not soluble, gravity pulls it to the subpial surfaces in the infratentorium and spinal column where it attaches to the pia mater. Sleeping in the supine position leads to large accumulations in the cerebellum. Cranial nerve sections, brainstem, and the spinal cord may also become encased in hemosiderin. Long-term exposure to free-iron molecules released from the hemosiderin layer is toxic to the underlying neural tissue.
|
Causes of Superficial Siderosis. Superficial siderosis is an acquired disorder caused by chronic long-term subarachnoid bleeding. A large percentage of the identifiable bleed sources are abnormalities resulting from recurring brain bleeds (chronic suboccipital hematomas), sacs protruding from the spinal column (meningoceles) or spinal surgery tears resulting in pseudomeningoceles. Other causes include root avulsions or epidural cyst removal, intradural cranial surgery, brain tumors, vascular abnormalities, fragile capillary regrowth after brain surgery, nerve damage (brachial plexus injury), head injury or bone marrow exposed to the spinal (intrathecal) space.Ruptured blood cells (hemolysis) in the cerebrospinal fluid create a heme overload that triggers Bergman glia and microglial cells into producing the enzyme heme oxygenase-1. HO-1 breaks down the heme molecule resulting in the release of free-iron molecules, carbon dioxide, and biliverdin. Astrocytes release ferritin proteins to curb the free-iron molecules and the product is hemosiderin. Because hemosiderin is not soluble, gravity pulls it to the subpial surfaces in the infratentorium and spinal column where it attaches to the pia mater. Sleeping in the supine position leads to large accumulations in the cerebellum. Cranial nerve sections, brainstem, and the spinal cord may also become encased in hemosiderin. Long-term exposure to free-iron molecules released from the hemosiderin layer is toxic to the underlying neural tissue.
| 1,173 |
Superficial Siderosis
|
nord_1173_3
|
Affects of Superficial Siderosis
|
Superficial siderosis affects all races and age groups, with males affected at three times more often than females. The prevalence of superficial siderosis is estimated to be 1 in one million individuals. In the U.S., in 2020 there are an estimated 200 diagnosed cases, almost double the number of confirmed diagnosed patients in 2014. This increase is due to improved MRI techniques and neuro-radiologist awareness. The actual incidence of superficial siderosis is suspected to affect a larger population than is currently diagnosed.
|
Affects of Superficial Siderosis. Superficial siderosis affects all races and age groups, with males affected at three times more often than females. The prevalence of superficial siderosis is estimated to be 1 in one million individuals. In the U.S., in 2020 there are an estimated 200 diagnosed cases, almost double the number of confirmed diagnosed patients in 2014. This increase is due to improved MRI techniques and neuro-radiologist awareness. The actual incidence of superficial siderosis is suspected to affect a larger population than is currently diagnosed.
| 1,173 |
Superficial Siderosis
|
nord_1173_4
|
Related disorders of Superficial Siderosis
|
Due to overlapping similarities, superficial siderosis is most often misidentified as multiple sclerosis, Parkinson's disease or multiple system atrophy.
|
Related disorders of Superficial Siderosis. Due to overlapping similarities, superficial siderosis is most often misidentified as multiple sclerosis, Parkinson's disease or multiple system atrophy.
| 1,173 |
Superficial Siderosis
|
nord_1173_5
|
Diagnosis of Superficial Siderosis
|
The average time from the clinical manifestation of early symptoms such as ringing of the ears (tinnitus), complaints of dizziness, or reports of phantom odors to the diagnosis of superficial siderosis may be as long as ten years, partly due to the slow progression of the disease. Clinical investigation of patient complaints should be reviewed against the long-term medical history focusing on previous surgical procedures, aneurysm, traumatic contusions or accidents occurring as long as thirty to forty years in the past with older patients.MRI sequencing is required to confirm the diagnosis. Superficial siderosis will be characterized as a rim of low signal covering the subpial surfaces of the brain, brainstem, and spinal cord, particularly on the gradient-echo (GRE) or susceptibility-weighted (SWI) sequences. Ependymal hypointensity may also occur in severe forms of superficial siderosis.
|
Diagnosis of Superficial Siderosis. The average time from the clinical manifestation of early symptoms such as ringing of the ears (tinnitus), complaints of dizziness, or reports of phantom odors to the diagnosis of superficial siderosis may be as long as ten years, partly due to the slow progression of the disease. Clinical investigation of patient complaints should be reviewed against the long-term medical history focusing on previous surgical procedures, aneurysm, traumatic contusions or accidents occurring as long as thirty to forty years in the past with older patients.MRI sequencing is required to confirm the diagnosis. Superficial siderosis will be characterized as a rim of low signal covering the subpial surfaces of the brain, brainstem, and spinal cord, particularly on the gradient-echo (GRE) or susceptibility-weighted (SWI) sequences. Ependymal hypointensity may also occur in severe forms of superficial siderosis.
| 1,173 |
Superficial Siderosis
|
nord_1173_6
|
Therapies of Superficial Siderosis
|
The first step after a diagnosis is determining if a bleed source is present. Despite an investigation, a cause is not identified for a large percentage of patients. A CT myelogram is the preferred method to determine the location of a suspected bleed due to dural defect. The three suggested approaches for stopping a bleed are injection of fibrin glue into the dural tear site; for small leaks, an epidural blood patch may pull the dura from surrounding bone and immobilize the spinal cord long enough for healing to take place. Surgical closure of dural defects or other active bleed sites offers the best opportunity to stop additional hemosiderin deposition.The progression of neurological deficits will continue as long as free-iron molecules continue to release from existing hemosiderin. Elimination of hemosiderin deposition off the subpial surface is fundamental to potentially stopping cerebellar atrophy and neural damage. This removal action must be accomplished through iron chelation. In order for a chelating agent to achieve its desired pharmacological effect, the drug must reach the target sites at sufficient concentration. Deferiprone is an orally active bidentate hydroxypyridinone iron chelator proven to cross the blood-brain barrier that binds to ferric ions (fe3+), forms a 3:1 chelator to iron stable complex, and is eliminated through urine. One reason for the limited efficacy of deferiprone in clinical use is its extensive metabolism in the liver. Patients prescribed deferiprone require close monitoring due to the severe nature of possible side effects, most notably being a low incidence of reversible agranulocytosis.Patient care will rely on the coordinated treatment of the underlying symptoms through referral to appropriate specialties. The superficial siderosis patient in mid to late-stage progression lives in a state of compromised neurological reserve on a perpetual basis. They may require a longer than average recovery time from procedures, surgery, or illness. Consideration should be given for neuropsychological evaluation with increasing patterns of cognitive and social impairment, memory problems, or behavioral changes. 20% of those diagnosed with mild or progressive cognitive impairment initially may progress to neurodegenerative dementia.
|
Therapies of Superficial Siderosis. The first step after a diagnosis is determining if a bleed source is present. Despite an investigation, a cause is not identified for a large percentage of patients. A CT myelogram is the preferred method to determine the location of a suspected bleed due to dural defect. The three suggested approaches for stopping a bleed are injection of fibrin glue into the dural tear site; for small leaks, an epidural blood patch may pull the dura from surrounding bone and immobilize the spinal cord long enough for healing to take place. Surgical closure of dural defects or other active bleed sites offers the best opportunity to stop additional hemosiderin deposition.The progression of neurological deficits will continue as long as free-iron molecules continue to release from existing hemosiderin. Elimination of hemosiderin deposition off the subpial surface is fundamental to potentially stopping cerebellar atrophy and neural damage. This removal action must be accomplished through iron chelation. In order for a chelating agent to achieve its desired pharmacological effect, the drug must reach the target sites at sufficient concentration. Deferiprone is an orally active bidentate hydroxypyridinone iron chelator proven to cross the blood-brain barrier that binds to ferric ions (fe3+), forms a 3:1 chelator to iron stable complex, and is eliminated through urine. One reason for the limited efficacy of deferiprone in clinical use is its extensive metabolism in the liver. Patients prescribed deferiprone require close monitoring due to the severe nature of possible side effects, most notably being a low incidence of reversible agranulocytosis.Patient care will rely on the coordinated treatment of the underlying symptoms through referral to appropriate specialties. The superficial siderosis patient in mid to late-stage progression lives in a state of compromised neurological reserve on a perpetual basis. They may require a longer than average recovery time from procedures, surgery, or illness. Consideration should be given for neuropsychological evaluation with increasing patterns of cognitive and social impairment, memory problems, or behavioral changes. 20% of those diagnosed with mild or progressive cognitive impairment initially may progress to neurodegenerative dementia.
| 1,173 |
Superficial Siderosis
|
nord_1174_0
|
Overview of Superior Mesenteric Artery Syndrome
|
SummarySuperior mesenteric artery (SMA) syndrome is a rare condition that involves compression of the third portion of the duodenum which is the upper part of the small intestines just past the stomach. This condition occurs when the third part of the duodenum is compressed between two arteries – the main artery of the body called the abdominal aorta (AA) and one of its branches called the SMA. The SMA provides blood supply to the small intestines and the first part of the colon. Compression of the SMA against the AA can prevent duodenal contents from draining into the jejunum (upper small intestine) hence the inability to get proper nutrition leading to weight loss and malnutrition. Pain from the compression can be debilitating, causing “food fear” and aggravating the condition. Nausea and vomiting are manifestations of the compression of the duodenum. When weight loss is persistent, the mesenteric fat pad decreases and causes a decrease in the angle between the SMA and AA hence aggravating the compression and obstruction. Prompt diagnosis and early treatment are essential to avoid significant complications or death.IntroductionSMA syndrome is considered extremely uncommon and most consider this as a diagnosis of exclusion i.e., many other more common diagnoses must be ruled out.
|
Overview of Superior Mesenteric Artery Syndrome. SummarySuperior mesenteric artery (SMA) syndrome is a rare condition that involves compression of the third portion of the duodenum which is the upper part of the small intestines just past the stomach. This condition occurs when the third part of the duodenum is compressed between two arteries – the main artery of the body called the abdominal aorta (AA) and one of its branches called the SMA. The SMA provides blood supply to the small intestines and the first part of the colon. Compression of the SMA against the AA can prevent duodenal contents from draining into the jejunum (upper small intestine) hence the inability to get proper nutrition leading to weight loss and malnutrition. Pain from the compression can be debilitating, causing “food fear” and aggravating the condition. Nausea and vomiting are manifestations of the compression of the duodenum. When weight loss is persistent, the mesenteric fat pad decreases and causes a decrease in the angle between the SMA and AA hence aggravating the compression and obstruction. Prompt diagnosis and early treatment are essential to avoid significant complications or death.IntroductionSMA syndrome is considered extremely uncommon and most consider this as a diagnosis of exclusion i.e., many other more common diagnoses must be ruled out.
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1174_1
|
Symptoms of Superior Mesenteric Artery Syndrome
|
The signs and symptoms can vary greatly from one person to another. Sometimes the symptoms are mild and build slowly over time. Without treatment, in some people, symptoms can be severely disabling. Generally, the initial symptoms are nonspecific, which means that symptoms are common ones that can be associated with many different conditions. Sometimes symptoms can come and go (intermittent). Symptoms can include nausea, vomiting, abdominal pain, indigestion (dyspepsia) and early satiety, in which the person feels full despite having very little food or drink because the stomach is not emptying. The stomach remains full of fluid or food previously ingested hours before. Constipation can occur when there is delay in stomach emptying. Vomiting of undigested food can occur and can become bilious i.e., green or yellow when the blockage becomes severe. Relief can be obtained by lying on the right decubitus or left decubitus (right or left side down) or face down (prone) with both arms and legs up (knee to chest position) after eating or drinking to allow the stomach to empty better. The abdominal pain can be severe after intake of food or drink because the pulsation of the SMA becomes stronger and bounding against the duodenum. Food aversion or food fear follows which aggravates the weight loss and worsens SMA syndrome.Some affected individuals may also have nutcracker syndrome in which the left renal vein (kidney vein) is compressed by the AA and SMA. Most people affected have no symptoms but those affected will have left flank and pelvic pain and may have blood in the urine (hematuria).
|
Symptoms of Superior Mesenteric Artery Syndrome. The signs and symptoms can vary greatly from one person to another. Sometimes the symptoms are mild and build slowly over time. Without treatment, in some people, symptoms can be severely disabling. Generally, the initial symptoms are nonspecific, which means that symptoms are common ones that can be associated with many different conditions. Sometimes symptoms can come and go (intermittent). Symptoms can include nausea, vomiting, abdominal pain, indigestion (dyspepsia) and early satiety, in which the person feels full despite having very little food or drink because the stomach is not emptying. The stomach remains full of fluid or food previously ingested hours before. Constipation can occur when there is delay in stomach emptying. Vomiting of undigested food can occur and can become bilious i.e., green or yellow when the blockage becomes severe. Relief can be obtained by lying on the right decubitus or left decubitus (right or left side down) or face down (prone) with both arms and legs up (knee to chest position) after eating or drinking to allow the stomach to empty better. The abdominal pain can be severe after intake of food or drink because the pulsation of the SMA becomes stronger and bounding against the duodenum. Food aversion or food fear follows which aggravates the weight loss and worsens SMA syndrome.Some affected individuals may also have nutcracker syndrome in which the left renal vein (kidney vein) is compressed by the AA and SMA. Most people affected have no symptoms but those affected will have left flank and pelvic pain and may have blood in the urine (hematuria).
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1174_2
|
Causes of Superior Mesenteric Artery Syndrome
|
SMA syndrome occurs when the duodenum is compressed by the SMA against the AA to cause blockage and prevent progression of food or fluids into the rest of the small intestine. The small intestine is a long, winding tube that connects the stomach to the large intestine ending in the anus. The small intestine is divided into three sections – duodenum, jejunum and ileum. Each section has a role in digestion and absorption of nutrients that were previously digested in the stomach. The duodenum is the first part of the small intestine and directly connects to the stomach. It has four parts or sections. The third section can be compressed by the SMA against the AA causing a partial obstruction which manifests as nausea, vomiting and epigastric pain. The mesentery is a double fold that suspends the small intestine and large intestine from the posterior abdominal wall. Loss of the mesenteric fat pad around the SMA and behind the AA has been mentioned in the literature as the most common cause of SMA syndrome secondary to excessive weight loss for any reason like eating disorders, malabsorption, gastric bypass surgery, trauma, malignancies and inflammatory bowel disease (Crohn’s disease or ulcerative colitis). People who had extensive burns can develop SMA syndrome due to fat and muscle wasting seen in this injury.CT angiography or MRI can measure the angle between the AA and the SMA. The normal angle is 25 – 60 degrees while with SMA syndrome is reduced to 7 – 22 degrees. The distance between the AA and the SMA is normally 10 – 28 mm but with SMA syndrome it is reduced to 2 to 8 mm. Some people with SMA syndrome may be born with this abnormality and diagnosed as infants or preteen children. The ligament of Treitz is a structure that suspends the junction between the duodenum and the jejunum. A lower origin of the SMA from the AA can be a factor. The ligament of Treitz can be short or thick causing an acute angulation. A linear growth spurt without accompanying increase in abdominal girth can be a predisposing factor. Patients who had surgical correction for scoliosis can develop SMA syndrome because the angle or the distance between the AA and SMA can decrease when the spine is straightened causing stretching of the AA. Patients who were placed in a body cast after injury or spine surgery have developed SMA syndrome hence the term cast syndrome.There have been siblings reported to have SMA syndrome.
|
Causes of Superior Mesenteric Artery Syndrome. SMA syndrome occurs when the duodenum is compressed by the SMA against the AA to cause blockage and prevent progression of food or fluids into the rest of the small intestine. The small intestine is a long, winding tube that connects the stomach to the large intestine ending in the anus. The small intestine is divided into three sections – duodenum, jejunum and ileum. Each section has a role in digestion and absorption of nutrients that were previously digested in the stomach. The duodenum is the first part of the small intestine and directly connects to the stomach. It has four parts or sections. The third section can be compressed by the SMA against the AA causing a partial obstruction which manifests as nausea, vomiting and epigastric pain. The mesentery is a double fold that suspends the small intestine and large intestine from the posterior abdominal wall. Loss of the mesenteric fat pad around the SMA and behind the AA has been mentioned in the literature as the most common cause of SMA syndrome secondary to excessive weight loss for any reason like eating disorders, malabsorption, gastric bypass surgery, trauma, malignancies and inflammatory bowel disease (Crohn’s disease or ulcerative colitis). People who had extensive burns can develop SMA syndrome due to fat and muscle wasting seen in this injury.CT angiography or MRI can measure the angle between the AA and the SMA. The normal angle is 25 – 60 degrees while with SMA syndrome is reduced to 7 – 22 degrees. The distance between the AA and the SMA is normally 10 – 28 mm but with SMA syndrome it is reduced to 2 to 8 mm. Some people with SMA syndrome may be born with this abnormality and diagnosed as infants or preteen children. The ligament of Treitz is a structure that suspends the junction between the duodenum and the jejunum. A lower origin of the SMA from the AA can be a factor. The ligament of Treitz can be short or thick causing an acute angulation. A linear growth spurt without accompanying increase in abdominal girth can be a predisposing factor. Patients who had surgical correction for scoliosis can develop SMA syndrome because the angle or the distance between the AA and SMA can decrease when the spine is straightened causing stretching of the AA. Patients who were placed in a body cast after injury or spine surgery have developed SMA syndrome hence the term cast syndrome.There have been siblings reported to have SMA syndrome.
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1174_3
|
Affects of Superior Mesenteric Artery Syndrome
|
The prevalence (the number of people with a disease or disorder in a given population at a given time) is unknown. The most frequently quoted estimate is that 0.13 to 0.3% of people in the United States general population have this disorder. SMA syndrome has been reported in greater frequency among teenagers and young adults but can occur at any age including infants and the elderly. It seems to affect more women than men by 3:2 ratio. SMA syndrome can affect individuals of any racial or ethnic heritage hence it is worldwide. It is likely that some people with SMA syndrome have not been diagnosed so the true prevalence may be higher than reported.
|
Affects of Superior Mesenteric Artery Syndrome. The prevalence (the number of people with a disease or disorder in a given population at a given time) is unknown. The most frequently quoted estimate is that 0.13 to 0.3% of people in the United States general population have this disorder. SMA syndrome has been reported in greater frequency among teenagers and young adults but can occur at any age including infants and the elderly. It seems to affect more women than men by 3:2 ratio. SMA syndrome can affect individuals of any racial or ethnic heritage hence it is worldwide. It is likely that some people with SMA syndrome have not been diagnosed so the true prevalence may be higher than reported.
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1174_4
|
Related disorders of Superior Mesenteric Artery Syndrome
|
There are many conditions that can cause signs and symptoms similar to SMA syndrome like peptic ulcer disease, gall bladder disease (gallstone disease or dysfunction known as biliary dyskinesia) irritable bowel disease, inflammation of the duodenum (duodenitis), visceral neuropathy, cyclic vomiting syndrome and inflammation of the pancreas (pancreatitis). Disorders that cause duodenal dysmotility including diabetes, vascular collagen disorder and chronic mesenteric ischemia can also resemble SMA syndrome. Median arcuate ligament syndrome (MALS) or celiac steal syndrome can mimic SMA syndrome.Gastroparesis can be seen in chronic SMA syndrome. This is defined as delayed gastric emptying without anatomic obstruction of the flow from the stomach to the duodenum. Gastroparesis can occur as a disease entity after an acute viral illness in children and in women with diabetes. For most people with gastroparesis, the cause is unknown. (For more information on this disorder, choose “gastroparesis” as your search term in the Rare Disorder Database).
|
Related disorders of Superior Mesenteric Artery Syndrome. There are many conditions that can cause signs and symptoms similar to SMA syndrome like peptic ulcer disease, gall bladder disease (gallstone disease or dysfunction known as biliary dyskinesia) irritable bowel disease, inflammation of the duodenum (duodenitis), visceral neuropathy, cyclic vomiting syndrome and inflammation of the pancreas (pancreatitis). Disorders that cause duodenal dysmotility including diabetes, vascular collagen disorder and chronic mesenteric ischemia can also resemble SMA syndrome. Median arcuate ligament syndrome (MALS) or celiac steal syndrome can mimic SMA syndrome.Gastroparesis can be seen in chronic SMA syndrome. This is defined as delayed gastric emptying without anatomic obstruction of the flow from the stomach to the duodenum. Gastroparesis can occur as a disease entity after an acute viral illness in children and in women with diabetes. For most people with gastroparesis, the cause is unknown. (For more information on this disorder, choose “gastroparesis” as your search term in the Rare Disorder Database).
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1174_5
|
Diagnosis of Superior Mesenteric Artery Syndrome
|
A diagnosis of SMA syndrome is based on the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A team approach to diagnosis is essential and may include a primary care physician (pediatrician, internist or general practitioner), gastroenterologist, surgeon (pediatric or general), radiologist, nutritionist or dietician, pain specialist, and psychologist or psychiatrist. It is a diagnosis of exclusion hence a period of observation and trial of therapy may be required before a definitive diagnosis is made. Delay in the diagnosis and treatment worsens the condition and can lead to a fatal outcome.Clinical testing and WorkupA plain radiograph of the abdomen (x-ray) is non-specific or may show an enlarged stomach or bloating. Computed tomography angiography (CTA) or CT scan with intravenous contrast will show the angulation and distance between the AA and SMA as discussed previously. Any radiographic findings must be correlated with the clinical symptoms and response to treatment to be considered important. MRI can be used for patients who are allergic to the IV contrast and will show the same findings. Hypotonic duodenography was used as the main test for diagnosis prior to CTA. Barium is ingested or injected to the stomach via a tube with fluoroscopy to follow the movement of the barium into the small intestine. If there is delay in gastric emptying, the contrast will remain in the stomach for as long as 6 hours. If there is no delay in gastric emptying, it empties into the duodenum and then to the jejunum without delay. If the patient has SMA syndrome, there will be dilation of the first and second portion of the duodenum and a “to and fro” motion of the contrast in that area. There will be an abrupt cutoff of contrast at the third portion of the duodenum corresponding to the compression of the SMA against the duodenum. When the patient lays on the right side or face down, the contrast will flow into the jejunum. This can be duplicated with a CT scan with oral contrast.A test called a Doppler ultrasound can be used in the diagnosis of SMA syndrome but is not as sensitive as CTA and is operator dependent. This is more important when there is a suspicion of an associated median arcuate ligament syndrome (MALS) since it can detect the differential velocity of the celiac artery flow during respiration i.e. narrowing occurs during expiration.
|
Diagnosis of Superior Mesenteric Artery Syndrome. A diagnosis of SMA syndrome is based on the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A team approach to diagnosis is essential and may include a primary care physician (pediatrician, internist or general practitioner), gastroenterologist, surgeon (pediatric or general), radiologist, nutritionist or dietician, pain specialist, and psychologist or psychiatrist. It is a diagnosis of exclusion hence a period of observation and trial of therapy may be required before a definitive diagnosis is made. Delay in the diagnosis and treatment worsens the condition and can lead to a fatal outcome.Clinical testing and WorkupA plain radiograph of the abdomen (x-ray) is non-specific or may show an enlarged stomach or bloating. Computed tomography angiography (CTA) or CT scan with intravenous contrast will show the angulation and distance between the AA and SMA as discussed previously. Any radiographic findings must be correlated with the clinical symptoms and response to treatment to be considered important. MRI can be used for patients who are allergic to the IV contrast and will show the same findings. Hypotonic duodenography was used as the main test for diagnosis prior to CTA. Barium is ingested or injected to the stomach via a tube with fluoroscopy to follow the movement of the barium into the small intestine. If there is delay in gastric emptying, the contrast will remain in the stomach for as long as 6 hours. If there is no delay in gastric emptying, it empties into the duodenum and then to the jejunum without delay. If the patient has SMA syndrome, there will be dilation of the first and second portion of the duodenum and a “to and fro” motion of the contrast in that area. There will be an abrupt cutoff of contrast at the third portion of the duodenum corresponding to the compression of the SMA against the duodenum. When the patient lays on the right side or face down, the contrast will flow into the jejunum. This can be duplicated with a CT scan with oral contrast.A test called a Doppler ultrasound can be used in the diagnosis of SMA syndrome but is not as sensitive as CTA and is operator dependent. This is more important when there is a suspicion of an associated median arcuate ligament syndrome (MALS) since it can detect the differential velocity of the celiac artery flow during respiration i.e. narrowing occurs during expiration.
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1174_6
|
Therapies of Superior Mesenteric Artery Syndrome
|
TreatmentThe treatment of SMA syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of providers including a pediatrician, internist, gastroenterologist, surgeon (pediatric or general), nutritionist or dietician, pain therapist, psychologist, or psychiatrist. Psychosocial support of the entire family may be needed.Conservative therapy should be tried first before surgery is considered. Frequent small feedings with supplemental high calorie liquid followed by postural therapy are tried first. Insertion of a tube from the nose to the jejunum (naso-jejunal tube) is next. Special formula is used for feeding delivered via a pump for 16 to 20 hours that will deliver adequate calories and fluids needed by the patient. If these methods of feeding fail, high calorie IV feeding (total parenteral nutrition – TPN) maybe needed initially and can supplement tube feedings. Weight gain is the goal to restore the mesenteric fat pad and reverse the loss of angle and decrease the distance between the AA and SMA. If conservative measures are not working within 6 to 8 weeks and the symptoms worsen, especially if the patient has severe pain and is unable to tolerate GI feeding, surgery becomes indicated.Gastro-jejunostomy is a procedure where a loop of jejunum is connected to the stomach, but because it is fraught with problems is no longer recommended.Duodeno-jejunostomy is a procedure where a loop of jejunum is connected to the second portion of the duodenum bypassing the area of obstruction (third portion of duodenum). This can be performed with a small incision (laparoscopically) or with open surgery. This is the most frequently used procedure to relieve the blockage and has a success rate of 70 to 90% according to the literature. Some patients will continue to have pain and symptoms after this procedure.The Strong procedure divides the ligament of Treitz to allow lowering of the duodeno-jejunal junction which can relieve the compression. If the duodeno-jejunal junction is not sutured to the right abdominal wall, recurrence of the SMA syndrome occurs.
Duodenal derotation is a procedure where the ligament of Treitz is divided and the duodeno-jejunal junction (DJ) is rotated away from the SMA and sutured to the right abdominal wall. If there is a severe kink at the DJ a side-to-side duodeno-jejunostomy is performed at that site. This is a physiologic connection between the duodenum and jejunum and will not have long term complications.The other procedure is known as infrarenal transposition of the SMA where the SMA is disconnected from the AA and reattached again below the left renal vein and the third portion of the duodenum. This eliminates the compression factor of the SMA.
|
Therapies of Superior Mesenteric Artery Syndrome. TreatmentThe treatment of SMA syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of providers including a pediatrician, internist, gastroenterologist, surgeon (pediatric or general), nutritionist or dietician, pain therapist, psychologist, or psychiatrist. Psychosocial support of the entire family may be needed.Conservative therapy should be tried first before surgery is considered. Frequent small feedings with supplemental high calorie liquid followed by postural therapy are tried first. Insertion of a tube from the nose to the jejunum (naso-jejunal tube) is next. Special formula is used for feeding delivered via a pump for 16 to 20 hours that will deliver adequate calories and fluids needed by the patient. If these methods of feeding fail, high calorie IV feeding (total parenteral nutrition – TPN) maybe needed initially and can supplement tube feedings. Weight gain is the goal to restore the mesenteric fat pad and reverse the loss of angle and decrease the distance between the AA and SMA. If conservative measures are not working within 6 to 8 weeks and the symptoms worsen, especially if the patient has severe pain and is unable to tolerate GI feeding, surgery becomes indicated.Gastro-jejunostomy is a procedure where a loop of jejunum is connected to the stomach, but because it is fraught with problems is no longer recommended.Duodeno-jejunostomy is a procedure where a loop of jejunum is connected to the second portion of the duodenum bypassing the area of obstruction (third portion of duodenum). This can be performed with a small incision (laparoscopically) or with open surgery. This is the most frequently used procedure to relieve the blockage and has a success rate of 70 to 90% according to the literature. Some patients will continue to have pain and symptoms after this procedure.The Strong procedure divides the ligament of Treitz to allow lowering of the duodeno-jejunal junction which can relieve the compression. If the duodeno-jejunal junction is not sutured to the right abdominal wall, recurrence of the SMA syndrome occurs.
Duodenal derotation is a procedure where the ligament of Treitz is divided and the duodeno-jejunal junction (DJ) is rotated away from the SMA and sutured to the right abdominal wall. If there is a severe kink at the DJ a side-to-side duodeno-jejunostomy is performed at that site. This is a physiologic connection between the duodenum and jejunum and will not have long term complications.The other procedure is known as infrarenal transposition of the SMA where the SMA is disconnected from the AA and reattached again below the left renal vein and the third portion of the duodenum. This eliminates the compression factor of the SMA.
| 1,174 |
Superior Mesenteric Artery Syndrome
|
nord_1175_0
|
Overview of Superior Semicircular Canal Dehiscence
|
Superior semicircular canal dehiscence (SSCD) has been defined as the absence of bone overlying the superior semicircular canal facing toward the dura of the middle cranial fossa. SSCD has been implicated as the cause of a variety of inner ear symptoms including Tullio’s phenomenon, pressure induced vertigo, aural fullness, autophony, conductive hearing loss and fluctuating or progressive sensorineural hearing loss. SSCD has also been reported to be asymptomatic in some people. In the past, many patients with SSCD were misdiagnosed as having otosclerosis, patulous eustachian tubes, middle ear perilymphatic fistulas or Ménière’s disease. Identification of this condition requires a high degree of suspicion, appropriate findings on physical exam, lab testing and confirmation on high-resolution CT scan. Surgical repair of the SSCD or occlusion of the superior canal has been reported with a high degree of symptom resolution.
|
Overview of Superior Semicircular Canal Dehiscence. Superior semicircular canal dehiscence (SSCD) has been defined as the absence of bone overlying the superior semicircular canal facing toward the dura of the middle cranial fossa. SSCD has been implicated as the cause of a variety of inner ear symptoms including Tullio’s phenomenon, pressure induced vertigo, aural fullness, autophony, conductive hearing loss and fluctuating or progressive sensorineural hearing loss. SSCD has also been reported to be asymptomatic in some people. In the past, many patients with SSCD were misdiagnosed as having otosclerosis, patulous eustachian tubes, middle ear perilymphatic fistulas or Ménière’s disease. Identification of this condition requires a high degree of suspicion, appropriate findings on physical exam, lab testing and confirmation on high-resolution CT scan. Surgical repair of the SSCD or occlusion of the superior canal has been reported with a high degree of symptom resolution.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1175_1
|
Symptoms of Superior Semicircular Canal Dehiscence
|
SSCD has been labelled the “great otologic mimicker” because it can simulate the symptoms of so many other ear disorders. However, the most common symptoms are vertigo/dizziness elicited by pressure altering activity, Tullio’s phenomenon (sound-induced vertigo), fullness/pressure in the ear and autophony. Autophony is hearing internal noises louder than would be expected, such as hearing your eyes move/blink, heartbeat or joint movements. Hearing loss and fluctuating hearing loss can occur, mimicking otosclerosis or Meniere’s disease. Fullness in the ear and hearing your breathing loudly in the ear are symptoms of patulous eustachian tube but can also be found with SSCD. Finally, most patients with the anatomic defect of superior semicircular canal dehiscence have no symptoms at all for some time prior to developing symptoms.
|
Symptoms of Superior Semicircular Canal Dehiscence. SSCD has been labelled the “great otologic mimicker” because it can simulate the symptoms of so many other ear disorders. However, the most common symptoms are vertigo/dizziness elicited by pressure altering activity, Tullio’s phenomenon (sound-induced vertigo), fullness/pressure in the ear and autophony. Autophony is hearing internal noises louder than would be expected, such as hearing your eyes move/blink, heartbeat or joint movements. Hearing loss and fluctuating hearing loss can occur, mimicking otosclerosis or Meniere’s disease. Fullness in the ear and hearing your breathing loudly in the ear are symptoms of patulous eustachian tube but can also be found with SSCD. Finally, most patients with the anatomic defect of superior semicircular canal dehiscence have no symptoms at all for some time prior to developing symptoms.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1175_2
|
Causes of Superior Semicircular Canal Dehiscence
|
The anatomic defect of SSCD is believed to be a developmental anomaly of the temporal bone in the vast majority of cases. At birth, the bone over the top of the inner ear, which is the floor of the middle cranial fossa, is very thin or absent. Over the first three years of life, this bone thickens considerably. However, this is variable and approximately 20% of the population is left with holes in the middle fossa floor that extend into the middle ear or mastoid. These are typically free of any symptoms unless intracranial pressure causes the brain to prolapse through one of these holes – an event typically not seen until the latter decades of life. Approximately 1-2% of the population will be left with a defect of the bone over the superior semicircular canal resulting in SSCD. However, this usually does not cause symptoms until later in life.A second event occurs in the vast majority of patients prior to the onset of symptoms. This second event is most commonly head trauma or a major pressure-altering event such as scuba diving, air travel or straining. For many patients, it is uncertain why the symptoms started.There is also evidence of gradual thinning of the temporal bone over the superior semicircular canal throughout life. This thinning is an extremely slow process, but it does present another possibility for SSCD development. Theoretically, if someone has thin bone over the SSC, over time the bone could dissolve away. This could set up the environment for SSCD.Much less common are erosive processes that can cause the development of SSCD. This can be seen with benign or malignant tumors and with arachnoid granulations. Lastly, trauma can also result in fractures across the SSC that can produce SSCD.
|
Causes of Superior Semicircular Canal Dehiscence. The anatomic defect of SSCD is believed to be a developmental anomaly of the temporal bone in the vast majority of cases. At birth, the bone over the top of the inner ear, which is the floor of the middle cranial fossa, is very thin or absent. Over the first three years of life, this bone thickens considerably. However, this is variable and approximately 20% of the population is left with holes in the middle fossa floor that extend into the middle ear or mastoid. These are typically free of any symptoms unless intracranial pressure causes the brain to prolapse through one of these holes – an event typically not seen until the latter decades of life. Approximately 1-2% of the population will be left with a defect of the bone over the superior semicircular canal resulting in SSCD. However, this usually does not cause symptoms until later in life.A second event occurs in the vast majority of patients prior to the onset of symptoms. This second event is most commonly head trauma or a major pressure-altering event such as scuba diving, air travel or straining. For many patients, it is uncertain why the symptoms started.There is also evidence of gradual thinning of the temporal bone over the superior semicircular canal throughout life. This thinning is an extremely slow process, but it does present another possibility for SSCD development. Theoretically, if someone has thin bone over the SSC, over time the bone could dissolve away. This could set up the environment for SSCD.Much less common are erosive processes that can cause the development of SSCD. This can be seen with benign or malignant tumors and with arachnoid granulations. Lastly, trauma can also result in fractures across the SSC that can produce SSCD.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1175_3
|
Affects of Superior Semicircular Canal Dehiscence
|
SSCD can affect all age groups. There are no studies looking at the demographics of SSCD, however, the vast majority of patients diagnosed with SSCD are adults. Although the incidence of finding SSCD on a scan is the same for adults and children, the incidence of symptomatic SSCD in children is much lower.
|
Affects of Superior Semicircular Canal Dehiscence. SSCD can affect all age groups. There are no studies looking at the demographics of SSCD, however, the vast majority of patients diagnosed with SSCD are adults. Although the incidence of finding SSCD on a scan is the same for adults and children, the incidence of symptomatic SSCD in children is much lower.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1175_4
|
Related disorders of Superior Semicircular Canal Dehiscence
|
Dehiscence of bone in other parts of the otic capsule can produce similar syndromes, although they are much less common. Other locations include the posterior semicircular canal, the horizontal semicircular canal and cochlea. Posterior semicircular canal dehiscence is often due to a high riding jugular bulb but can also been seen with anomalies of the vestibular aqueduct, such as enlarged vestibular aqueduct syndrome (EVAS). EVAS, by itself can also produce symptoms similar to SSCD. Horizontal semicircular canal dehiscence is most frequently the result of an eroding process such as cholesteatoma. The cochlea can have bony dehiscence where it abuts the carotid artery and at the labyrinthine segment of the facial nerve. Lastly, the bony opening where the hearing nerve enters the cochlea (at the internal auditory canal) can be abnormally wide, resulting in symptoms similar to SSCD.An additional confusing factor involved in the diagnosis of SSCD is the entity referred to as near dehiscence. In this condition, the bone overlying the superior semicircular canal can be intact but be so thin as to allow transmission of pressure waves to the inner ear provoking SSCD symptoms. The critical measurement appears to be <0.5 mm thickness. It has been shown to be amenable to surgical treatment. However, this must be supported by the patient’s history and objective testing to confirm the suspicion.
|
Related disorders of Superior Semicircular Canal Dehiscence. Dehiscence of bone in other parts of the otic capsule can produce similar syndromes, although they are much less common. Other locations include the posterior semicircular canal, the horizontal semicircular canal and cochlea. Posterior semicircular canal dehiscence is often due to a high riding jugular bulb but can also been seen with anomalies of the vestibular aqueduct, such as enlarged vestibular aqueduct syndrome (EVAS). EVAS, by itself can also produce symptoms similar to SSCD. Horizontal semicircular canal dehiscence is most frequently the result of an eroding process such as cholesteatoma. The cochlea can have bony dehiscence where it abuts the carotid artery and at the labyrinthine segment of the facial nerve. Lastly, the bony opening where the hearing nerve enters the cochlea (at the internal auditory canal) can be abnormally wide, resulting in symptoms similar to SSCD.An additional confusing factor involved in the diagnosis of SSCD is the entity referred to as near dehiscence. In this condition, the bone overlying the superior semicircular canal can be intact but be so thin as to allow transmission of pressure waves to the inner ear provoking SSCD symptoms. The critical measurement appears to be <0.5 mm thickness. It has been shown to be amenable to surgical treatment. However, this must be supported by the patient’s history and objective testing to confirm the suspicion.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1175_5
|
Diagnosis of Superior Semicircular Canal Dehiscence
|
There are three essential elements to make the diagnosis of SSCD:As mentioned earlier, there are many patients who have the anatomic defect of SSCD but have no symptoms at all. These patients do not have SSCD syndrome and should not be treated but observed. They may or may not develop symptoms later in life. However, if someone has the symptoms of SSCD, the next step is physiologic testing. Several findings on physiologic tests that can be suggestive of SSCD include:If the above two criteria are met, then a high resolution thin-sliced CT scan of the temporal bone is ordered. The slice thickness should be as thin as possible (<0.6mm, but preferably 0.125 mm). The orientation of the slices should be done in the axial, coronal, Stenvers and Poschl planes. Identification of a dehiscence on a CT scan with thicker slices could easily not be a true dehiscence, but the result of averaging artifact. Once these three elements are met, the diagnosis of SSCD can be confirmed. However, it should be noted that patients with SSCD can also have other dehiscences of the otic capsule. The otic capsule in SSCD patients is of less volume than the norm which may explain this phenomenon. There is also a higher incidence of Arnold Chiari malformation among SSCD patients.Third mobile window disorders (TMWD) are defined as a group of disorders, among which superior semicircular canal dehiscence syndrome is the most recognized. They have a common clinical presentation including a combination of Tullio's phenomenon, pressure/strain-induced vertigo and/or autophony, but there are certainly other associated symptoms. The “third window” effect results from the altered inner ear mechanics due to a defect in the inner ear or an aberration of its structural integrity. Initially thought of as rare when the first paper was published in 1998, TMWD are in fact very much more common than realized and it is important to be aware of this. If doctors elicit a full medical history from their patients, including any head trauma, otic barotrauma resulting from air travel etc, the chance of a wrong diagnosis will be greatly reduced. The superior canal may have a complete bony coverage but one of the lesser recognised TMWD must not be overlooked.The John Hopkins temporal bone histology study of more than 1,000 temporal bones demonstrated 0.5% incidence of SSCD, and about 1.5% incidence of extreme bony thinning. Cochlear-facial dehiscence is actually more common than SSCD, although not recognized or diagnosed nearly as frequently, and their combined incidence is 1.1% in the general population.
|
Diagnosis of Superior Semicircular Canal Dehiscence. There are three essential elements to make the diagnosis of SSCD:As mentioned earlier, there are many patients who have the anatomic defect of SSCD but have no symptoms at all. These patients do not have SSCD syndrome and should not be treated but observed. They may or may not develop symptoms later in life. However, if someone has the symptoms of SSCD, the next step is physiologic testing. Several findings on physiologic tests that can be suggestive of SSCD include:If the above two criteria are met, then a high resolution thin-sliced CT scan of the temporal bone is ordered. The slice thickness should be as thin as possible (<0.6mm, but preferably 0.125 mm). The orientation of the slices should be done in the axial, coronal, Stenvers and Poschl planes. Identification of a dehiscence on a CT scan with thicker slices could easily not be a true dehiscence, but the result of averaging artifact. Once these three elements are met, the diagnosis of SSCD can be confirmed. However, it should be noted that patients with SSCD can also have other dehiscences of the otic capsule. The otic capsule in SSCD patients is of less volume than the norm which may explain this phenomenon. There is also a higher incidence of Arnold Chiari malformation among SSCD patients.Third mobile window disorders (TMWD) are defined as a group of disorders, among which superior semicircular canal dehiscence syndrome is the most recognized. They have a common clinical presentation including a combination of Tullio's phenomenon, pressure/strain-induced vertigo and/or autophony, but there are certainly other associated symptoms. The “third window” effect results from the altered inner ear mechanics due to a defect in the inner ear or an aberration of its structural integrity. Initially thought of as rare when the first paper was published in 1998, TMWD are in fact very much more common than realized and it is important to be aware of this. If doctors elicit a full medical history from their patients, including any head trauma, otic barotrauma resulting from air travel etc, the chance of a wrong diagnosis will be greatly reduced. The superior canal may have a complete bony coverage but one of the lesser recognised TMWD must not be overlooked.The John Hopkins temporal bone histology study of more than 1,000 temporal bones demonstrated 0.5% incidence of SSCD, and about 1.5% incidence of extreme bony thinning. Cochlear-facial dehiscence is actually more common than SSCD, although not recognized or diagnosed nearly as frequently, and their combined incidence is 1.1% in the general population.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1175_6
|
Therapies of Superior Semicircular Canal Dehiscence
|
Because the condition of SSCD is still fairly new (identified in 1998), it could be argued that all treatments are considered experimental or investigational. However, the most frequently employed are surgical. Surgery for SSCD has included resurfacing the defect with a variety of materials, plugging the superior semicircular canal and a combination of resurfacing and plugging. These techniques can be done through a transmastoid or a middle fossa craniotomy approach. These techniques have found great success in reducing or eliminating the vestibular symptoms of SSCD. These techniques are also effective in reducing or eliminating autophony but they have not been effective in improving hearing. A lesser approach that seems to give similar benefits is reinforcement of the middle ear windows. This surgery has the advantage of being a more minimally invasive procedure, but the success rate seems to be much lower with a higher recurrence rate in the long term.
|
Therapies of Superior Semicircular Canal Dehiscence. Because the condition of SSCD is still fairly new (identified in 1998), it could be argued that all treatments are considered experimental or investigational. However, the most frequently employed are surgical. Surgery for SSCD has included resurfacing the defect with a variety of materials, plugging the superior semicircular canal and a combination of resurfacing and plugging. These techniques can be done through a transmastoid or a middle fossa craniotomy approach. These techniques have found great success in reducing or eliminating the vestibular symptoms of SSCD. These techniques are also effective in reducing or eliminating autophony but they have not been effective in improving hearing. A lesser approach that seems to give similar benefits is reinforcement of the middle ear windows. This surgery has the advantage of being a more minimally invasive procedure, but the success rate seems to be much lower with a higher recurrence rate in the long term.
| 1,175 |
Superior Semicircular Canal Dehiscence
|
nord_1176_0
|
Overview of Susac Syndrome
|
SummarySusac syndrome is a relatively rare disorder characterized by three main problems: impaired brain function (encephalopathy), partial or complete blockage (occlusion) of the small arteries and capillaries that supply blood to the retina (branch retinal artery occlusion, or BRAO) and inner ear disease (hearing loss, most notably). MRI of the brain typically reveals “snowball” lesions in the corpus callosum. Three main forms of Susac syndrome have become apparent. In one form, encephalopathy is the main problem. In the second form, BRAO and hearing loss are the main problems and there is little or no brain disease. In the third form, encephalopathy is the main problem in the beginning, but recurrent episodes of BRAO become the main problem after the encephalopathy subsides. The encephalopathic form of Susac syndrome often resolves within 1-3 years. The other forms tend to follow a more prolonged, more chronic or more recurrent course (for 3-10 years or more). All forms require immunosuppressive treatment while the disease is active.IntroductionAlthough considered rare, Susac syndrome is being recognized more often worldwide and its true frequency in the general population is unknown. This is because the disorder may be misdiagnosed, often as “atypical” multiple sclerosis.Susac syndrome is an autoimmune disease—specifically, an autoimmune endotheliopathy. “Autoimmune” means that a person’s own immune system is mistakenly attacking its own tissue. An “endotheliopathy” is any disorder that involves injury to the endothelium, which is the thin layer of cells that line the inner walls of blood vessels. In Susac syndrome, the person’s own immune system is mistakenly attacking the endothelial lining of the smallest blood vessels (the capillaries, venules and arterioles) in the brain, retina and inner ear. When the endothelial cells become injured, they tend to swell, and this endothelial cell swelling plays a key role in the partial or complete occlusion (blockage) of the tiny vessels in the brain, retina and inner ear. This blockage results in decreased blood flow through the vessels and, therefore, decreased delivery of oxygen and nutrients to the brain, retina and inner ear—causing either temporary dysfunction or permanent damage to these three organs, depending on the severity and duration of the decreased blood flow.
|
Overview of Susac Syndrome. SummarySusac syndrome is a relatively rare disorder characterized by three main problems: impaired brain function (encephalopathy), partial or complete blockage (occlusion) of the small arteries and capillaries that supply blood to the retina (branch retinal artery occlusion, or BRAO) and inner ear disease (hearing loss, most notably). MRI of the brain typically reveals “snowball” lesions in the corpus callosum. Three main forms of Susac syndrome have become apparent. In one form, encephalopathy is the main problem. In the second form, BRAO and hearing loss are the main problems and there is little or no brain disease. In the third form, encephalopathy is the main problem in the beginning, but recurrent episodes of BRAO become the main problem after the encephalopathy subsides. The encephalopathic form of Susac syndrome often resolves within 1-3 years. The other forms tend to follow a more prolonged, more chronic or more recurrent course (for 3-10 years or more). All forms require immunosuppressive treatment while the disease is active.IntroductionAlthough considered rare, Susac syndrome is being recognized more often worldwide and its true frequency in the general population is unknown. This is because the disorder may be misdiagnosed, often as “atypical” multiple sclerosis.Susac syndrome is an autoimmune disease—specifically, an autoimmune endotheliopathy. “Autoimmune” means that a person’s own immune system is mistakenly attacking its own tissue. An “endotheliopathy” is any disorder that involves injury to the endothelium, which is the thin layer of cells that line the inner walls of blood vessels. In Susac syndrome, the person’s own immune system is mistakenly attacking the endothelial lining of the smallest blood vessels (the capillaries, venules and arterioles) in the brain, retina and inner ear. When the endothelial cells become injured, they tend to swell, and this endothelial cell swelling plays a key role in the partial or complete occlusion (blockage) of the tiny vessels in the brain, retina and inner ear. This blockage results in decreased blood flow through the vessels and, therefore, decreased delivery of oxygen and nutrients to the brain, retina and inner ear—causing either temporary dysfunction or permanent damage to these three organs, depending on the severity and duration of the decreased blood flow.
| 1,176 |
Susac Syndrome
|
nord_1176_1
|
Symptoms of Susac Syndrome
|
The specific symptoms, severity, and outcome of Susac syndrome vary from one person to another. Commonly, the three main features (encephalopathy, branch retinal arterial occlusions and hearing loss) are not all present at disease onset, and all three do not necessarily develop in all patients. When patients are first evaluated by a physician, any one of the three main features may be the only feature present, with one or both of the other features appearing only later. The skin may also be involved, and the symptoms may include livedo reticularis and a diffuse micropapular rash.In many patients, headaches (including migraine-like headaches) precede the development of other symptoms of Susac syndrome. A variety of additional neurological findings may develop: cognitive dysfunction (including memory loss, confusion and decreased executive function), gait disturbance and slurred speech (dysarthria). Some individuals develop psychiatric symptoms such as paranoia or personality or behavioral changes. The specific neurological symptoms that develop will vary from one person to another.Branch retinal artery occlusion (BRAO) can cause the patient to notice a “dark spot” or “black area” in their field of vision; or some patients describe a “curtain or shade being drawn” over a portion of their vision. The medical term for these symptoms is “scotoma.” These symptoms are due to injury to the retina, because of blocked blood flow. The retina is the thin layer of nerve cells that sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. Both eyes can be affected in individuals with Susac syndrome. Permanent impairment of vision may occur. BRAOs may occur early in some individuals or later in the course of the disease in others.Many individuals with Susac syndrome develop hearing loss due to damage to the small, snail-shaped organ of the inner ear known as the cochlea. The cochlea converts sound into nerve impulses to be sent to the brain. The damage to the cochlea is caused by the blockage of blood flow through the small vessels that supply blood to the cochlea. Hearing loss in Susac syndrome is primarily at low frequencies and usually occurs relatively suddenly. It may affect both ears (bilateral). Its severity can range from mild to severe. In severe cases, cochlear implantation is warranted. In some cases, hearing loss may occur before other symptoms of Susac syndrome develop. Hearing loss is often accompanied by intense ringing of the ears (tinnitus). The vestibular apparatus, which is also located in the inner ear, can also be affected by the microvascular endotheliopathy of Susac syndrome, resulting in vertigo (dizziness).The encephalopathic form of Susac syndrome is typically self-limited (i.e., eventually subsides on its own), but may take a long time to resolve and may recur. It usually runs a course of 1-3 years, during which time individuals may experience fluctuating levels of symptoms (relapsing-remitting). Although the encephalopathic form eventually goes away on its own, treatment is necessary to prevent or minimize damage that can occur while the disease is active. Relapse after a long period of remission is rare but can occur.
|
Symptoms of Susac Syndrome. The specific symptoms, severity, and outcome of Susac syndrome vary from one person to another. Commonly, the three main features (encephalopathy, branch retinal arterial occlusions and hearing loss) are not all present at disease onset, and all three do not necessarily develop in all patients. When patients are first evaluated by a physician, any one of the three main features may be the only feature present, with one or both of the other features appearing only later. The skin may also be involved, and the symptoms may include livedo reticularis and a diffuse micropapular rash.In many patients, headaches (including migraine-like headaches) precede the development of other symptoms of Susac syndrome. A variety of additional neurological findings may develop: cognitive dysfunction (including memory loss, confusion and decreased executive function), gait disturbance and slurred speech (dysarthria). Some individuals develop psychiatric symptoms such as paranoia or personality or behavioral changes. The specific neurological symptoms that develop will vary from one person to another.Branch retinal artery occlusion (BRAO) can cause the patient to notice a “dark spot” or “black area” in their field of vision; or some patients describe a “curtain or shade being drawn” over a portion of their vision. The medical term for these symptoms is “scotoma.” These symptoms are due to injury to the retina, because of blocked blood flow. The retina is the thin layer of nerve cells that sense light and convert it to nerve signals, which are then relayed to the brain through the optic nerve. Both eyes can be affected in individuals with Susac syndrome. Permanent impairment of vision may occur. BRAOs may occur early in some individuals or later in the course of the disease in others.Many individuals with Susac syndrome develop hearing loss due to damage to the small, snail-shaped organ of the inner ear known as the cochlea. The cochlea converts sound into nerve impulses to be sent to the brain. The damage to the cochlea is caused by the blockage of blood flow through the small vessels that supply blood to the cochlea. Hearing loss in Susac syndrome is primarily at low frequencies and usually occurs relatively suddenly. It may affect both ears (bilateral). Its severity can range from mild to severe. In severe cases, cochlear implantation is warranted. In some cases, hearing loss may occur before other symptoms of Susac syndrome develop. Hearing loss is often accompanied by intense ringing of the ears (tinnitus). The vestibular apparatus, which is also located in the inner ear, can also be affected by the microvascular endotheliopathy of Susac syndrome, resulting in vertigo (dizziness).The encephalopathic form of Susac syndrome is typically self-limited (i.e., eventually subsides on its own), but may take a long time to resolve and may recur. It usually runs a course of 1-3 years, during which time individuals may experience fluctuating levels of symptoms (relapsing-remitting). Although the encephalopathic form eventually goes away on its own, treatment is necessary to prevent or minimize damage that can occur while the disease is active. Relapse after a long period of remission is rare but can occur.
| 1,176 |
Susac Syndrome
|
nord_1176_2
|
Causes of Susac Syndrome
|
Susac syndrome is an autoimmune endotheliopathy, a disorder in which the body’s immune system mistakenly attacks the inside lining (endothelium) of the walls of the very tiny blood vessels that supply blood to the brain, retina and inner ear. The exact, underlying reason why this occurs is unknown. Why the microvasculature in the brain, retina, and inner ear are primarily affected is also unclear. The skin may also be involved.
|
Causes of Susac Syndrome. Susac syndrome is an autoimmune endotheliopathy, a disorder in which the body’s immune system mistakenly attacks the inside lining (endothelium) of the walls of the very tiny blood vessels that supply blood to the brain, retina and inner ear. The exact, underlying reason why this occurs is unknown. Why the microvasculature in the brain, retina, and inner ear are primarily affected is also unclear. The skin may also be involved.
| 1,176 |
Susac Syndrome
|
nord_1176_3
|
Affects of Susac Syndrome
|
Susac syndrome primarily affects young women between the ages of 20-40 but has occurred in individuals ranging in age from 9 to 72. Women are affected three times more often than men. Although considered a rare disorder, Susac syndrome is being recognized more often worldwide and may be more common than originally thought. However, because the disorder often goes unrecognized or misdiagnosed, determination of the true frequency of Susac syndrome in the general population has been difficult.So far, Susac syndrome has not been proven to occur more frequently in any particular ethnic group—but early data suggest that it may occur more commonly in Caucasian population groups. It has not been known to occur in more than one member of any family, even when the extended family is considered.Susac syndrome was first reported in the medical literature in 1979 by Dr. John Susac. It has also been referred to as “retinopathy, encephalopathy, deafness associated microangiopathy (RED-M)” or “small infarctions of cochlear, retinal and encephalic tissue (SICRET).”
|
Affects of Susac Syndrome. Susac syndrome primarily affects young women between the ages of 20-40 but has occurred in individuals ranging in age from 9 to 72. Women are affected three times more often than men. Although considered a rare disorder, Susac syndrome is being recognized more often worldwide and may be more common than originally thought. However, because the disorder often goes unrecognized or misdiagnosed, determination of the true frequency of Susac syndrome in the general population has been difficult.So far, Susac syndrome has not been proven to occur more frequently in any particular ethnic group—but early data suggest that it may occur more commonly in Caucasian population groups. It has not been known to occur in more than one member of any family, even when the extended family is considered.Susac syndrome was first reported in the medical literature in 1979 by Dr. John Susac. It has also been referred to as “retinopathy, encephalopathy, deafness associated microangiopathy (RED-M)” or “small infarctions of cochlear, retinal and encephalic tissue (SICRET).”
| 1,176 |
Susac Syndrome
|
nord_1176_4
|
Related disorders of Susac Syndrome
|
The encephalopathic form of Susac syndrome is frequently misdiagnosed as multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). When Susac syndrome presents primarily with hearing loss, tinnitus, and vertigo, it is frequently misdiagnosed as Meniere disease.Multiple sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the covering (myelin sheath) over the nerves. It is a demyelinating disease. The course of this disease is variable; it may advance, relapse, remit or stabilize. The demyelinating plaques or patches scattered throughout the central nervous system interfere with the ability of the nerves to communicate (neurotransmission) and can cause a wide range of neurological symptoms including impairment of speech, numbness or tingling sensation in the limbs and difficulty walking. Dysfunction of the bladder and bowel may also be present. (For more information on this disorder, choose “multiple sclerosis” as your search term in the Rare Disease Database.)Acute disseminated encephalomyelitis (ADEM) is a central nervous system disorder characterized by inflammation of the brain and spinal cord caused by damage to the fatty sheath (myelin) surrounding the nerves. This can occur spontaneously, but usually follows a viral infection or inoculation such as a bacterial or viral vaccine. The symptoms of ADEM usually develop rapidly and may include fever, headaches, vomiting and fatigue. In severe cases, seizures or coma may develop. Vision loss can also occur due to inflammation of the optic nerve.Meniere disease is a disorder that affects the inner ear. Meniere disease is characterized by periodic episodes of vertigo or dizziness; fluctuating, progressive, low-frequency hearing loss; ringing in the ears (tinnitus); and a sensation of fullness or pressure in the ear. The disorder usually affects only one ear. As with Susac syndrome, hearing loss in Meniere disease is caused by damage to the cochlea. The exact cause of Meniere disease is unknown.
|
Related disorders of Susac Syndrome. The encephalopathic form of Susac syndrome is frequently misdiagnosed as multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). When Susac syndrome presents primarily with hearing loss, tinnitus, and vertigo, it is frequently misdiagnosed as Meniere disease.Multiple sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the covering (myelin sheath) over the nerves. It is a demyelinating disease. The course of this disease is variable; it may advance, relapse, remit or stabilize. The demyelinating plaques or patches scattered throughout the central nervous system interfere with the ability of the nerves to communicate (neurotransmission) and can cause a wide range of neurological symptoms including impairment of speech, numbness or tingling sensation in the limbs and difficulty walking. Dysfunction of the bladder and bowel may also be present. (For more information on this disorder, choose “multiple sclerosis” as your search term in the Rare Disease Database.)Acute disseminated encephalomyelitis (ADEM) is a central nervous system disorder characterized by inflammation of the brain and spinal cord caused by damage to the fatty sheath (myelin) surrounding the nerves. This can occur spontaneously, but usually follows a viral infection or inoculation such as a bacterial or viral vaccine. The symptoms of ADEM usually develop rapidly and may include fever, headaches, vomiting and fatigue. In severe cases, seizures or coma may develop. Vision loss can also occur due to inflammation of the optic nerve.Meniere disease is a disorder that affects the inner ear. Meniere disease is characterized by periodic episodes of vertigo or dizziness; fluctuating, progressive, low-frequency hearing loss; ringing in the ears (tinnitus); and a sensation of fullness or pressure in the ear. The disorder usually affects only one ear. As with Susac syndrome, hearing loss in Meniere disease is caused by damage to the cochlea. The exact cause of Meniere disease is unknown.
| 1,176 |
Susac Syndrome
|
nord_1176_5
|
Diagnosis of Susac Syndrome
|
The possibility of Susac syndrome is raised when a patient presents with one or more components of the clinical triad (encephalopathy, BRAO, hearing loss). A diagnosis of definite or probable Susac syndrome is based on the presence of at least two components of the triad and documentation of typical “snowball” lesions in the corpus callosum upon brain MRI. The process of making a diagnosis includes a detailed patient history, a thorough evaluation of all plausible explanations for the illness and a variety of specialized tests including magnetic resonance imaging (MRI), fluorescein angiography and an audiogram.A complete neurological and ophthalmological examination is essential to making the diagnosis of Susac syndrome. The neurological examination may detect symptoms and/or signs of brain dysfunction. The eye examination should include visual field testing to determine whether BRAOs have affected the patient’s vision. Patients often continue to have 20/20 vision even after BRAOs. Pupils should be dilated, and the back of the eye examined carefully. BRAOs should be looked for as well as Gass plaques. Gass plaques appear as small yellow dots in the retinal vessels specifically the arterioles. These Gass plaques are sites of past injury to the endothelium and do not have to be associated at the location of the BRAO.An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues. In individuals with Susac syndrome, an MRI typically shows characteristic changes in the brain, especially in the corpus callosum, which is the structure that connects the right and left halves of the brain. The most characteristic MRI abnormality is presence of lesions (“snowballs,” “spokes” or “holes”) in the central portion of the corpus callosum. These lesions are best seen on sagittal T2 FLAIR images of the corpus callosum.A fluorescein angiogram (FA) is necessary for individuals suspected of having Susac syndrome, even if they do not have eye symptoms. Fluorescein angiography is an eye test that uses a special dye and a camera to evaluate blood flow (circulation) in the retina. In Susac syndrome FA abnormalities include: evidence of partial or complete branch retinal artery occlusion (BRAO); vessel wall hyperfluorescence (increased intensity of dye staining the walls of vessels); “leakage” of dye; and chronic changes out in the periphery (capillary dropout, neovascularization, microaneurysms) with potential for vitreous hemorrhage.Individuals with Susac syndrome should also receive a hearing exam (audiogram) to detect any hearing loss. All patients with suspected Susac syndrome should undergo an audiogram, even if they have not noticed any inner ear symptoms.Adding to the difficulty in making a diagnosis is the fact any one of the components of the clinical triad may be the first and only component present when patients first seek medical attention. This contributes to the probable underreporting of the disorder.
|
Diagnosis of Susac Syndrome. The possibility of Susac syndrome is raised when a patient presents with one or more components of the clinical triad (encephalopathy, BRAO, hearing loss). A diagnosis of definite or probable Susac syndrome is based on the presence of at least two components of the triad and documentation of typical “snowball” lesions in the corpus callosum upon brain MRI. The process of making a diagnosis includes a detailed patient history, a thorough evaluation of all plausible explanations for the illness and a variety of specialized tests including magnetic resonance imaging (MRI), fluorescein angiography and an audiogram.A complete neurological and ophthalmological examination is essential to making the diagnosis of Susac syndrome. The neurological examination may detect symptoms and/or signs of brain dysfunction. The eye examination should include visual field testing to determine whether BRAOs have affected the patient’s vision. Patients often continue to have 20/20 vision even after BRAOs. Pupils should be dilated, and the back of the eye examined carefully. BRAOs should be looked for as well as Gass plaques. Gass plaques appear as small yellow dots in the retinal vessels specifically the arterioles. These Gass plaques are sites of past injury to the endothelium and do not have to be associated at the location of the BRAO.An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues. In individuals with Susac syndrome, an MRI typically shows characteristic changes in the brain, especially in the corpus callosum, which is the structure that connects the right and left halves of the brain. The most characteristic MRI abnormality is presence of lesions (“snowballs,” “spokes” or “holes”) in the central portion of the corpus callosum. These lesions are best seen on sagittal T2 FLAIR images of the corpus callosum.A fluorescein angiogram (FA) is necessary for individuals suspected of having Susac syndrome, even if they do not have eye symptoms. Fluorescein angiography is an eye test that uses a special dye and a camera to evaluate blood flow (circulation) in the retina. In Susac syndrome FA abnormalities include: evidence of partial or complete branch retinal artery occlusion (BRAO); vessel wall hyperfluorescence (increased intensity of dye staining the walls of vessels); “leakage” of dye; and chronic changes out in the periphery (capillary dropout, neovascularization, microaneurysms) with potential for vitreous hemorrhage.Individuals with Susac syndrome should also receive a hearing exam (audiogram) to detect any hearing loss. All patients with suspected Susac syndrome should undergo an audiogram, even if they have not noticed any inner ear symptoms.Adding to the difficulty in making a diagnosis is the fact any one of the components of the clinical triad may be the first and only component present when patients first seek medical attention. This contributes to the probable underreporting of the disorder.
| 1,176 |
Susac Syndrome
|
nord_1176_6
|
Therapies of Susac Syndrome
|
Treatment
Although Susac syndrome can sometimes spontaneously subside, early, appropriately aggressive and appropriately sustained treatment is needed, while the disease is active, to avoid or minimize potential irreversible damage to the brain, retina and inner ear. The two current mainstays of therapy are medications that suppress the activity of the immune system (immunosuppressive agents)—corticosteroid (e.g., prednisone) and intravenous immunoglobulins (IVIG). Additional drugs may also be necessary. Additional drugs that have been used to treat individuals with Susac syndrome include mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab and anti-TNF therapies. Treatment choices depend on the severity of the disease.For individuals with significant hearing loss, a hearing aid may be indicated. For those with profound hearing loss, cochlear implantation may be beneficial.
|
Therapies of Susac Syndrome. Treatment
Although Susac syndrome can sometimes spontaneously subside, early, appropriately aggressive and appropriately sustained treatment is needed, while the disease is active, to avoid or minimize potential irreversible damage to the brain, retina and inner ear. The two current mainstays of therapy are medications that suppress the activity of the immune system (immunosuppressive agents)—corticosteroid (e.g., prednisone) and intravenous immunoglobulins (IVIG). Additional drugs may also be necessary. Additional drugs that have been used to treat individuals with Susac syndrome include mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab and anti-TNF therapies. Treatment choices depend on the severity of the disease.For individuals with significant hearing loss, a hearing aid may be indicated. For those with profound hearing loss, cochlear implantation may be beneficial.
| 1,176 |
Susac Syndrome
|
nord_1177_0
|
Overview of Sutton Disease II
|
Sutton disease II is characterized by the recurring eruption of painful inflamed ulcers in the mouth (stomatitis). There may be multiple ulcers of varying sizes. These ulcers in the mouth are commonly called canker sores. Sutton disease II is also known as recurrent aphthous stomatitis. The exact cause of this disease is not fully understood, although it may be due to an abnormal immune response to the bacteria that are normally in the mouth.
|
Overview of Sutton Disease II. Sutton disease II is characterized by the recurring eruption of painful inflamed ulcers in the mouth (stomatitis). There may be multiple ulcers of varying sizes. These ulcers in the mouth are commonly called canker sores. Sutton disease II is also known as recurrent aphthous stomatitis. The exact cause of this disease is not fully understood, although it may be due to an abnormal immune response to the bacteria that are normally in the mouth.
| 1,177 |
Sutton Disease II
|
nord_1177_1
|
Symptoms of Sutton Disease II
|
The symptoms of Sutton disease II include red, painful ulcers that may appear on the tongue, the lining of the cheeks (buccal mucosa), floor of the mouth, and back of the throat (soft palate). Ulcers may develop in clusters or appear as single lesions scattered throughout the mouth. As many as 15 sores may be present at once. Individuals with Sutton disease II typically experience recurring episodes of mouth sores, usually with 2 to 3 sores during each attack.The ulcers associated with Sutton disease II may vary in size. When the mouth ulcers associated with Sutton disease first erupt, they usually appear as red (inflamed) shallow erosions. Sores less than 1 centimeter in size are considered small or “minor” ulcers. These smaller sores are the most common form of the disease and usually last for 10 to 14 days. Smaller lesions do not usually leave scars. In some cases larger or “major” ulcers may develop lasting for weeks or months. Typically, these larger sores leave scars.In severe cases, other symptoms of Sutton disease II may include a general feeling of weakness (malaise), fever, and swollen lymph nodes around the neck and head (lymphadenopathy).
|
Symptoms of Sutton Disease II. The symptoms of Sutton disease II include red, painful ulcers that may appear on the tongue, the lining of the cheeks (buccal mucosa), floor of the mouth, and back of the throat (soft palate). Ulcers may develop in clusters or appear as single lesions scattered throughout the mouth. As many as 15 sores may be present at once. Individuals with Sutton disease II typically experience recurring episodes of mouth sores, usually with 2 to 3 sores during each attack.The ulcers associated with Sutton disease II may vary in size. When the mouth ulcers associated with Sutton disease first erupt, they usually appear as red (inflamed) shallow erosions. Sores less than 1 centimeter in size are considered small or “minor” ulcers. These smaller sores are the most common form of the disease and usually last for 10 to 14 days. Smaller lesions do not usually leave scars. In some cases larger or “major” ulcers may develop lasting for weeks or months. Typically, these larger sores leave scars.In severe cases, other symptoms of Sutton disease II may include a general feeling of weakness (malaise), fever, and swollen lymph nodes around the neck and head (lymphadenopathy).
| 1,177 |
Sutton Disease II
|
nord_1177_2
|
Causes of Sutton Disease II
|
The exact cause of Sutton disease II is not known. Several studies suggest that it may occur because of an abnormal immune response to the bacteria that are normally present in the mouth. Deficiencies of iron, vitamin B12, and folic acid seem to increase an individual's susceptibility to this disease. Stress and local injury may also be involved. There seems to be no relationship between Sutton disease II and menstruation, pregnancy, and/or menopause, nor is it caused by herpes virus, which is the main cause of common canker sores.
|
Causes of Sutton Disease II. The exact cause of Sutton disease II is not known. Several studies suggest that it may occur because of an abnormal immune response to the bacteria that are normally present in the mouth. Deficiencies of iron, vitamin B12, and folic acid seem to increase an individual's susceptibility to this disease. Stress and local injury may also be involved. There seems to be no relationship between Sutton disease II and menstruation, pregnancy, and/or menopause, nor is it caused by herpes virus, which is the main cause of common canker sores.
| 1,177 |
Sutton Disease II
|
nord_1177_3
|
Affects of Sutton Disease II
|
Sutton disease II affects more adult females than males. However, before puberty, males and females are equally affected. This disease occurs most frequently in malnourished children or adults whose immune systems are suppressed (i.e., by chemotherapy) or compromised (i.e., acquired immune deficiency syndrome).
|
Affects of Sutton Disease II. Sutton disease II affects more adult females than males. However, before puberty, males and females are equally affected. This disease occurs most frequently in malnourished children or adults whose immune systems are suppressed (i.e., by chemotherapy) or compromised (i.e., acquired immune deficiency syndrome).
| 1,177 |
Sutton Disease II
|
nord_1177_4
|
Related disorders of Sutton Disease II
|
Symptoms of the following disorders can be similar to those of Sutton disease II. Comparisons may be useful for a differential diagnosis:Pemphigus is a group of rare autoimmune skin disorders characterized by the development of blisters in the outer layers of the skin and mucous membranes (i.e., in the mouth). The location and type of blisters vary according to the type of pemphigus. Soft (flaccid) blisters typically develop on the skin of the neck, scalp, underarms, and/or mucous membranes. When they occur in the mouth, they may resemble the lesions of Sutton disease II.Herpetic oral ulcers, more commonly known as “canker sores,” are caused by the herpes virus and appear similar to the sores caused by Sutton disease II. They are usually red and painful and typically heal within a few weeks. Unlike the sores of Sutton disease, herpetic oral ulcers usually appear on the gums around the teeth and on the roof of the mouth.Recurrent mouth ulcers may also occur in association with other disorders such as cyclic neutropenia, hand-foot-mouth syndrome, Behcet's syndrome, and iron deficiency disorders. (For more information on these disorders, choose “Neutropenia, Cyclic” and “Behcet's” as your search term in the Rare Disease Database.)
|
Related disorders of Sutton Disease II. Symptoms of the following disorders can be similar to those of Sutton disease II. Comparisons may be useful for a differential diagnosis:Pemphigus is a group of rare autoimmune skin disorders characterized by the development of blisters in the outer layers of the skin and mucous membranes (i.e., in the mouth). The location and type of blisters vary according to the type of pemphigus. Soft (flaccid) blisters typically develop on the skin of the neck, scalp, underarms, and/or mucous membranes. When they occur in the mouth, they may resemble the lesions of Sutton disease II.Herpetic oral ulcers, more commonly known as “canker sores,” are caused by the herpes virus and appear similar to the sores caused by Sutton disease II. They are usually red and painful and typically heal within a few weeks. Unlike the sores of Sutton disease, herpetic oral ulcers usually appear on the gums around the teeth and on the roof of the mouth.Recurrent mouth ulcers may also occur in association with other disorders such as cyclic neutropenia, hand-foot-mouth syndrome, Behcet's syndrome, and iron deficiency disorders. (For more information on these disorders, choose “Neutropenia, Cyclic” and “Behcet's” as your search term in the Rare Disease Database.)
| 1,177 |
Sutton Disease II
|
nord_1177_5
|
Diagnosis of Sutton Disease II
|
Diagnosis of Sutton Disease II.
| 1,177 |
Sutton Disease II
|
|
nord_1177_6
|
Therapies of Sutton Disease II
|
The symptomatic treatment of Sutton disease II involves the application of topical anesthetic (i.e., lidocaine viscous) directly on the affected areas or a thorough mouth rinsing with a special anesthetic solution that helps to reduce irritation and pain. The application of topical steroids may also give symptomatic relief. A dental protective paste (i.e., triamcinolone acetonide or Orabase) may prevent teeth, dental appliances and oral fluids from irritating the ulcers.In severe cases of Sutton disease II, oral and topical steroids may be administered. A mouthrinse that contains the antibiotic tetracycline may also be prescribed to heal painful mouth sores. However, the use of antibiotics and steroids may promote the development of the fungus candida that can cause thrush or oral candidiasis.If treatment is started early, symptomatic relief may occur during the first day of treatment and new lesions may be healed. Recurring oral ulcers generally require renewed efforts at treatment. Other treatment is symptomatic and supportive.
|
Therapies of Sutton Disease II. The symptomatic treatment of Sutton disease II involves the application of topical anesthetic (i.e., lidocaine viscous) directly on the affected areas or a thorough mouth rinsing with a special anesthetic solution that helps to reduce irritation and pain. The application of topical steroids may also give symptomatic relief. A dental protective paste (i.e., triamcinolone acetonide or Orabase) may prevent teeth, dental appliances and oral fluids from irritating the ulcers.In severe cases of Sutton disease II, oral and topical steroids may be administered. A mouthrinse that contains the antibiotic tetracycline may also be prescribed to heal painful mouth sores. However, the use of antibiotics and steroids may promote the development of the fungus candida that can cause thrush or oral candidiasis.If treatment is started early, symptomatic relief may occur during the first day of treatment and new lesions may be healed. Recurring oral ulcers generally require renewed efforts at treatment. Other treatment is symptomatic and supportive.
| 1,177 |
Sutton Disease II
|
nord_1178_0
|
Overview of Sweet Syndrome
|
Sweet syndrome is a rare disorder characterized by fever and the sudden onset of a rash, which consists of multiple tender, red or bluish-red bumps or lesions. These lesions usually occur on the arms, legs, trunk, face or neck. In some cases, additional systems of the body can become involved including the musculoskeletal system such as inflammation of the joints (arthritis), the eyes such as inflammation of the conjunctiva or the membrane that lines the eyes (conjunctivitis), and the internal organs. In the majority of affected individuals, the disorder occurs by itself for no known reason (idiopathic Sweet syndrome); this is also known as classical Sweet syndrome. Less often, the disorder can be associated with an underlying cancer (malignancy), usually a blood (hematologic) cancer such as certain types of leukemia; this is known as malignancy-associated Sweet syndrome. The disorder can also result as a reaction to taking certain drugs, especially a drug known as granulocyte-colony stimulating factor; this is known as drug-induced Sweet syndrome. Sweet syndrome is treated with corticosteroids.IntroductionSweet syndrome was first described in the medical literature in 1964 by Dr. Robert Douglas Sweet. The disorder is classified as a neutrophilic dermatosis, which is a general term for a group of skin disorders characterized by the accumulation of neutrophils in the skin. Neutrophils are a specific type of white blood cell that is instrumental in fighting off infection by surrounding and destroying bacteria that enter the body. In Sweet syndrome neutrophils accumulate in the dermis, the thick layer of tissue just below the outer layer of the skin (epidermis).
|
Overview of Sweet Syndrome. Sweet syndrome is a rare disorder characterized by fever and the sudden onset of a rash, which consists of multiple tender, red or bluish-red bumps or lesions. These lesions usually occur on the arms, legs, trunk, face or neck. In some cases, additional systems of the body can become involved including the musculoskeletal system such as inflammation of the joints (arthritis), the eyes such as inflammation of the conjunctiva or the membrane that lines the eyes (conjunctivitis), and the internal organs. In the majority of affected individuals, the disorder occurs by itself for no known reason (idiopathic Sweet syndrome); this is also known as classical Sweet syndrome. Less often, the disorder can be associated with an underlying cancer (malignancy), usually a blood (hematologic) cancer such as certain types of leukemia; this is known as malignancy-associated Sweet syndrome. The disorder can also result as a reaction to taking certain drugs, especially a drug known as granulocyte-colony stimulating factor; this is known as drug-induced Sweet syndrome. Sweet syndrome is treated with corticosteroids.IntroductionSweet syndrome was first described in the medical literature in 1964 by Dr. Robert Douglas Sweet. The disorder is classified as a neutrophilic dermatosis, which is a general term for a group of skin disorders characterized by the accumulation of neutrophils in the skin. Neutrophils are a specific type of white blood cell that is instrumental in fighting off infection by surrounding and destroying bacteria that enter the body. In Sweet syndrome neutrophils accumulate in the dermis, the thick layer of tissue just below the outer layer of the skin (epidermis).
| 1,178 |
Sweet Syndrome
|
nord_1178_1
|
Symptoms of Sweet Syndrome
|
The major symptom of Sweet syndrome is the sudden onset of tender or painful bumps (nodules or papules) on the arms, legs, face or neck. They may also occur on the thighs and trunk. Papules are solid, raises lesions; nodules are slightly larger and may extend deeper into the skin. These initial lesions are usually several millimeters to centimeters in diameter, but sometimes up to an inch in diameter, flat or slightly elevated, irregularly-shaped, and inflamed. They tend to grow slowly, eventually joining together (coalescing) to form larger, irregular plaques. Small pus-filled blisters (pustules) may develop.In some individuals, neutrophils may accumulated in the fatty layer of tissue just below the skin (subcutaneous fat) rather than in the dermis. Affected individuals often develop reddish (erythematous) discoloration of the skin and small bumps (nodules) on the skin. The arms and legs are most often affected.Individuals with Sweet syndrome also experience fever, fatigue, headaches, a general feeling of ill health (malaise), muscle pain (myalgia), and inflammation and pain of the joints (arthritis and arthralgia). Fever can precede the development of skin symptoms by days or weeks.Sweet syndrome can potentially affect most organ systems of the body. The most common organ system involved outside of the skin is the eyes. Affected individuals can develop inflammation of the conjunctiva, the delicate membrane that lines the eyes (conjunctivitis) or inflammation of the thin layer of tissue (episclera) covering the whites of the eyes (episcleritis). Less often, additional symptoms can occur including the formation of bumps on the limbus, which is the border of the cornea and the whites of the eyes (limbal nodules), glaucoma, inflammation of the iris, which is the colored portion of the eye (iritis), and inflammation and ulceration of the cornea (peripheral ulcerative keratitis).In most individuals, Sweet syndrome occurs without any underlying disorder. In these individuals with classic Sweet syndrome, onset of the disorder usually follows an infection of the upper respiratory tract or gastrointestinal system.Less often, Sweet syndrome is associated with a malignancy, most often a malignancy that affects the blood (hematologic malignancies), such as certain types of leukemia and, rarely, cancers of the genitourinary and gastrointestinal tracts. In some cases, individuals with malignancy-associated Sweet syndrome may have lesions affecting the mucous membranes of the mouth (oral mucosa).Drug-induced Sweet syndrome has skin (cutaneous) symptoms are similar to those seen in the classical form.
|
Symptoms of Sweet Syndrome. The major symptom of Sweet syndrome is the sudden onset of tender or painful bumps (nodules or papules) on the arms, legs, face or neck. They may also occur on the thighs and trunk. Papules are solid, raises lesions; nodules are slightly larger and may extend deeper into the skin. These initial lesions are usually several millimeters to centimeters in diameter, but sometimes up to an inch in diameter, flat or slightly elevated, irregularly-shaped, and inflamed. They tend to grow slowly, eventually joining together (coalescing) to form larger, irregular plaques. Small pus-filled blisters (pustules) may develop.In some individuals, neutrophils may accumulated in the fatty layer of tissue just below the skin (subcutaneous fat) rather than in the dermis. Affected individuals often develop reddish (erythematous) discoloration of the skin and small bumps (nodules) on the skin. The arms and legs are most often affected.Individuals with Sweet syndrome also experience fever, fatigue, headaches, a general feeling of ill health (malaise), muscle pain (myalgia), and inflammation and pain of the joints (arthritis and arthralgia). Fever can precede the development of skin symptoms by days or weeks.Sweet syndrome can potentially affect most organ systems of the body. The most common organ system involved outside of the skin is the eyes. Affected individuals can develop inflammation of the conjunctiva, the delicate membrane that lines the eyes (conjunctivitis) or inflammation of the thin layer of tissue (episclera) covering the whites of the eyes (episcleritis). Less often, additional symptoms can occur including the formation of bumps on the limbus, which is the border of the cornea and the whites of the eyes (limbal nodules), glaucoma, inflammation of the iris, which is the colored portion of the eye (iritis), and inflammation and ulceration of the cornea (peripheral ulcerative keratitis).In most individuals, Sweet syndrome occurs without any underlying disorder. In these individuals with classic Sweet syndrome, onset of the disorder usually follows an infection of the upper respiratory tract or gastrointestinal system.Less often, Sweet syndrome is associated with a malignancy, most often a malignancy that affects the blood (hematologic malignancies), such as certain types of leukemia and, rarely, cancers of the genitourinary and gastrointestinal tracts. In some cases, individuals with malignancy-associated Sweet syndrome may have lesions affecting the mucous membranes of the mouth (oral mucosa).Drug-induced Sweet syndrome has skin (cutaneous) symptoms are similar to those seen in the classical form.
| 1,178 |
Sweet Syndrome
|
nord_1178_2
|
Causes of Sweet Syndrome
|
The exact cause of Sweet syndrome is not fully understood. Most likely, the disorder results from multiple, complex factors including immunological, and environmental factors. Some researchers speculate that Sweet syndrome occurs as an allergic reaction (reactive process) to an unknown agent. In such instances, there is an oversensitive, or hypersensitivity, reaction by the immune system to a specific agent such as a bacterial or viral infection, cancer or certain type of drug. Cytokine dysregulation may also play a role in the development of the disorder. Cytokines are specialized proteins secreted from certain immune system cells that either stimulate or inhibit the function of other immune system cells. If these cytokines malfunction, it can result in overstimulation of the immune system in response to a specific agent. Many people with classic Sweet syndrome experience an upper respiratory infection, gastrointestinal infection, or influenza-like illness that precedes their skin lesions by one to three weeks. In women, classic Sweet syndrome may occur during pregnancy. Pregnancy-associated Sweet syndrome typically presents in the first or second trimester. There does not appear to be any fetal risk, and the syndrome may recur with subsequent pregnancies.In some cases, classic Sweet syndrome may also be associated with autoimmune and inflammatory disorders such as inflammatory bowel disease: ulcerative colitis or Crohn’s disease. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Drug-induced Sweet syndrome develops after using certain medications, the most commonly associated drug is known as granulocyte-colony stimulating factor. This drug is used to stimulate the production of neutrophils. A wide variety of additional drugs have been associated with Sweet syndrome, although less often. Malignancy-associated Sweet syndrome is most commonly associated with blood cancers such as leukemia and lymphoma and solid tumors including breast cancer. More research is necessary to determine the exact underlying mechanisms that contribute to and ultimately cause the development of Sweet syndrome.
|
Causes of Sweet Syndrome. The exact cause of Sweet syndrome is not fully understood. Most likely, the disorder results from multiple, complex factors including immunological, and environmental factors. Some researchers speculate that Sweet syndrome occurs as an allergic reaction (reactive process) to an unknown agent. In such instances, there is an oversensitive, or hypersensitivity, reaction by the immune system to a specific agent such as a bacterial or viral infection, cancer or certain type of drug. Cytokine dysregulation may also play a role in the development of the disorder. Cytokines are specialized proteins secreted from certain immune system cells that either stimulate or inhibit the function of other immune system cells. If these cytokines malfunction, it can result in overstimulation of the immune system in response to a specific agent. Many people with classic Sweet syndrome experience an upper respiratory infection, gastrointestinal infection, or influenza-like illness that precedes their skin lesions by one to three weeks. In women, classic Sweet syndrome may occur during pregnancy. Pregnancy-associated Sweet syndrome typically presents in the first or second trimester. There does not appear to be any fetal risk, and the syndrome may recur with subsequent pregnancies.In some cases, classic Sweet syndrome may also be associated with autoimmune and inflammatory disorders such as inflammatory bowel disease: ulcerative colitis or Crohn’s disease. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Drug-induced Sweet syndrome develops after using certain medications, the most commonly associated drug is known as granulocyte-colony stimulating factor. This drug is used to stimulate the production of neutrophils. A wide variety of additional drugs have been associated with Sweet syndrome, although less often. Malignancy-associated Sweet syndrome is most commonly associated with blood cancers such as leukemia and lymphoma and solid tumors including breast cancer. More research is necessary to determine the exact underlying mechanisms that contribute to and ultimately cause the development of Sweet syndrome.
| 1,178 |
Sweet Syndrome
|
nord_1178_3
|
Affects of Sweet Syndrome
|
Classical Sweet syndrome in adults affects women more often than men by as much as 15:1 by some estimates. This female preponderance has not been seen in malignancy-associated or drug-induced Sweet syndrome. Classical Sweet syndrome usually affects women between the ages of 30-50, but can be seen in individuals of any age including children. There is no gender predominance seen in children. Several hundred individuals of Sweet syndrome have been reported in the medical literature. Only approximately 80 children have been reported in the medical literature.
|
Affects of Sweet Syndrome. Classical Sweet syndrome in adults affects women more often than men by as much as 15:1 by some estimates. This female preponderance has not been seen in malignancy-associated or drug-induced Sweet syndrome. Classical Sweet syndrome usually affects women between the ages of 30-50, but can be seen in individuals of any age including children. There is no gender predominance seen in children. Several hundred individuals of Sweet syndrome have been reported in the medical literature. Only approximately 80 children have been reported in the medical literature.
| 1,178 |
Sweet Syndrome
|
nord_1178_4
|
Related disorders of Sweet Syndrome
|
Symptoms of the following disorders can be similar to those of Sweet syndrome. Comparisons may be useful for a differential diagnosis:Pyoderma gangrenosum is a rare skin disorder of unknown origin. Major symptoms include small pustules that develop into large ulcers at various sites on the body. Skin abnormalities associated with pyoderma gangrenosum are slowly growing, purple-colored lesions with an undermined border and an irregular base of pus and decaying tissue. The ulcers most frequently develop on the legs but they may appear on the trunk, head and neck, scrotum and in the mucous membranes (mucosa). (For more information on this disorder, choose “pyoderma gangrenosum” as your search term in the Rare Disease Database.)Erythema multiforme is an inflammatory skin disorder characterized by symmetric red and blistery (bullous) lesions of the skin or mucous membranes of the hands, feet and eyelids. In most cases, onset of erythema multiforme is sudden with red spots (macules or papules), or ridges (wheals), and sometimes blisters, appearing mainly on the back of hands, feet and face. Bleeding lesions on the lips and the mucous membranes in the mouth may also occur. The skin lesions are usually distributed on both sides of the body and they often appear as rings, with concentric circles having a grayish discoloration in the center. Itching can also occur. Additional symptoms vary and may include malaise, pain in the joints (arthralgia), muscular stiffness and fever. Attacks usually last between two and four weeks and may recur during the fall and spring for several years. (For more information on this disorder, choose “erythema multiforme” as your search term in the Rare Disease Database.)The symptoms of Sweet syndrome may resemble those seen in other skin (cutaneous) and systemic disorders including dermatomyositis, CANDLE syndrome, allergic contact dermatitis, cellulitis, erythema nodosum, acral erythema, bacterial sepsis, neutrophilic rheumatoid arthritis, panniculitis, leukemia cutis, leukocytoclastic vasculitis, Schintzler’s syndrome, lupus, leukemia cutis, and many others. A variety of drug-induced skin reactions can also resemble Sweet syndrome.
|
Related disorders of Sweet Syndrome. Symptoms of the following disorders can be similar to those of Sweet syndrome. Comparisons may be useful for a differential diagnosis:Pyoderma gangrenosum is a rare skin disorder of unknown origin. Major symptoms include small pustules that develop into large ulcers at various sites on the body. Skin abnormalities associated with pyoderma gangrenosum are slowly growing, purple-colored lesions with an undermined border and an irregular base of pus and decaying tissue. The ulcers most frequently develop on the legs but they may appear on the trunk, head and neck, scrotum and in the mucous membranes (mucosa). (For more information on this disorder, choose “pyoderma gangrenosum” as your search term in the Rare Disease Database.)Erythema multiforme is an inflammatory skin disorder characterized by symmetric red and blistery (bullous) lesions of the skin or mucous membranes of the hands, feet and eyelids. In most cases, onset of erythema multiforme is sudden with red spots (macules or papules), or ridges (wheals), and sometimes blisters, appearing mainly on the back of hands, feet and face. Bleeding lesions on the lips and the mucous membranes in the mouth may also occur. The skin lesions are usually distributed on both sides of the body and they often appear as rings, with concentric circles having a grayish discoloration in the center. Itching can also occur. Additional symptoms vary and may include malaise, pain in the joints (arthralgia), muscular stiffness and fever. Attacks usually last between two and four weeks and may recur during the fall and spring for several years. (For more information on this disorder, choose “erythema multiforme” as your search term in the Rare Disease Database.)The symptoms of Sweet syndrome may resemble those seen in other skin (cutaneous) and systemic disorders including dermatomyositis, CANDLE syndrome, allergic contact dermatitis, cellulitis, erythema nodosum, acral erythema, bacterial sepsis, neutrophilic rheumatoid arthritis, panniculitis, leukemia cutis, leukocytoclastic vasculitis, Schintzler’s syndrome, lupus, leukemia cutis, and many others. A variety of drug-induced skin reactions can also resemble Sweet syndrome.
| 1,178 |
Sweet Syndrome
|
nord_1178_5
|
Diagnosis of Sweet Syndrome
|
A diagnosis of Sweet syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of classic symptoms, and a variety of specialized tests. In many cases, surgical removal (biopsy) and microscopic examination of small samples of skin tissue may reveal the infiltrate of neutrophils in the dermis. A complete blood cell count may also show neutrophils in the blood (neutrophilia).
|
Diagnosis of Sweet Syndrome. A diagnosis of Sweet syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of classic symptoms, and a variety of specialized tests. In many cases, surgical removal (biopsy) and microscopic examination of small samples of skin tissue may reveal the infiltrate of neutrophils in the dermis. A complete blood cell count may also show neutrophils in the blood (neutrophilia).
| 1,178 |
Sweet Syndrome
|
nord_1178_6
|
Therapies of Sweet Syndrome
|
TreatmentThe treatment of Sweet syndrome is directed toward the specific symptoms that are apparent in each individual. In some cases, Sweet syndrome may resolve itself with no treatment, although this can take weeks to months. The mainstay of treatment is with systemic corticosteroids. In most cases, treatment with low doses of corticosteroids such as methylprednisolone or prednisone has proven effective in eliminating symptoms, sometimes rapidly resolving symptoms. However, Sweet syndrome often recurs periodically despite therapy. For isolated lesions, local therapy may consist of topical corticosteroids (creams of gels) or directly injecting corticosteroids into the lesion (intralesional corticosteroid).Other drugs have been used to treat individuals with Sweet syndrome including colchicine, dapsone, and potassium iodide. These drugs are generally used for individuals who cannot tolerate corticosteroids, in whom corticosteroids were ineffective, or when trying to lower the dose of (taper) the corticosteroid. A variety of additional drugs have been used to treat individuals with Sweet syndrome including cyclosporine, indomethacin and clofazimine.Individuals with Sweet syndrome should receive a thorough clinical examination to detect any possible underlying malignancy or disorder that may be associated with Sweet syndrome, including a complete hematologic evaluation. Usually, treatment of the underlying cancer results in the resolution of symptoms in malignancy-associated Sweet syndrome. However, treatment with corticosteroids as with the classic form is often recommended.Drug-induced Sweet syndrome usually goes away after the affected individual stops taking the offending medication. Treatment with corticosteroids may also be used to treat this form of Sweet syndrome.The skin lesions associated with Sweet syndrome usually heal without scars, unless open sores were present (ulceration). The affected area may remain discolored for months after the lesion has resolved.Although corticosteroids are the mainstay of treatment and often effective in treating Sweet syndrome, there are no standardized treatment protocols for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Sweet syndrome.
|
Therapies of Sweet Syndrome. TreatmentThe treatment of Sweet syndrome is directed toward the specific symptoms that are apparent in each individual. In some cases, Sweet syndrome may resolve itself with no treatment, although this can take weeks to months. The mainstay of treatment is with systemic corticosteroids. In most cases, treatment with low doses of corticosteroids such as methylprednisolone or prednisone has proven effective in eliminating symptoms, sometimes rapidly resolving symptoms. However, Sweet syndrome often recurs periodically despite therapy. For isolated lesions, local therapy may consist of topical corticosteroids (creams of gels) or directly injecting corticosteroids into the lesion (intralesional corticosteroid).Other drugs have been used to treat individuals with Sweet syndrome including colchicine, dapsone, and potassium iodide. These drugs are generally used for individuals who cannot tolerate corticosteroids, in whom corticosteroids were ineffective, or when trying to lower the dose of (taper) the corticosteroid. A variety of additional drugs have been used to treat individuals with Sweet syndrome including cyclosporine, indomethacin and clofazimine.Individuals with Sweet syndrome should receive a thorough clinical examination to detect any possible underlying malignancy or disorder that may be associated with Sweet syndrome, including a complete hematologic evaluation. Usually, treatment of the underlying cancer results in the resolution of symptoms in malignancy-associated Sweet syndrome. However, treatment with corticosteroids as with the classic form is often recommended.Drug-induced Sweet syndrome usually goes away after the affected individual stops taking the offending medication. Treatment with corticosteroids may also be used to treat this form of Sweet syndrome.The skin lesions associated with Sweet syndrome usually heal without scars, unless open sores were present (ulceration). The affected area may remain discolored for months after the lesion has resolved.Although corticosteroids are the mainstay of treatment and often effective in treating Sweet syndrome, there are no standardized treatment protocols for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Sweet syndrome.
| 1,178 |
Sweet Syndrome
|
nord_1179_0
|
Overview of Swyer syndrome
|
SummarySwyer syndrome is a rare disorder characterized by the failure of the sex glands (i.e., testicles or ovaries) to develop. Swyer syndrome is classified as a disorder of sex development (DSD), which encompasses any disorder in which chromosomal, gonadal or anatomic sex development is abnormal. Girls with Swyer syndrome have an XY chromosomal makeup (as boys normally do) instead of an XX chromosomal makeup (as girls normally do). Despite having the XY chromosomal makeup, girls with Swyer syndrome look female and have functional female genitalia and structures including a vagina, uterus and fallopian tubes.Girls with Swyer syndrome lack sex glands (ovaries). Instead of sex glands, women with Swyer syndrome have “gonadal streaks”, in which the ovaries do not develop properly (aplasia) and are replaced by functionless scar (fibrous) tissue. Because they lack ovaries, girls with Swyer syndrome do not produce sex hormones and will not undergo puberty (unless treated with hormone replacement therapy). Mutations in several different genes are known to cause Swyer syndrome. This condition can occur as the result of a new gene mutation or can be inherited in an autosomal dominant, autosomal recessive, X-linked or Y-linked manner.IntoductionSwyer syndrome was first described in the medical literature by Dr. Swyer in 1955.
|
Overview of Swyer syndrome. SummarySwyer syndrome is a rare disorder characterized by the failure of the sex glands (i.e., testicles or ovaries) to develop. Swyer syndrome is classified as a disorder of sex development (DSD), which encompasses any disorder in which chromosomal, gonadal or anatomic sex development is abnormal. Girls with Swyer syndrome have an XY chromosomal makeup (as boys normally do) instead of an XX chromosomal makeup (as girls normally do). Despite having the XY chromosomal makeup, girls with Swyer syndrome look female and have functional female genitalia and structures including a vagina, uterus and fallopian tubes.Girls with Swyer syndrome lack sex glands (ovaries). Instead of sex glands, women with Swyer syndrome have “gonadal streaks”, in which the ovaries do not develop properly (aplasia) and are replaced by functionless scar (fibrous) tissue. Because they lack ovaries, girls with Swyer syndrome do not produce sex hormones and will not undergo puberty (unless treated with hormone replacement therapy). Mutations in several different genes are known to cause Swyer syndrome. This condition can occur as the result of a new gene mutation or can be inherited in an autosomal dominant, autosomal recessive, X-linked or Y-linked manner.IntoductionSwyer syndrome was first described in the medical literature by Dr. Swyer in 1955.
| 1,179 |
Swyer syndrome
|
nord_1179_1
|
Symptoms of Swyer syndrome
|
Most individuals with Swyer syndrome do not experience any outward symptoms until their early teens when they fail to begin having a period (primary amenorrhea). At this point, it is usually discovered that these girls lack ovaries and, therefore, do not have sex hormones (estrogen or progesterone) that are required to undergo puberty. When hormone replacement therapy is started, these girls will develop enlarged breasts, underarm and pubic hair, regular menstrual cycles and other aspects of normal development during puberty.Women with Swyer syndrome may be tall and often have a small uterus and a slightly enlarged clitoris in comparison to most women. Because women with Swyer syndrome lack ovaries, they are infertile. However, they can become pregnant through the implantation of donated eggs.A chief medical concern of women with Swyer syndrome is an increased risk of developing cancer of the underdeveloped gonadal tissue. Approximately 30 percent of women with Swyer syndrome develop a tumor that arises from the cells that forms the testes or ovaries (gonadal tumor). The most common gonadal tumor in women with Swyer syndrome is a gonadoblastoma, a benign (non-cancerous) tumor that occurs exclusively in people with defective development of the gonads. A gonadoblastoma usually does not become malignant or spread. Gonadoblastomas, however, may be precursors to the development of a malignant (cancerous) tumor such as a dysgerminoma, which has also been reported to occur with greater frequency in women with Swyer syndrome than in the general population.Gonadal tumors can develop at any age including during childhood before a diagnosis of Swyer syndrome is even suspected.
|
Symptoms of Swyer syndrome. Most individuals with Swyer syndrome do not experience any outward symptoms until their early teens when they fail to begin having a period (primary amenorrhea). At this point, it is usually discovered that these girls lack ovaries and, therefore, do not have sex hormones (estrogen or progesterone) that are required to undergo puberty. When hormone replacement therapy is started, these girls will develop enlarged breasts, underarm and pubic hair, regular menstrual cycles and other aspects of normal development during puberty.Women with Swyer syndrome may be tall and often have a small uterus and a slightly enlarged clitoris in comparison to most women. Because women with Swyer syndrome lack ovaries, they are infertile. However, they can become pregnant through the implantation of donated eggs.A chief medical concern of women with Swyer syndrome is an increased risk of developing cancer of the underdeveloped gonadal tissue. Approximately 30 percent of women with Swyer syndrome develop a tumor that arises from the cells that forms the testes or ovaries (gonadal tumor). The most common gonadal tumor in women with Swyer syndrome is a gonadoblastoma, a benign (non-cancerous) tumor that occurs exclusively in people with defective development of the gonads. A gonadoblastoma usually does not become malignant or spread. Gonadoblastomas, however, may be precursors to the development of a malignant (cancerous) tumor such as a dysgerminoma, which has also been reported to occur with greater frequency in women with Swyer syndrome than in the general population.Gonadal tumors can develop at any age including during childhood before a diagnosis of Swyer syndrome is even suspected.
| 1,179 |
Swyer syndrome
|
nord_1179_2
|
Causes of Swyer syndrome
|
In most cases of Swyer syndrome, the exact cause of the disorder is unknown. Researchers believe that disruptions or changes (mutations) of a gene or genes that are involved in normal sex differentiation of a fetus with an XY chromosomal makeup cause Swyer syndrome.Genes are sequences of DNA that are found on a specific location of a chromosome and are the basic unit of inheritance. Genes determine a particular characteristic or trait in a person. 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 called autosomes. The sex chromosomes are designated X and Y. Males usually have one X and one Y chromosome and females usually have two X chromosomes.In approximately 15-20 percent of patients, Swyer syndrome occurs due to mutations of the sex-determining region Y (SRY) gene on the Y chromosome or deletion of the segment of the Y chromosome containing the SRY gene. The SRY gene is believed to be critical in initiating male sex determination by triggering undifferentiated gonadal tissue to transform into testes. Absence or mutation of this gene results in the failure of the testes to form.Since only 15-20 percent of women with Swyer syndrome have a mutation of the SRY gene, researchers believe that defects involving other genes can also cause the disorder. These other genes are all suspected to play a role in the promoting the development of the testes and, ultimately, the differentiation of an XY fetus into a male. Mutations in the Map3K1 are also a common cause of Swyer syndrome. Some women with Swyer syndrome have mutations in the NROB1 gene on the X chromosome. Investigators have linked other cases of Swyer syndrome to mutations of the desert hedgehog (DHH) gene located on chromosome 12. Mutations in the DEAH37 gene have been identified as a common cause. A few rare cases have been associated with mutations in the steroidogenic factor 1 (SF1 or NR5A1) gene, the protein Wnt-4 (WNT4) gene, and the CBX2, GATA4 and WWOX genes. Researchers believe that additional, as yet unidentified, genes may also be associated with the development of Swyer syndrome.Some cases of Swyer syndrome are not believed to be inherited, but rather the result of a new genetic mutation (de novo mutation) or abnormality that occurs for unknown reasons (spontaneously). However, some women with Swyer syndrome due to mutation of the SRY gene have had fathers (and some even brothers) who also have the SRY mutation on the Y chromosome. It is not known why, in these cases, the fathers and/or brothers did not develop Swyer syndrome. Researchers speculate that other genes and/or factors in combination with a mutation of the SRY gene may be necessary for the development of Swyer syndrome in these patients.Cases of Swyer syndrome due to mutation of the NROB1 gene may be inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females usually have two X chromosomes and 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 usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. However, because women with Swyer syndrome have an XY chromosomal makeup and lack a second X chromosome, they will express symptoms associated with a defect on their one X chromosome.According to the medical literature, some cases of Swyer syndrome appear to follow autosomal dominant or recessive inheritance. Mutations of the WNT4, MAP3K1 or the SF1 (NR5A1) genes may be inherited in as autosomal dominant pattern. Mutation of the DHH gene may be inherited in an autosomal recessive manner.Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from 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. 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. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. Affected individuals are encouraged to seek genetic counseling for answers to any questions regarding the complex genetic factors involved in Swyer syndrome. For information on genetic counseling, see the Resources section of this report.
|
Causes of Swyer syndrome. In most cases of Swyer syndrome, the exact cause of the disorder is unknown. Researchers believe that disruptions or changes (mutations) of a gene or genes that are involved in normal sex differentiation of a fetus with an XY chromosomal makeup cause Swyer syndrome.Genes are sequences of DNA that are found on a specific location of a chromosome and are the basic unit of inheritance. Genes determine a particular characteristic or trait in a person. 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 called autosomes. The sex chromosomes are designated X and Y. Males usually have one X and one Y chromosome and females usually have two X chromosomes.In approximately 15-20 percent of patients, Swyer syndrome occurs due to mutations of the sex-determining region Y (SRY) gene on the Y chromosome or deletion of the segment of the Y chromosome containing the SRY gene. The SRY gene is believed to be critical in initiating male sex determination by triggering undifferentiated gonadal tissue to transform into testes. Absence or mutation of this gene results in the failure of the testes to form.Since only 15-20 percent of women with Swyer syndrome have a mutation of the SRY gene, researchers believe that defects involving other genes can also cause the disorder. These other genes are all suspected to play a role in the promoting the development of the testes and, ultimately, the differentiation of an XY fetus into a male. Mutations in the Map3K1 are also a common cause of Swyer syndrome. Some women with Swyer syndrome have mutations in the NROB1 gene on the X chromosome. Investigators have linked other cases of Swyer syndrome to mutations of the desert hedgehog (DHH) gene located on chromosome 12. Mutations in the DEAH37 gene have been identified as a common cause. A few rare cases have been associated with mutations in the steroidogenic factor 1 (SF1 or NR5A1) gene, the protein Wnt-4 (WNT4) gene, and the CBX2, GATA4 and WWOX genes. Researchers believe that additional, as yet unidentified, genes may also be associated with the development of Swyer syndrome.Some cases of Swyer syndrome are not believed to be inherited, but rather the result of a new genetic mutation (de novo mutation) or abnormality that occurs for unknown reasons (spontaneously). However, some women with Swyer syndrome due to mutation of the SRY gene have had fathers (and some even brothers) who also have the SRY mutation on the Y chromosome. It is not known why, in these cases, the fathers and/or brothers did not develop Swyer syndrome. Researchers speculate that other genes and/or factors in combination with a mutation of the SRY gene may be necessary for the development of Swyer syndrome in these patients.Cases of Swyer syndrome due to mutation of the NROB1 gene may be inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females usually have two X chromosomes and 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 usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. However, because women with Swyer syndrome have an XY chromosomal makeup and lack a second X chromosome, they will express symptoms associated with a defect on their one X chromosome.According to the medical literature, some cases of Swyer syndrome appear to follow autosomal dominant or recessive inheritance. Mutations of the WNT4, MAP3K1 or the SF1 (NR5A1) genes may be inherited in as autosomal dominant pattern. Mutation of the DHH gene may be inherited in an autosomal recessive manner.Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from 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. 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. All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. Affected individuals are encouraged to seek genetic counseling for answers to any questions regarding the complex genetic factors involved in Swyer syndrome. For information on genetic counseling, see the Resources section of this report.
| 1,179 |
Swyer syndrome
|
nord_1179_3
|
Affects of Swyer syndrome
|
Swyer syndrome affects girls who have an XY chromosomal makeup, no ovaries, but functional female organs including the uterus, fallopian tubes and vagina. The exact incidence is unknown. One estimate placed the incidence at 1 in 80,000 births. Another estimate placed the incidence of Swyer syndrome (complete gonadal dysgenesis) and partial gonadal dysgenesis combined at 1 in 20,000 births. Genital anomalies in general occur in approximately 1 in 4,500 births.
|
Affects of Swyer syndrome. Swyer syndrome affects girls who have an XY chromosomal makeup, no ovaries, but functional female organs including the uterus, fallopian tubes and vagina. The exact incidence is unknown. One estimate placed the incidence at 1 in 80,000 births. Another estimate placed the incidence of Swyer syndrome (complete gonadal dysgenesis) and partial gonadal dysgenesis combined at 1 in 20,000 births. Genital anomalies in general occur in approximately 1 in 4,500 births.
| 1,179 |
Swyer syndrome
|
nord_1179_4
|
Related disorders of Swyer syndrome
|
Symptoms of the following disorders can be similar to those of Swyer syndrome. Comparisons may be useful for a differential diagnosis.46, XY disorder of sex development is a rare congenital disorder in which individuals have a 46, XY chromosomal makeup, external genitalia that are not fully developed and/or may have characteristics of both sexes (ambiguous genitalia), and abnormal formation of the testes (partial gonadal dysgenesis) with reduced or no sperm production. Some individuals may have the urinary opening on the underside of the penis (hypospadias) with downward curvature of the penis (chordee). Some individuals may have complete absence of the Mullerian structures (vagina, uterus and fallopian tubes) to fully a developed uterus and fallopian tubes. Individuals with 46, XY DSD are at a greater risk than the general population of developing a gonadal tumor such as a gonadoblastoma or dysgerminoma.Disorders of sex development (DSDs) refer to a group of congenital disorders in which the development of abnormal chromosomal, gonadal, or anatomic sex is atypical. Symptoms of these disorders can vary greatly, but can include ambiguous genitalia, female genitalia with an enlarged clitoris, male genitalia with undescended testes, micropenis, improper placement of the urinary opening on the underside of the penis (hypospadias), and a defect in the part of the embryo that develops into the lower abdominal wall (cloaca), potentially exposing lower abdominal and nearby structures such as the urethra, bladder and bowel (cloacal extrophy). This group of disorders includes complete or partial androgen insensitivity, 5-alpha reductase deficiency, congenital adrenal hyperplasia, ovotesticular DSD (formerly true hermaphroditism), and other disorders. The causes of these disorders vary. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
|
Related disorders of Swyer syndrome. Symptoms of the following disorders can be similar to those of Swyer syndrome. Comparisons may be useful for a differential diagnosis.46, XY disorder of sex development is a rare congenital disorder in which individuals have a 46, XY chromosomal makeup, external genitalia that are not fully developed and/or may have characteristics of both sexes (ambiguous genitalia), and abnormal formation of the testes (partial gonadal dysgenesis) with reduced or no sperm production. Some individuals may have the urinary opening on the underside of the penis (hypospadias) with downward curvature of the penis (chordee). Some individuals may have complete absence of the Mullerian structures (vagina, uterus and fallopian tubes) to fully a developed uterus and fallopian tubes. Individuals with 46, XY DSD are at a greater risk than the general population of developing a gonadal tumor such as a gonadoblastoma or dysgerminoma.Disorders of sex development (DSDs) refer to a group of congenital disorders in which the development of abnormal chromosomal, gonadal, or anatomic sex is atypical. Symptoms of these disorders can vary greatly, but can include ambiguous genitalia, female genitalia with an enlarged clitoris, male genitalia with undescended testes, micropenis, improper placement of the urinary opening on the underside of the penis (hypospadias), and a defect in the part of the embryo that develops into the lower abdominal wall (cloaca), potentially exposing lower abdominal and nearby structures such as the urethra, bladder and bowel (cloacal extrophy). This group of disorders includes complete or partial androgen insensitivity, 5-alpha reductase deficiency, congenital adrenal hyperplasia, ovotesticular DSD (formerly true hermaphroditism), and other disorders. The causes of these disorders vary. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
| 1,179 |
Swyer syndrome
|
nord_1179_5
|
Diagnosis of Swyer syndrome
|
A diagnosis of Swyer syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings (e.g., no periods, streak gonads) and a variety of tests including chromosomal analysis. For example, a specific technique called fluorescent in situ hybridization (FISH) can be used to determine a person’s karyotype. A karyotype is a visual representation of a person’s chromosomal makeup, (i.e., the 46 chromosomes in a cell). These 46 chromosomes are broken down into 22 matched pairs (each pair has one chromosome received from the father and one receive from the mother). The sex chromosomes are seen as a separate pair, either XX or XY. A diagnosis of Swyer syndrome is usually made when young adults are tested for delayed puberty.Molecular genetic testing can determine whether one of the specific gene mutations that are associated with Swyer syndrome is present in an affected individual.Evaluation of immediate family members of an affected person can be helpful in determining if the condition is sporadic or inherited in that family.
|
Diagnosis of Swyer syndrome. A diagnosis of Swyer syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings (e.g., no periods, streak gonads) and a variety of tests including chromosomal analysis. For example, a specific technique called fluorescent in situ hybridization (FISH) can be used to determine a person’s karyotype. A karyotype is a visual representation of a person’s chromosomal makeup, (i.e., the 46 chromosomes in a cell). These 46 chromosomes are broken down into 22 matched pairs (each pair has one chromosome received from the father and one receive from the mother). The sex chromosomes are seen as a separate pair, either XX or XY. A diagnosis of Swyer syndrome is usually made when young adults are tested for delayed puberty.Molecular genetic testing can determine whether one of the specific gene mutations that are associated with Swyer syndrome is present in an affected individual.Evaluation of immediate family members of an affected person can be helpful in determining if the condition is sporadic or inherited in that family.
| 1,179 |
Swyer syndrome
|
nord_1179_6
|
Therapies of Swyer syndrome
|
TreatmentThe treatment of Swyer syndrome may require the coordinated efforts of a team of specialists. Pediatricians, pediatric endocrinologists, geneticists, urologists or gynecologists, psychologists or psychiatrists, social workers and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Swyer syndrome is treated with hormonal replacement therapy including replacing estrogen and progesterone that is usually begun from puberty onward. In addition to helping with normal development of secondary sexual characteristics, hormone replacement therapy can also help prevent bone loss and thinning (osteoporosis) later during life.Streak gonads are usually removed surgically because they place affected individuals at an increased risk of developing a gonadal tumor.Individuals with SF1 mutations may have adrenal insufficiency. This should be investigated and treated, if present.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.Although women with Swyer syndrome are infertile, they may become pregnant and carry to term through the use of donated eggs.
|
Therapies of Swyer syndrome. TreatmentThe treatment of Swyer syndrome may require the coordinated efforts of a team of specialists. Pediatricians, pediatric endocrinologists, geneticists, urologists or gynecologists, psychologists or psychiatrists, social workers and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Swyer syndrome is treated with hormonal replacement therapy including replacing estrogen and progesterone that is usually begun from puberty onward. In addition to helping with normal development of secondary sexual characteristics, hormone replacement therapy can also help prevent bone loss and thinning (osteoporosis) later during life.Streak gonads are usually removed surgically because they place affected individuals at an increased risk of developing a gonadal tumor.Individuals with SF1 mutations may have adrenal insufficiency. This should be investigated and treated, if present.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.Although women with Swyer syndrome are infertile, they may become pregnant and carry to term through the use of donated eggs.
| 1,179 |
Swyer syndrome
|
nord_1180_0
|
Overview of Sydenham Chorea
|
Summary Sydenham chorea is a rare neurological disorder characterized by sudden onset chorea, usually in childhood. Chorea is defined as random-appearing, continuous (while awake), involuntary movements which can affect the entire body. This often includes the face and tongue. Symptoms in arms and legs are often worse on one side of the body. Additional symptoms of Sydenham chorea may include slurring of speech and difficulty maintaining steady hand grip. Anxiety, sadness, inattention, and obsessive compulsive thoughts and behaviors may also occur. Sydenham chorea most often affects children over the age of 5 years and adolescents. Sydenham chorea usually develops within weeks to months following group A beta-hemolytic streptococcal infection and may occur as an isolated finding or as a major complication of acute rheumatic fever. It is considered an autoimmune disorder, meaning it occurs when the body's immune system (which normally responds to foreign substances) mistakenly targets part of the body, disrupting normal function.
|
Overview of Sydenham Chorea. Summary Sydenham chorea is a rare neurological disorder characterized by sudden onset chorea, usually in childhood. Chorea is defined as random-appearing, continuous (while awake), involuntary movements which can affect the entire body. This often includes the face and tongue. Symptoms in arms and legs are often worse on one side of the body. Additional symptoms of Sydenham chorea may include slurring of speech and difficulty maintaining steady hand grip. Anxiety, sadness, inattention, and obsessive compulsive thoughts and behaviors may also occur. Sydenham chorea most often affects children over the age of 5 years and adolescents. Sydenham chorea usually develops within weeks to months following group A beta-hemolytic streptococcal infection and may occur as an isolated finding or as a major complication of acute rheumatic fever. It is considered an autoimmune disorder, meaning it occurs when the body's immune system (which normally responds to foreign substances) mistakenly targets part of the body, disrupting normal function.
| 1,180 |
Sydenham Chorea
|
nord_1180_1
|
Symptoms of Sydenham Chorea
|
The severity of chorea and the presence of non-chorea symptoms of Sydenham chorea may vary greatly from one person to another. Most cases follow an identifiable streptococcal infection. Streptococcus is a group of bacteria that can cause several different infections, most commonly “strep throat” – often presenting with a sore throat (pharyngitis) or fever. Symptoms of Sydenham chorea may appear anywhere from 1 week to 6 months following streptococcal infection.The abnormal movements (chorea) that characterize Sydenham chorea usually emerge over hours, peaking within a few hours or days. Pediatricians and emergency physicians seldom see chorea and may not recognize it. Initially, doctors may misattribute the restless movements and involuntary facial expressions of Sydenham chorea to a child being extremely fidgety, hyperactive, clumsy and/or purposely uncooperative. Parents (and children) generally recognize however that these movements, even in mild cases, are a clear change from the child’s usual status.
The abnormal movements in Sydenham chorea range from subtle symptoms, affecting coordination and tasks such as writing, to severe symptoms, disrupting walking, talking, and performing basic tasks such as dressing, eating, or simply holding objects. Choreic movements may fluctuate through the day. In most cases, chorea disappears during sleep.In addition to choreic movements, individuals with Sydenham chorea may develop muscle weakness, slurred speech (dysarthria), diminished muscle tone (hypotonia), tics, obsessions, compulsions, inattention, anxiety, labile mood, and decreased verbal output. In some extremely rare cases (less than 2 percent), severe muscle weakness, irritability, or confusion may be profound and affected children may become bedridden, a condition sometimes referred to as paralytic chorea.Because Sydenham chorea is a complication of rheumatic fever, some individuals will have additional symptoms of joint arthritis or arthralgia, inflammation of the heart valves causing permanent damage to the valves, and ongoing fever. Sydenham chorea symptoms usually resolve within three weeks to six months. However, symptoms may last longer than one year. Occasionally, the symptoms of Sydenham chorea have recurred later during adult life, particularly in young women during the first trimester of pregnancy (so-called chorea gravidarum, which may represent a recurrence of Sydenham chorea in some cases).
|
Symptoms of Sydenham Chorea. The severity of chorea and the presence of non-chorea symptoms of Sydenham chorea may vary greatly from one person to another. Most cases follow an identifiable streptococcal infection. Streptococcus is a group of bacteria that can cause several different infections, most commonly “strep throat” – often presenting with a sore throat (pharyngitis) or fever. Symptoms of Sydenham chorea may appear anywhere from 1 week to 6 months following streptococcal infection.The abnormal movements (chorea) that characterize Sydenham chorea usually emerge over hours, peaking within a few hours or days. Pediatricians and emergency physicians seldom see chorea and may not recognize it. Initially, doctors may misattribute the restless movements and involuntary facial expressions of Sydenham chorea to a child being extremely fidgety, hyperactive, clumsy and/or purposely uncooperative. Parents (and children) generally recognize however that these movements, even in mild cases, are a clear change from the child’s usual status.
The abnormal movements in Sydenham chorea range from subtle symptoms, affecting coordination and tasks such as writing, to severe symptoms, disrupting walking, talking, and performing basic tasks such as dressing, eating, or simply holding objects. Choreic movements may fluctuate through the day. In most cases, chorea disappears during sleep.In addition to choreic movements, individuals with Sydenham chorea may develop muscle weakness, slurred speech (dysarthria), diminished muscle tone (hypotonia), tics, obsessions, compulsions, inattention, anxiety, labile mood, and decreased verbal output. In some extremely rare cases (less than 2 percent), severe muscle weakness, irritability, or confusion may be profound and affected children may become bedridden, a condition sometimes referred to as paralytic chorea.Because Sydenham chorea is a complication of rheumatic fever, some individuals will have additional symptoms of joint arthritis or arthralgia, inflammation of the heart valves causing permanent damage to the valves, and ongoing fever. Sydenham chorea symptoms usually resolve within three weeks to six months. However, symptoms may last longer than one year. Occasionally, the symptoms of Sydenham chorea have recurred later during adult life, particularly in young women during the first trimester of pregnancy (so-called chorea gravidarum, which may represent a recurrence of Sydenham chorea in some cases).
| 1,180 |
Sydenham Chorea
|
nord_1180_2
|
Causes of Sydenham Chorea
|
Sydenham chorea is believed to be an autoimmune disorder. Most cases develop following a streptococcal infection or more severe rheumatic fever. An autoimmune disorder occurs when the body’s immune system mistakenly reacts against healthy tissue. In Sydenham chorea, streptococcal infection induces the body’s immune system to produce antibodies to combat the infection. For unknown reasons, these antibodies persist and subsequently target certain cells in the joints, kidneys, heart, and, in the brain, specifically cells of the basal ganglia (a key part of the brain for controlling motor movements). Researchers believe this ultimately leads to the characteristic symptoms of Sydenham chorea.The exact underlying mechanisms that cause Sydenham chorea are poorly understood. Researchers believe that antigens (substances that are capable of stimulating an immune system response) on streptococcal bacterial cells are similar to antigens found on cells on the human body. When the immune system creates antibodies to combat the streptococcal infection, the antibodies also, in genetically predisposed individuals, mistakenly bind to healthy cells. When they bind to brain cells, they cause disruption in their “signaling” – their ability to control movement.
|
Causes of Sydenham Chorea. Sydenham chorea is believed to be an autoimmune disorder. Most cases develop following a streptococcal infection or more severe rheumatic fever. An autoimmune disorder occurs when the body’s immune system mistakenly reacts against healthy tissue. In Sydenham chorea, streptococcal infection induces the body’s immune system to produce antibodies to combat the infection. For unknown reasons, these antibodies persist and subsequently target certain cells in the joints, kidneys, heart, and, in the brain, specifically cells of the basal ganglia (a key part of the brain for controlling motor movements). Researchers believe this ultimately leads to the characteristic symptoms of Sydenham chorea.The exact underlying mechanisms that cause Sydenham chorea are poorly understood. Researchers believe that antigens (substances that are capable of stimulating an immune system response) on streptococcal bacterial cells are similar to antigens found on cells on the human body. When the immune system creates antibodies to combat the streptococcal infection, the antibodies also, in genetically predisposed individuals, mistakenly bind to healthy cells. When they bind to brain cells, they cause disruption in their “signaling” – their ability to control movement.
| 1,180 |
Sydenham Chorea
|
nord_1180_3
|
Affects of Sydenham Chorea
|
According to most studies, Sydenham chorea affects girls more often than boys. It usually develops in children between the ages of 5-15. Rarely, the disorder has been reported in children under age 5 years or in adults. Sydenham chorea affects individuals of all races and ethnicities.Sydenham chorea may occur as a complication of rheumatic fever. Approximately, 25 percent of individuals with rheumatic fever develop Sydenham chorea. The incidence of rheumatic fever in North America declined steadily in the past 50 years, although there have been occasional outbreaks. Sydenham chorea is the most common cause of acute chorea during childhood in the United States. In areas of the world with less access to medical care and antibiotics, rheumatic fever remains a major public health problem due primarily to cases where there is damage to heart valves.
|
Affects of Sydenham Chorea. According to most studies, Sydenham chorea affects girls more often than boys. It usually develops in children between the ages of 5-15. Rarely, the disorder has been reported in children under age 5 years or in adults. Sydenham chorea affects individuals of all races and ethnicities.Sydenham chorea may occur as a complication of rheumatic fever. Approximately, 25 percent of individuals with rheumatic fever develop Sydenham chorea. The incidence of rheumatic fever in North America declined steadily in the past 50 years, although there have been occasional outbreaks. Sydenham chorea is the most common cause of acute chorea during childhood in the United States. In areas of the world with less access to medical care and antibiotics, rheumatic fever remains a major public health problem due primarily to cases where there is damage to heart valves.
| 1,180 |
Sydenham Chorea
|
nord_1180_4
|
Related disorders of Sydenham Chorea
|
Symptoms of some other disorders can be similar to those of Sydenham chorea. While Sydenham chorea should be suspected as the most likely cause of acute chorea in children, there are other conditions doctors should consider as well.Many different disorders and conditions can be associated with acute chorea. In many developed countries, chorea is observed when psychiatric medications are started, increased, or stopped to abruptly. Specifically, abrupt withdrawal of antipsychotic /neuroleptic medications can cause chorea. These medications are prescribed for conditions such as schizophrenia, bipolar disorder, autism with irritability, and Tourette syndrome. Other medications such as stimulants used to treat ADHD or levodopa or anticholinergic medications can induce chorea when first started or if the dose is increased to a high level. Other acute choreas can be caused by autoimmune conditions. Examples include “anti-NMDA receptor encephalitis”, lupus, or some other rare autoimmune conditions. Some diseases related to metabolism or mitochondrial function can also cause chorea. Finally, there are also many rare neurological diseases which are chronic or degenerative which may include chorea as one symptom. Typically in these conditions neurologists recognize that the time course, other non-chorea symptoms, and neurological examination are different than Sydenham chorea. Examples include Huntington disease, neuroacanthocytosis, ataxia-telangiectasia, Wilson disease, and dentatorubral-pallidoluysian atrophy. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database, and be aware there is a much longer list of conditions associated with chorea.)
|
Related disorders of Sydenham Chorea. Symptoms of some other disorders can be similar to those of Sydenham chorea. While Sydenham chorea should be suspected as the most likely cause of acute chorea in children, there are other conditions doctors should consider as well.Many different disorders and conditions can be associated with acute chorea. In many developed countries, chorea is observed when psychiatric medications are started, increased, or stopped to abruptly. Specifically, abrupt withdrawal of antipsychotic /neuroleptic medications can cause chorea. These medications are prescribed for conditions such as schizophrenia, bipolar disorder, autism with irritability, and Tourette syndrome. Other medications such as stimulants used to treat ADHD or levodopa or anticholinergic medications can induce chorea when first started or if the dose is increased to a high level. Other acute choreas can be caused by autoimmune conditions. Examples include “anti-NMDA receptor encephalitis”, lupus, or some other rare autoimmune conditions. Some diseases related to metabolism or mitochondrial function can also cause chorea. Finally, there are also many rare neurological diseases which are chronic or degenerative which may include chorea as one symptom. Typically in these conditions neurologists recognize that the time course, other non-chorea symptoms, and neurological examination are different than Sydenham chorea. Examples include Huntington disease, neuroacanthocytosis, ataxia-telangiectasia, Wilson disease, and dentatorubral-pallidoluysian atrophy. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database, and be aware there is a much longer list of conditions associated with chorea.)
| 1,180 |
Sydenham Chorea
|
nord_1180_5
|
Diagnosis of Sydenham Chorea
|
A diagnosis of Sydenham chorea is made based upon identification of new onset choreic movements, a detailed patient history, and a thorough clinical evaluation. In the presence of new onset chorea, which is uncommon in childhood, the documentation of a prior streptococcal infection through throat swabs and/or the current presence of high blood titers of streptococcal antibodies (ASO, anti DNAseB) is useful, as are identification of co-occurring arthritis or cardiac valve abnormalities. In some cases, certain imaging techniques such as magnetic resonance imaging (MRI) may be recommended to exclude other causes. Usually, brain imaging is normal in Sydenham chorea. Of note, because the onset of Sydenham chorea usually occurs weeks after the infection, the characteristic signs of rheumatic fever or streptococcal infection are usually no longer present.Individuals who are diagnosed with Sydenham chorea should receive an evaluation for inflammation of the heart (carditis).
|
Diagnosis of Sydenham Chorea. A diagnosis of Sydenham chorea is made based upon identification of new onset choreic movements, a detailed patient history, and a thorough clinical evaluation. In the presence of new onset chorea, which is uncommon in childhood, the documentation of a prior streptococcal infection through throat swabs and/or the current presence of high blood titers of streptococcal antibodies (ASO, anti DNAseB) is useful, as are identification of co-occurring arthritis or cardiac valve abnormalities. In some cases, certain imaging techniques such as magnetic resonance imaging (MRI) may be recommended to exclude other causes. Usually, brain imaging is normal in Sydenham chorea. Of note, because the onset of Sydenham chorea usually occurs weeks after the infection, the characteristic signs of rheumatic fever or streptococcal infection are usually no longer present.Individuals who are diagnosed with Sydenham chorea should receive an evaluation for inflammation of the heart (carditis).
| 1,180 |
Sydenham Chorea
|
nord_1180_6
|
Therapies of Sydenham Chorea
|
Secondary Prevention
A confirmed diagnosis of Sydenham chorea is nearly always an indication for long-term antibiotic treatment, until adulthood. The purpose of this treatment is to prevent permanent heart valve damage which could result if the child experiences recurrent streptococcal infections. Most often penicillin is used. Physicians should consult current rheumatic fever guidelines.Chorea-suppressing Treatment
Chorea suppressing medications should be considered. Some mild cases may not cause much impairment for the child. These may resolve within weeks. When chorea symptoms are disabling, low doses of potent dopamine receptor blocking agents such as haloperidol, dopamine depleting agents such as tetrabenazine, anti-seizure medications such as valproic acid, or benzodiazepines may help. Because in most cases the treatment will only be needed for weeks to months and at low doses, long term neurological side effects such as tardive dyskinesia are extremely unlikely. Short term side effects such as weight gain may occur. As is the case for any neurological medications, however, a careful discussion of potential benefits as well as risks is advised.Immune system treatment
Additional short-term immune therapies have been used to treat individuals with impairing Sydenham chorea during the first weeks of symptoms, based on the idea that ongoing acute inflammation is contributing to symptoms. There is some scientific support for using oral steroids and intravenous immunoglobulins from small but rigorous clinical trials.
|
Therapies of Sydenham Chorea. Secondary Prevention
A confirmed diagnosis of Sydenham chorea is nearly always an indication for long-term antibiotic treatment, until adulthood. The purpose of this treatment is to prevent permanent heart valve damage which could result if the child experiences recurrent streptococcal infections. Most often penicillin is used. Physicians should consult current rheumatic fever guidelines.Chorea-suppressing Treatment
Chorea suppressing medications should be considered. Some mild cases may not cause much impairment for the child. These may resolve within weeks. When chorea symptoms are disabling, low doses of potent dopamine receptor blocking agents such as haloperidol, dopamine depleting agents such as tetrabenazine, anti-seizure medications such as valproic acid, or benzodiazepines may help. Because in most cases the treatment will only be needed for weeks to months and at low doses, long term neurological side effects such as tardive dyskinesia are extremely unlikely. Short term side effects such as weight gain may occur. As is the case for any neurological medications, however, a careful discussion of potential benefits as well as risks is advised.Immune system treatment
Additional short-term immune therapies have been used to treat individuals with impairing Sydenham chorea during the first weeks of symptoms, based on the idea that ongoing acute inflammation is contributing to symptoms. There is some scientific support for using oral steroids and intravenous immunoglobulins from small but rigorous clinical trials.
| 1,180 |
Sydenham Chorea
|
nord_1181_0
|
Overview of SYNGAP1-related NSID
|
SummaryIntellectual disability (ID) is a common disorder defined by the presence of significant limitations in both cognitive and adaptive behaviors with onset before the age of 18. ID is subdivided into syndromic intellectual disability, in which intellectual deficits and distinguishing morphologic, radiologic or metabolic features are present, and non-syndromic intellectual disability (NSID), in which intellectual deficits appear without these physical abnormalities. Mutations in the SYNGAP1 gene are thought to be a relatively common cause of NSID. NSID patients, including those associated with SYNGAP1 mutation, typically exhibit moderate to severe ID with varying degrees of epilepsy and/or autism spectrum disorders (ASD) and may also have attention deficits, impulsivity, and/or mood disorders. SYNGAP1-related NSID patients with epilepsy usually respond well to medications, yet some are refractory (difficult to control even with multiple drugs). SYNGAP1-related NSID is a sporadic condition that is caused by de novo (spontaneous, noninherited) mutations. The use of genomic sequencing has dramatically increased the capacity of physicians to identify these mutations.Introduction SYNGAP1-related NSID in humans was first reported in 2009 and is one of the first genes found to be associated with NSID. Since initially described, an increasing number of children with SYNGAP1-related NSID have been identified, suggesting that it may represent one of the most common causes of ID.
|
Overview of SYNGAP1-related NSID. SummaryIntellectual disability (ID) is a common disorder defined by the presence of significant limitations in both cognitive and adaptive behaviors with onset before the age of 18. ID is subdivided into syndromic intellectual disability, in which intellectual deficits and distinguishing morphologic, radiologic or metabolic features are present, and non-syndromic intellectual disability (NSID), in which intellectual deficits appear without these physical abnormalities. Mutations in the SYNGAP1 gene are thought to be a relatively common cause of NSID. NSID patients, including those associated with SYNGAP1 mutation, typically exhibit moderate to severe ID with varying degrees of epilepsy and/or autism spectrum disorders (ASD) and may also have attention deficits, impulsivity, and/or mood disorders. SYNGAP1-related NSID patients with epilepsy usually respond well to medications, yet some are refractory (difficult to control even with multiple drugs). SYNGAP1-related NSID is a sporadic condition that is caused by de novo (spontaneous, noninherited) mutations. The use of genomic sequencing has dramatically increased the capacity of physicians to identify these mutations.Introduction SYNGAP1-related NSID in humans was first reported in 2009 and is one of the first genes found to be associated with NSID. Since initially described, an increasing number of children with SYNGAP1-related NSID have been identified, suggesting that it may represent one of the most common causes of ID.
| 1,181 |
SYNGAP1-related NSID
|
nord_1181_1
|
Symptoms of SYNGAP1-related NSID
|
Children with SYNGAP1-related NSID present with mild hypotonia (low muscle tone) and global developmental delay at the end of the first year or during the second year of life. They can start to walk at a normal age but more frequently later in life (range: 14 months to 30 months of age). Rarely, their gait is described as being ataxic (unstable). Language development is also variably impaired with some children speaking with isolated words, associations of two or three words or with simple short sentences, whereas others remain non-verbal. Some of the children show oral dyspraxia (oral motor dysfunction), which can result in some drooling or eating difficulties.While the primary disorder with SYNGAP1-related NSID is moderate to severe cognitive impairment, a subset of children are also diagnosed with autism spectrum disorder (ASD). Other behavioral abnormalities include inattention, impulsivity, and physical aggression (hitting, biting). Mood swings, sullenness, and rigidity are also reported in many children.Approximately 2/3 of children with SYNGAP1-related NSID display epilepsy characterized by a variety of seizures including absences, myoclonia (brief, involuntary twitching of a group of muscles), generalized tonic-clonic seizures (grand mal seizures), and drop attacks. The seizures usually start during the first few years of life. Seizures are well controlled in most of the children with the administration of a single anti-epileptic drug but in some cases seizures are refractory.The appearance and the growth of children with SYNGAP1-related NSID are not unusual. Some of the children will develop microcephaly (smaller head circumference). The presence of this feature does not correlate with the severity of the cognitive impairment.Children (and presumably adults) with SYNGAP1-related NSID continue to develop, progressing at their own pace. Unless their epilepsy is not well controlled, they do not regress or deteriorate and can always continue to learn.
|
Symptoms of SYNGAP1-related NSID. Children with SYNGAP1-related NSID present with mild hypotonia (low muscle tone) and global developmental delay at the end of the first year or during the second year of life. They can start to walk at a normal age but more frequently later in life (range: 14 months to 30 months of age). Rarely, their gait is described as being ataxic (unstable). Language development is also variably impaired with some children speaking with isolated words, associations of two or three words or with simple short sentences, whereas others remain non-verbal. Some of the children show oral dyspraxia (oral motor dysfunction), which can result in some drooling or eating difficulties.While the primary disorder with SYNGAP1-related NSID is moderate to severe cognitive impairment, a subset of children are also diagnosed with autism spectrum disorder (ASD). Other behavioral abnormalities include inattention, impulsivity, and physical aggression (hitting, biting). Mood swings, sullenness, and rigidity are also reported in many children.Approximately 2/3 of children with SYNGAP1-related NSID display epilepsy characterized by a variety of seizures including absences, myoclonia (brief, involuntary twitching of a group of muscles), generalized tonic-clonic seizures (grand mal seizures), and drop attacks. The seizures usually start during the first few years of life. Seizures are well controlled in most of the children with the administration of a single anti-epileptic drug but in some cases seizures are refractory.The appearance and the growth of children with SYNGAP1-related NSID are not unusual. Some of the children will develop microcephaly (smaller head circumference). The presence of this feature does not correlate with the severity of the cognitive impairment.Children (and presumably adults) with SYNGAP1-related NSID continue to develop, progressing at their own pace. Unless their epilepsy is not well controlled, they do not regress or deteriorate and can always continue to learn.
| 1,181 |
SYNGAP1-related NSID
|
nord_1181_2
|
Causes of SYNGAP1-related NSID
|
The human genome is composed of approximately 20,000 genes. A great majority of these genes, including the SYNGAP1 gene, are expressed as two copies (one copy inherited from each parent). Only a single abnormal copy of the SYNGAP1 gene is sufficient to cause NSID (haploinsufficiency). The abnormal gene is usually the result of spontaneous mutation(s) (not inherited from either parent, also called de novo mutation). These new mutations occur spontaneously in the sperm or egg cells of one of the parents, without the influence of an environmental risk factor.The SYNGAP1 gene encodes for the protein, SynGAP (brain-specific RAS GTPase-activating). Normal levels of SynGAP protein are essential for proper brain function and development. Within the brain, the protein is most often found at synapses where it regulates critical biochemical signaling pathways that support learning and memory capabilities.
|
Causes of SYNGAP1-related NSID. The human genome is composed of approximately 20,000 genes. A great majority of these genes, including the SYNGAP1 gene, are expressed as two copies (one copy inherited from each parent). Only a single abnormal copy of the SYNGAP1 gene is sufficient to cause NSID (haploinsufficiency). The abnormal gene is usually the result of spontaneous mutation(s) (not inherited from either parent, also called de novo mutation). These new mutations occur spontaneously in the sperm or egg cells of one of the parents, without the influence of an environmental risk factor.The SYNGAP1 gene encodes for the protein, SynGAP (brain-specific RAS GTPase-activating). Normal levels of SynGAP protein are essential for proper brain function and development. Within the brain, the protein is most often found at synapses where it regulates critical biochemical signaling pathways that support learning and memory capabilities.
| 1,181 |
SYNGAP1-related NSID
|
nord_1181_3
|
Affects of SYNGAP1-related NSID
|
Intellectual disability caused by mutations in SYNGAP1 appears to be equally prevalent in males and females. The disorder is recognizable early during childhood. However, because affected children are generally healthy, this disorder may be as prevalent in the adult population as it is in children. SYNGAP1-related NSID is found in all ethnic groups, with the same prevalence.
|
Affects of SYNGAP1-related NSID. Intellectual disability caused by mutations in SYNGAP1 appears to be equally prevalent in males and females. The disorder is recognizable early during childhood. However, because affected children are generally healthy, this disorder may be as prevalent in the adult population as it is in children. SYNGAP1-related NSID is found in all ethnic groups, with the same prevalence.
| 1,181 |
SYNGAP1-related NSID
|
nord_1181_4
|
Related disorders of SYNGAP1-related NSID
|
There are several genetic forms of global developmental delay or intellectual disability that can mimic SYNGAP1-related NSID. Distinguishing them on a clinical basis is difficult without genetic testing.
|
Related disorders of SYNGAP1-related NSID. There are several genetic forms of global developmental delay or intellectual disability that can mimic SYNGAP1-related NSID. Distinguishing them on a clinical basis is difficult without genetic testing.
| 1,181 |
SYNGAP1-related NSID
|
nord_1181_5
|
Diagnosis of SYNGAP1-related NSID
|
Children with moderate to severe non-syndromic global developmental delay (GDD) or ID should be genetically screened for potential involvement of genes. The presence of a generalized form of epilepsy (recognizable by physicians by the type of seizures and the EEG pattern) is consistent with the diagnosis. Microcephaly, when present, is not congenital but acquired. Brain imaging techniques such as MRI usually do not show any specific neural abnormalities.Because such a clinical presentation is common and associated with numerous genes, specific genetic testing for mutations in SYNGAP1 results in a low yield. More recently, physicians are requesting genomic testing (the exploration of all genes at once) for the investigation of children with GDD/ID. By exploring the whole genome in this way, physicians aim to increase their chance of finding the gene causing their patient’s disorder. They usually start with a genome-wide search for deletions or duplications that encompass single or multiple genes using array hybridization. If this analysis does not yield answers, the next step could be the sequencing of all the genes (whole-exome or whole-genome sequencing).
|
Diagnosis of SYNGAP1-related NSID. Children with moderate to severe non-syndromic global developmental delay (GDD) or ID should be genetically screened for potential involvement of genes. The presence of a generalized form of epilepsy (recognizable by physicians by the type of seizures and the EEG pattern) is consistent with the diagnosis. Microcephaly, when present, is not congenital but acquired. Brain imaging techniques such as MRI usually do not show any specific neural abnormalities.Because such a clinical presentation is common and associated with numerous genes, specific genetic testing for mutations in SYNGAP1 results in a low yield. More recently, physicians are requesting genomic testing (the exploration of all genes at once) for the investigation of children with GDD/ID. By exploring the whole genome in this way, physicians aim to increase their chance of finding the gene causing their patient’s disorder. They usually start with a genome-wide search for deletions or duplications that encompass single or multiple genes using array hybridization. If this analysis does not yield answers, the next step could be the sequencing of all the genes (whole-exome or whole-genome sequencing).
| 1,181 |
SYNGAP1-related NSID
|
nord_1181_6
|
Therapies of SYNGAP1-related NSID
|
Clinical Testing and Workup
Genetic testing provides definitive diagnosis of SYNGAP1-related NISD. Medical assessment for the possibility of seizures, swallowing difficulties, ASD and other behavioral abnormalities is recommended. Because brain MRI does not typically show any abnormality in these children, it is not formally indicated to perform this exam. Neurologists, however, may request a brain MRI in children with seizures. The recommended evaluations for a child diagnosed with SYNGAP1-related NSID are summarized in the Management section of the following resource:
https://www.ncbi.nlm.nih.gov/books/NBK537721/Treatment
Like other forms of intellectual disability, there are no known disease-altering treatments for SYNGAP1-related disorders. Current treatment for NSID in general is directed toward the specific symptoms that are apparent in each individual. Management may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, pediatric neurologists, gastroenterologists, psychiatrists, speech pathologists, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.
Treatment options that may be used to treat individuals with an ID are complex and varied. The specific treatment plan will need to be highly individualized. Decisions concerning the use of specific treatments should be made by physicians and other members of the health care team in careful consultation with an affected child’s parents or with an adult patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Early developmental intervention is important to ensure that affected children reach their potential. Most affected children will benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. It is essential that therapies are continued on a year-round basis to promote development of new skills and to prevent regression. Additional medical, social and/or vocational services including special remedial education may be necessary. Psychosocial support for the entire family is essential as well. Other treatment is symptomatic and supportive. Additional therapies for an NSID syndrome depend upon the specific abnormalities present and generally follow standard guidelines. Anti-seizure medications are usually effective in treating seizures for those patients that present with epilepsy; however, in a subset of patients, these medications do not work (refractory seizures) requiring non-pharmacologic treatments such as epilepsy surgery or neurostimulation.Genetic counseling is recommended for affected individuals and their families.
|
Therapies of SYNGAP1-related NSID. Clinical Testing and Workup
Genetic testing provides definitive diagnosis of SYNGAP1-related NISD. Medical assessment for the possibility of seizures, swallowing difficulties, ASD and other behavioral abnormalities is recommended. Because brain MRI does not typically show any abnormality in these children, it is not formally indicated to perform this exam. Neurologists, however, may request a brain MRI in children with seizures. The recommended evaluations for a child diagnosed with SYNGAP1-related NSID are summarized in the Management section of the following resource:
https://www.ncbi.nlm.nih.gov/books/NBK537721/Treatment
Like other forms of intellectual disability, there are no known disease-altering treatments for SYNGAP1-related disorders. Current treatment for NSID in general is directed toward the specific symptoms that are apparent in each individual. Management may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, pediatric neurologists, gastroenterologists, psychiatrists, speech pathologists, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.
Treatment options that may be used to treat individuals with an ID are complex and varied. The specific treatment plan will need to be highly individualized. Decisions concerning the use of specific treatments should be made by physicians and other members of the health care team in careful consultation with an affected child’s parents or with an adult patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Early developmental intervention is important to ensure that affected children reach their potential. Most affected children will benefit from occupational, physical and speech therapy. Various methods of rehabilitative and behavioral therapy may be beneficial. It is essential that therapies are continued on a year-round basis to promote development of new skills and to prevent regression. Additional medical, social and/or vocational services including special remedial education may be necessary. Psychosocial support for the entire family is essential as well. Other treatment is symptomatic and supportive. Additional therapies for an NSID syndrome depend upon the specific abnormalities present and generally follow standard guidelines. Anti-seizure medications are usually effective in treating seizures for those patients that present with epilepsy; however, in a subset of patients, these medications do not work (refractory seizures) requiring non-pharmacologic treatments such as epilepsy surgery or neurostimulation.Genetic counseling is recommended for affected individuals and their families.
| 1,181 |
SYNGAP1-related NSID
|
nord_1182_0
|
Overview of Syphilis, Acquired
|
Syphilis is a chronic infectious disease caused by the bacterium (microorganism) treponema pallidum. It is transmitted by direct contact with an infected lesion, usually through sexual intercourse. When untreated, syphilis progresses through primary, secondary and latent stages. The early stages of syphilis may not have any detectable symptoms. In some cases, symptoms can remain dormant for years. Eventually any tissue or vascular organ in the body may be affected.Syphilis may also be acquired by the fetus in the uterus (congenital syphilis). Syphilis, especially when detected early, may be cured with appropriate treatment.
|
Overview of Syphilis, Acquired. Syphilis is a chronic infectious disease caused by the bacterium (microorganism) treponema pallidum. It is transmitted by direct contact with an infected lesion, usually through sexual intercourse. When untreated, syphilis progresses through primary, secondary and latent stages. The early stages of syphilis may not have any detectable symptoms. In some cases, symptoms can remain dormant for years. Eventually any tissue or vascular organ in the body may be affected.Syphilis may also be acquired by the fetus in the uterus (congenital syphilis). Syphilis, especially when detected early, may be cured with appropriate treatment.
| 1,182 |
Syphilis, Acquired
|
nord_1182_1
|
Symptoms of Syphilis, Acquired
|
Untreated syphilis progresses through primary and secondary stages (which are infectious), and may end without further symptoms or continue to progress into a latent stage that may last for years.Primary syphilis is characterized by lesions (chancres) of the skin, anus, vagina or moist surface of the mouth. These lesions present themselves from 10 to 90 days after an individual has been exposed to the organism and are found at the sight of contact with the infected person. The lesions are usually painless and start as small, solid elevations (papules) of the skin that gradually develop into raised, firm ulcers with a slight yellow discharge. When untreated, these lesions heal within four to six weeks and may leave scarring.Secondary syphilis usually presents itself within two weeks to six months after the appearance of the primary lesions. This stage of the disorder is characterized by lesions of the skin and mucous membranes that may be pink or coppery in color, widespread, symmetrical, and follow the lines of skin cleavage. The skin lesions of secondary syphilis are infectious and most often found on the genitalia, palms, and soles of the feet. Symptoms such as loss of appetite, sore throat, headache, low-grade fever, muscle aches, nasal discharge, and swollen lymph nodes may occur. There is a relapse in 25 percent of the untreated cases, occurring most often in the first year. Secondary syphilis usually lasts two to six weeks and some of the lesions may leave scarring.Latent syphilis occurs when primary and secondary syphilis have gone untreated. There are no noticeable symptoms, and the diagnosis can only be made through laboratory tests. Affected individuals are not contagious during this stage. However, they may relapse during the first two to four years of infection, and infectious secondary syphilis lesions may reappear. In about one third of the cases the disease spontaneously cures itself. Another third will remain infected but show no signs of the disease (asymptomatic). The final third will eventually develop late syphilis.Late syphilis, also known as tertiary syphilis, is not contagious and usually progresses slowly. Benign (non-contagious) tumors may develop on any part of the body. These tumors usually involve the skin and bones. Heart disease (cardiovascular problems), seizures, mental illness, personality changes, impotence, bladder dysfunction, and eye problems such as degeneration of the optic nerve of the eye (optic atrophy) and the development of Argyll Robertson pupils (pupils that fail to react to light but still react to distance) may also be present with late syphilis. Dementia and blindness may eventually result.In approximately three to seven percent of cases, affected individuals may develop neurosyphilis during the early stages of syphilis. Neurosyphilis occurs when the syphilis bacteria spread to the central nervous system. Affected individuals may not develop any associated symptoms. In some cases, individuals will experience seizures, headaches, fevers, stiff neck, dementia, and behavioral abnormalities.
|
Symptoms of Syphilis, Acquired. Untreated syphilis progresses through primary and secondary stages (which are infectious), and may end without further symptoms or continue to progress into a latent stage that may last for years.Primary syphilis is characterized by lesions (chancres) of the skin, anus, vagina or moist surface of the mouth. These lesions present themselves from 10 to 90 days after an individual has been exposed to the organism and are found at the sight of contact with the infected person. The lesions are usually painless and start as small, solid elevations (papules) of the skin that gradually develop into raised, firm ulcers with a slight yellow discharge. When untreated, these lesions heal within four to six weeks and may leave scarring.Secondary syphilis usually presents itself within two weeks to six months after the appearance of the primary lesions. This stage of the disorder is characterized by lesions of the skin and mucous membranes that may be pink or coppery in color, widespread, symmetrical, and follow the lines of skin cleavage. The skin lesions of secondary syphilis are infectious and most often found on the genitalia, palms, and soles of the feet. Symptoms such as loss of appetite, sore throat, headache, low-grade fever, muscle aches, nasal discharge, and swollen lymph nodes may occur. There is a relapse in 25 percent of the untreated cases, occurring most often in the first year. Secondary syphilis usually lasts two to six weeks and some of the lesions may leave scarring.Latent syphilis occurs when primary and secondary syphilis have gone untreated. There are no noticeable symptoms, and the diagnosis can only be made through laboratory tests. Affected individuals are not contagious during this stage. However, they may relapse during the first two to four years of infection, and infectious secondary syphilis lesions may reappear. In about one third of the cases the disease spontaneously cures itself. Another third will remain infected but show no signs of the disease (asymptomatic). The final third will eventually develop late syphilis.Late syphilis, also known as tertiary syphilis, is not contagious and usually progresses slowly. Benign (non-contagious) tumors may develop on any part of the body. These tumors usually involve the skin and bones. Heart disease (cardiovascular problems), seizures, mental illness, personality changes, impotence, bladder dysfunction, and eye problems such as degeneration of the optic nerve of the eye (optic atrophy) and the development of Argyll Robertson pupils (pupils that fail to react to light but still react to distance) may also be present with late syphilis. Dementia and blindness may eventually result.In approximately three to seven percent of cases, affected individuals may develop neurosyphilis during the early stages of syphilis. Neurosyphilis occurs when the syphilis bacteria spread to the central nervous system. Affected individuals may not develop any associated symptoms. In some cases, individuals will experience seizures, headaches, fevers, stiff neck, dementia, and behavioral abnormalities.
| 1,182 |
Syphilis, Acquired
|
nord_1182_2
|
Causes of Syphilis, Acquired
|
Syphilis is caused by a bacterium (microorganism) known as treponema pallidum and acquired through sexual contact with an infected person. On rare occasions, health workers have become infected while examining affected individuals with infectious lesions. It may also be acquired by kissing someone with oral infectious lesions. Infected mothers can transmit syphilis to the fetus in the womb, a condition known as congenital syphilis. (For more information on this disorder choose “congenital syphilis” as your search term in the Rare Disease Database.)
|
Causes of Syphilis, Acquired. Syphilis is caused by a bacterium (microorganism) known as treponema pallidum and acquired through sexual contact with an infected person. On rare occasions, health workers have become infected while examining affected individuals with infectious lesions. It may also be acquired by kissing someone with oral infectious lesions. Infected mothers can transmit syphilis to the fetus in the womb, a condition known as congenital syphilis. (For more information on this disorder choose “congenital syphilis” as your search term in the Rare Disease Database.)
| 1,182 |
Syphilis, Acquired
|
nord_1182_3
|
Affects of Syphilis, Acquired
|
There are about 80,000 cases of syphilis reported each year in the United States. The highest rate of syphilis is among 20 to 24 year old men and women. Syphilis is more common in the southern states of the United States. It is more common among persons who have sexual contact with numerous partners.The male to female ratio of syphilis is 3:1. In recent years, the rates of syphilis have declined in the United States. Syphilis occurs with higher rates in developing countries, although developed countries experience outbreaks.In 1998, the incidence of syphilis was 2.6 cases per 100,000 people in the United States, a lower rate than in 1997 when there were 3.2 cases per 100,000 people. The US Centers for Disease Control and Prevention (CDC) is working toward eliminating syphilis and plans to reduce the incidence of syphilis to fewer than 1,000 cases in the United States by the year 2005. In 2002, the CDC reported that the number of cases of syphilis in the United States rose from 5, 979 in 2000 to 6,103 in 2001, the first increase since 1990.
|
Affects of Syphilis, Acquired. There are about 80,000 cases of syphilis reported each year in the United States. The highest rate of syphilis is among 20 to 24 year old men and women. Syphilis is more common in the southern states of the United States. It is more common among persons who have sexual contact with numerous partners.The male to female ratio of syphilis is 3:1. In recent years, the rates of syphilis have declined in the United States. Syphilis occurs with higher rates in developing countries, although developed countries experience outbreaks.In 1998, the incidence of syphilis was 2.6 cases per 100,000 people in the United States, a lower rate than in 1997 when there were 3.2 cases per 100,000 people. The US Centers for Disease Control and Prevention (CDC) is working toward eliminating syphilis and plans to reduce the incidence of syphilis to fewer than 1,000 cases in the United States by the year 2005. In 2002, the CDC reported that the number of cases of syphilis in the United States rose from 5, 979 in 2000 to 6,103 in 2001, the first increase since 1990.
| 1,182 |
Syphilis, Acquired
|
nord_1182_4
|
Related disorders of Syphilis, Acquired
|
Symptoms of the following disorders can be similar to those of Acquired Syphilis. Comparisons may be useful for a differential diagnosis:Behcet's syndrome is a relapsing inflammatory disease with unknown cause. The most common symptoms include oral and genital ulcers and inflammation of the eyes. The joints, blood vessels, central nervous system, and gastrointestinal tract may also be involved. Attacks may last a week to a month and recur spontaneously. Behcet's syndrome is not a venereal disease. (For more information on this disorder, choose “Behcet” as your search term in the Rare Disease Database.)Bejel, or endemic syphilis, is an infectious disease caused by an organism (treponema pallidum II) related to and identical in appearance to that causing venereal syphilis. This infection causes lesions of the skin and bone and is common among children in the mediterranean countries of the Middle East, northern Africa, parts of eastern Europe, Arabia, subsaharan Africa, and Southeast Asia. In the United States, however, it is rare. Bejel is transmitted by physical, nonsexual contact and the sharing of eating and drinking utensils. (For more information on this disease choose “Bejel” as your search term in the Rare Disease Database.)Candidiasis (Candida Albicans) is a normally harmless yeast infection found in the mouth, intestinal tract, and vagina. This disorder is an infection caused by a fungus called candida, most commonly the Candida Albicans variety. It is also known as a yeast infection and it usually affects the skin and/or the mucous membranes of the mouth, intestines, or the vagina. Candida infections are rarely serious in otherwise healthy people. In rare cases it may spread through other parts of the body if the patients immune system is not functioning properly. In severe cases it may affect the blood, the membrane lining the heart muscle, or membranes around the brain (meninges). (For more information on this disorder, choose “Candidiasis” as your search term in the Rare Disease Database.)Chancroid is a sexually transmitted infection caused by the bacillus Hemophilus ducreyi. The incubation period for this disease is two to fourteen days. Chancroid affects the skin and starts as an inflamed patch of skin which eventually becomes a painful ulcer. Lesions are usually single but may be multiple. In males these lesions are usually found on the penis or around the anus. The lesions on females are normally found on the vagina, cervix, vulva, or around the anus. This infection is rare in the United States but common in Africa and Southeast Asia. Chancroid is usually treated with the antibiotic erythromycin.Congenital syphilis is a chronic infectious disease caused by a microorganism (treponema pallidum) acquired by the fetus in the uterus or before birth. Symptoms of early congenital syphilis include fever, skin problems and low birth weight. In late congenital syphilis the symptoms of the disease do not usually become apparent until two to five years of age. In rare cases the disease may remain latent for years with symptoms not being diagnosed until well into adulthood. Symptoms of congenital syphilis may include inflammation and hardening of the umbilical chord, rash, fever, low birth weight, high levels of cholesterol at birth, aseptic meningitis, anemia, enlarged liver and spleen, jaundice (yellowish color of the skin), shedding of skin affecting the palms and soles, convulsions, mental retardation, inflammation around the bones, nasal discharge, hair loss, inflammation of the eye's iris, and pneumonia. (For more information on congenital syphilis choose “Syphilis, Congenital” as your search term in the Rare Disease Database.)Herpes progenitalis is an infection of the genital skin caused by the herpes simplex virus. This infection is spread through sexual contact and lesions may appear within 4 to 7 days after contact. These lesions start out as blisters and may have a watery discharge. Both men and women may experience headaches, muscle aches and tender swollen lymph nodes in the groin. The blisters crust over and heal without treatment. Symptoms may last about 3 weeks. The disorder is contagious for up to two weeks after the lesions appear. The virus may remain latent and then reoccur at any time. There is no cure for this infection but lotions may be used to relieve pain, and the drug Acyclovir may prevent recurrent attacks.Pinta is an infectious disease caused by the microorganism treponema carateum. It is closely related to the microorganism which causes some other venereal diseases. Pinta is transmitted nonsexually and is characterized by rashes and discoloration of the skin. Small bumps develop and within several months reddish, scaly areas appear most often on the face, hands, and feet. It is common in the hot lowlands of Central and South America, but is rare in the United States. (For more information on this disease choose “Pinta” as your search term in the Rare Disease Database)Yaws is a nonvenereal infectious disease caused by the microorganism treponema pertenue which is related to syphilis. This disorder is common in children and is characterized by skin and bone lesions. Yaws is rarely found in the United States but is common among children in the humid tropics of Africa, South and Central America, the West Indies, and the Far East. (For more information on this disease choose “Yaws” as your search term in the Rare Disease Database.)
|
Related disorders of Syphilis, Acquired. Symptoms of the following disorders can be similar to those of Acquired Syphilis. Comparisons may be useful for a differential diagnosis:Behcet's syndrome is a relapsing inflammatory disease with unknown cause. The most common symptoms include oral and genital ulcers and inflammation of the eyes. The joints, blood vessels, central nervous system, and gastrointestinal tract may also be involved. Attacks may last a week to a month and recur spontaneously. Behcet's syndrome is not a venereal disease. (For more information on this disorder, choose “Behcet” as your search term in the Rare Disease Database.)Bejel, or endemic syphilis, is an infectious disease caused by an organism (treponema pallidum II) related to and identical in appearance to that causing venereal syphilis. This infection causes lesions of the skin and bone and is common among children in the mediterranean countries of the Middle East, northern Africa, parts of eastern Europe, Arabia, subsaharan Africa, and Southeast Asia. In the United States, however, it is rare. Bejel is transmitted by physical, nonsexual contact and the sharing of eating and drinking utensils. (For more information on this disease choose “Bejel” as your search term in the Rare Disease Database.)Candidiasis (Candida Albicans) is a normally harmless yeast infection found in the mouth, intestinal tract, and vagina. This disorder is an infection caused by a fungus called candida, most commonly the Candida Albicans variety. It is also known as a yeast infection and it usually affects the skin and/or the mucous membranes of the mouth, intestines, or the vagina. Candida infections are rarely serious in otherwise healthy people. In rare cases it may spread through other parts of the body if the patients immune system is not functioning properly. In severe cases it may affect the blood, the membrane lining the heart muscle, or membranes around the brain (meninges). (For more information on this disorder, choose “Candidiasis” as your search term in the Rare Disease Database.)Chancroid is a sexually transmitted infection caused by the bacillus Hemophilus ducreyi. The incubation period for this disease is two to fourteen days. Chancroid affects the skin and starts as an inflamed patch of skin which eventually becomes a painful ulcer. Lesions are usually single but may be multiple. In males these lesions are usually found on the penis or around the anus. The lesions on females are normally found on the vagina, cervix, vulva, or around the anus. This infection is rare in the United States but common in Africa and Southeast Asia. Chancroid is usually treated with the antibiotic erythromycin.Congenital syphilis is a chronic infectious disease caused by a microorganism (treponema pallidum) acquired by the fetus in the uterus or before birth. Symptoms of early congenital syphilis include fever, skin problems and low birth weight. In late congenital syphilis the symptoms of the disease do not usually become apparent until two to five years of age. In rare cases the disease may remain latent for years with symptoms not being diagnosed until well into adulthood. Symptoms of congenital syphilis may include inflammation and hardening of the umbilical chord, rash, fever, low birth weight, high levels of cholesterol at birth, aseptic meningitis, anemia, enlarged liver and spleen, jaundice (yellowish color of the skin), shedding of skin affecting the palms and soles, convulsions, mental retardation, inflammation around the bones, nasal discharge, hair loss, inflammation of the eye's iris, and pneumonia. (For more information on congenital syphilis choose “Syphilis, Congenital” as your search term in the Rare Disease Database.)Herpes progenitalis is an infection of the genital skin caused by the herpes simplex virus. This infection is spread through sexual contact and lesions may appear within 4 to 7 days after contact. These lesions start out as blisters and may have a watery discharge. Both men and women may experience headaches, muscle aches and tender swollen lymph nodes in the groin. The blisters crust over and heal without treatment. Symptoms may last about 3 weeks. The disorder is contagious for up to two weeks after the lesions appear. The virus may remain latent and then reoccur at any time. There is no cure for this infection but lotions may be used to relieve pain, and the drug Acyclovir may prevent recurrent attacks.Pinta is an infectious disease caused by the microorganism treponema carateum. It is closely related to the microorganism which causes some other venereal diseases. Pinta is transmitted nonsexually and is characterized by rashes and discoloration of the skin. Small bumps develop and within several months reddish, scaly areas appear most often on the face, hands, and feet. It is common in the hot lowlands of Central and South America, but is rare in the United States. (For more information on this disease choose “Pinta” as your search term in the Rare Disease Database)Yaws is a nonvenereal infectious disease caused by the microorganism treponema pertenue which is related to syphilis. This disorder is common in children and is characterized by skin and bone lesions. Yaws is rarely found in the United States but is common among children in the humid tropics of Africa, South and Central America, the West Indies, and the Far East. (For more information on this disease choose “Yaws” as your search term in the Rare Disease Database.)
| 1,182 |
Syphilis, Acquired
|
nord_1182_5
|
Diagnosis of Syphilis, Acquired
|
A diagnosis of syphilis, which is often difficult because of mild or absent symptoms in early states, is made based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic symptoms. Blood tests may be used to confirm a diagnosis of syphilis, but may be difficult to interpret and often give false negative results. A physician may also obtain a small sample of tissue by scraping an ulcer or rash for microscopic study in order to determine the presence of the syphilis bacteria.
|
Diagnosis of Syphilis, Acquired. A diagnosis of syphilis, which is often difficult because of mild or absent symptoms in early states, is made based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic symptoms. Blood tests may be used to confirm a diagnosis of syphilis, but may be difficult to interpret and often give false negative results. A physician may also obtain a small sample of tissue by scraping an ulcer or rash for microscopic study in order to determine the presence of the syphilis bacteria.
| 1,182 |
Syphilis, Acquired
|
nord_1182_6
|
Therapies of Syphilis, Acquired
|
TreatmentAntibiotics are used to treat acquired syphilis. Penicillin is the treatment used most often. Some individuals do not respond to therapy with penicillin, and periodic blood tests to confirm the absence of syphilis is recommended.In some cases, other antibiotics such as tetracycline or erythromycin may be used. Preventative treatment should be given to anyone who has been in sexual contact with an infected person within 90 days. It is very important that an affected individual’s history (especially sexual) be taken, and a battery of tests performed, in order to determine the stage of syphilis present.
|
Therapies of Syphilis, Acquired. TreatmentAntibiotics are used to treat acquired syphilis. Penicillin is the treatment used most often. Some individuals do not respond to therapy with penicillin, and periodic blood tests to confirm the absence of syphilis is recommended.In some cases, other antibiotics such as tetracycline or erythromycin may be used. Preventative treatment should be given to anyone who has been in sexual contact with an infected person within 90 days. It is very important that an affected individual’s history (especially sexual) be taken, and a battery of tests performed, in order to determine the stage of syphilis present.
| 1,182 |
Syphilis, Acquired
|
nord_1183_0
|
Overview of Syringobulbia
|
Syringobulbia is a neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord that extends to involve the brainstem (medulla). It usually occurs as a slit-like gap within the lower brainstem that may affect one or more of the cranial nerves, causing facial palsies of various kinds. In addition, sensory and motor nerve pathways may be affected by compression and/or interruption. This disorder is intimately associated with syringomyelia, in which the syrinx is limited to the spinal cord, and to the Chiari I malformation.
|
Overview of Syringobulbia. Syringobulbia is a neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord that extends to involve the brainstem (medulla). It usually occurs as a slit-like gap within the lower brainstem that may affect one or more of the cranial nerves, causing facial palsies of various kinds. In addition, sensory and motor nerve pathways may be affected by compression and/or interruption. This disorder is intimately associated with syringomyelia, in which the syrinx is limited to the spinal cord, and to the Chiari I malformation.
| 1,183 |
Syringobulbia
|
nord_1183_1
|
Symptoms of Syringobulbia
|
Usually, syringobulbia presents after syringomyelia, although isolated cases of syringobulbia have been documented. Syringobulbia is a slowly progressive disorder that may cause dizziness (vertigo), involuntary rapid movement of the eyeball (nystagmus), and loss of feelings of pain and temperature in the face. Atrophy and small local involuntary contractions (fibrillation) of the tongue muscle may also occur, as well as stuttering (dysphonia), and a shrill or harsh voice. Symptoms may also include impaired vision, numbness, and an unsteady way of walking (gait instability).Other symptoms may include hearing loss or ringing in the ears (tinnitus) and periodic limb movements. In rare cases, nausea, vomiting, and feeding difficulties may be early symptoms.
|
Symptoms of Syringobulbia. Usually, syringobulbia presents after syringomyelia, although isolated cases of syringobulbia have been documented. Syringobulbia is a slowly progressive disorder that may cause dizziness (vertigo), involuntary rapid movement of the eyeball (nystagmus), and loss of feelings of pain and temperature in the face. Atrophy and small local involuntary contractions (fibrillation) of the tongue muscle may also occur, as well as stuttering (dysphonia), and a shrill or harsh voice. Symptoms may also include impaired vision, numbness, and an unsteady way of walking (gait instability).Other symptoms may include hearing loss or ringing in the ears (tinnitus) and periodic limb movements. In rare cases, nausea, vomiting, and feeding difficulties may be early symptoms.
| 1,183 |
Syringobulbia
|
nord_1183_2
|
Causes of Syringobulbia
|
The cause of Syringobulbia is unknown. The disorder is usually present from birth.
|
Causes of Syringobulbia. The cause of Syringobulbia is unknown. The disorder is usually present from birth.
| 1,183 |
Syringobulbia
|
nord_1183_3
|
Affects of Syringobulbia
|
Syringobulbia can affect people of either sex. It usually is apparent before 30 years of age. In one study of a pediatric population, the average age of onset of symptoms was just under 15 years of age.
|
Affects of Syringobulbia. Syringobulbia can affect people of either sex. It usually is apparent before 30 years of age. In one study of a pediatric population, the average age of onset of symptoms was just under 15 years of age.
| 1,183 |
Syringobulbia
|
nord_1183_4
|
Related disorders of Syringobulbia
|
Syringomyelia is a neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord. The cavity is a congenital lesion, but for unknown reasons it often expands during adolescence or the young adult years. The syrinx is situated near the middle of the spine. It usually begins in the neck (cervical) area, but may extend to almost its whole length. (For more information on this disorder, choose “Syringomyelia” as your search term in the Rare Disease Database.)Amyloid neuropathy is a hereditary disorder in which an abnormal glycoprotein, called amyloid, accumulates in the nervous system in amounts sufficient to impair its function. It often affects the elderly. (For more information on this disorder, choose “Amyloidosis” as your search term in the Rare Disease Database.)Arnold-Chiari malformation is a rare malformation of the brain that is present at birth and characterized by the downward displacement of the lower brainstem into the spinal canal. (For more information on this disorder, choose “Arnold-Chiari” as your search term in the Rare Disease Database.)Neoplasms and vascular malformations in the brainstem may also cause neurological symptoms similar to those of syringobulbia.
|
Related disorders of Syringobulbia. Syringomyelia is a neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord. The cavity is a congenital lesion, but for unknown reasons it often expands during adolescence or the young adult years. The syrinx is situated near the middle of the spine. It usually begins in the neck (cervical) area, but may extend to almost its whole length. (For more information on this disorder, choose “Syringomyelia” as your search term in the Rare Disease Database.)Amyloid neuropathy is a hereditary disorder in which an abnormal glycoprotein, called amyloid, accumulates in the nervous system in amounts sufficient to impair its function. It often affects the elderly. (For more information on this disorder, choose “Amyloidosis” as your search term in the Rare Disease Database.)Arnold-Chiari malformation is a rare malformation of the brain that is present at birth and characterized by the downward displacement of the lower brainstem into the spinal canal. (For more information on this disorder, choose “Arnold-Chiari” as your search term in the Rare Disease Database.)Neoplasms and vascular malformations in the brainstem may also cause neurological symptoms similar to those of syringobulbia.
| 1,183 |
Syringobulbia
|
nord_1183_5
|
Diagnosis of Syringobulbia
|
The diagnosis of syringobulbia is made by means of neuroimaging, typically magnetic resonance imaging (MRI).
|
Diagnosis of Syringobulbia. The diagnosis of syringobulbia is made by means of neuroimaging, typically magnetic resonance imaging (MRI).
| 1,183 |
Syringobulbia
|
nord_1183_6
|
Therapies of Syringobulbia
|
TreatmentTreatment of syringobulbia is almost invariably surgical and consists of efforts to reroute the flow of cerebrospinal fluid by the use of diversion tubes or shunts. The various surgical approaches for syringobulbia usually must be combine with treatment for syringomyelia.
|
Therapies of Syringobulbia. TreatmentTreatment of syringobulbia is almost invariably surgical and consists of efforts to reroute the flow of cerebrospinal fluid by the use of diversion tubes or shunts. The various surgical approaches for syringobulbia usually must be combine with treatment for syringomyelia.
| 1,183 |
Syringobulbia
|
nord_1184_0
|
Overview of Syringomyelia
|
SummarySyringomyelia is a condition characterized by a fluid-filled cavity or cyst known as a syrinx that forms within the spinal cord. Syringomyelia is a chronic condition and a syrinx can expand over time compressing or destroying the surrounding nerve tissue. A wide variety of symptoms can potentially be associated with syringomyelia depending upon the size and exact location of the syrinx. Common signs/symptoms include pain in the neck and shoulders, muscle weakness, pain and stiffness in the legs, numbness or decreased sensation, especially to hot and cold, abnormal curvature of the spine (scoliosis), muscle contractions, and uncoordinated movements (ataxia). The majority of cases of syringomyelia are associated with a complex brain abnormality known as a Chiari malformation. Additional known causes of syringomyelia include tethered cord syndrome, meningitis (arachnoiditis), certain tumors of the spinal cord, and trauma. In some patients, no underlying cause can be identified (idiopathic).IntroductionThe terminology used in the medical literature to describe syringomyelia can be confusing. Syringomyelia is often associated with an abnormality of the craniovertebral junction, usually a Chiari malformation (types I and II), and these cases may be referred to as congenital syringomyelia. Secondary syringomyelia refers to cases that have a known cause. The term primary syringomyelia has been used to refer to cases of unknown cause or to cases that occur because of specific known causes that damage the spinal cord. Posttraumatic syringomyelia refers to cases that result from trauma to the spinal cord (these cases are sometimes sub-classified as primary syringomyelia).Some individuals have a condition related to syringomyelia known as hydro(syringo)myelia, which is characterized by abnormal widening of the central canal of the spinal cord (the normal small canal running through the center of the spinal cord). Some physicians use the terms syringomyelia or hydromyelia interchangeably. Hydromyelia may also be present in infants and young children with or without brain abnormalities, such as Chiari malformation type II that is seen in patients with spina bifida. The fluid-filled cavities in cases of syringomyelia often do not connect to any other fluid-filled areas or spaces and occur more often in adults than children.
|
Overview of Syringomyelia. SummarySyringomyelia is a condition characterized by a fluid-filled cavity or cyst known as a syrinx that forms within the spinal cord. Syringomyelia is a chronic condition and a syrinx can expand over time compressing or destroying the surrounding nerve tissue. A wide variety of symptoms can potentially be associated with syringomyelia depending upon the size and exact location of the syrinx. Common signs/symptoms include pain in the neck and shoulders, muscle weakness, pain and stiffness in the legs, numbness or decreased sensation, especially to hot and cold, abnormal curvature of the spine (scoliosis), muscle contractions, and uncoordinated movements (ataxia). The majority of cases of syringomyelia are associated with a complex brain abnormality known as a Chiari malformation. Additional known causes of syringomyelia include tethered cord syndrome, meningitis (arachnoiditis), certain tumors of the spinal cord, and trauma. In some patients, no underlying cause can be identified (idiopathic).IntroductionThe terminology used in the medical literature to describe syringomyelia can be confusing. Syringomyelia is often associated with an abnormality of the craniovertebral junction, usually a Chiari malformation (types I and II), and these cases may be referred to as congenital syringomyelia. Secondary syringomyelia refers to cases that have a known cause. The term primary syringomyelia has been used to refer to cases of unknown cause or to cases that occur because of specific known causes that damage the spinal cord. Posttraumatic syringomyelia refers to cases that result from trauma to the spinal cord (these cases are sometimes sub-classified as primary syringomyelia).Some individuals have a condition related to syringomyelia known as hydro(syringo)myelia, which is characterized by abnormal widening of the central canal of the spinal cord (the normal small canal running through the center of the spinal cord). Some physicians use the terms syringomyelia or hydromyelia interchangeably. Hydromyelia may also be present in infants and young children with or without brain abnormalities, such as Chiari malformation type II that is seen in patients with spina bifida. The fluid-filled cavities in cases of syringomyelia often do not connect to any other fluid-filled areas or spaces and occur more often in adults than children.
| 1,184 |
Syringomyelia
|
nord_1184_1
|
Symptoms of Syringomyelia
|
The specific symptoms and severity of syringomyelia can vary greatly from one person to another. Some individuals may not have any noticeable symptoms (asymptomatic); others may have a variety of symptoms that can progress to cause significant disability. It is important to note the highly variable nature of syringomyelia and to realize that affected individuals can have different sets of symptoms and a different rate of progression (or no progression of the disease at all).Syringomyelia is usually slowly progressive, but rapid onset can occur. Common symptoms include pain in the neck and shoulders. Pain may also affect the arms and hands and may be described as a burning, tingling or piercing sensation. Some affected individuals also experience numbness or decreased sensation, especially to hot and cold. Muscle weakness and wasting, especially of the hands, arms, and eventually the shoulders, may also develop. The upper (cervical and thoracic) portions of the spinal cord are often affected in syringomyelia. Affected individuals may first notice a loss of feeling for pain and temperature in their fingers, hands, arms, and upper chest. In the early stages, a sense of touch is still present. A loss of feeling may spread over the shoulders and back, described as a “cape-like” distribution.Affected individuals may also develop pain and stiffness (spasticity) in the legs and uncoordinated movements (ataxia), eventually affecting the ability to walk. In severe cases, paralysis of the arms or legs can occur. Some affected individuals may develop muscle contractions such as small, involuntary muscle contractions or “twitches” (fasciculations).Skeletal abnormalities can develop including the abnormal side-to-side curvature of the spine (scoliosis). In some children, scoliosis may be the only symptom. Some individuals may develop Charcot joints, in which chronic, progressive degeneration of the joint occurs because of damage to the nerves that supply the joint. Charcot joints are initially seen as swelling and redness of the affected areas. Without treatment, deformity of the affected joints can occur.Some affected individuals develop symptoms associated with damage to the autonomic nervous system, which is the part of the nervous system that controls involuntary functions. Such symptoms include loss of bowel and bladder control, excessive sweating (hyperhidrosis), and fluctuating blood pressure levels. Horner’s syndrome, an uncommon condition that develops because of damage to one of the nerves that supplies the eyes and face, may also occur. Horner’s syndrome usually affects one side of the face and is characterized by a droopy eyelid, narrowing of the opening between the eyelids, decreased pupil size, and decreased sweating on the affected side of the face.Individuals with syringomyelia associated with a Chiari malformation may also have a condition called hydrocephalus, in which there is an abnormal accumulation of cerebrospinal fluid in the brain. In infancy, hydrocephalus can cause a variety of symptoms including an abnormally enlarged head, vomiting, headache, sleepiness, irritability, seizures, and downward deviation of the eyes.
|
Symptoms of Syringomyelia. The specific symptoms and severity of syringomyelia can vary greatly from one person to another. Some individuals may not have any noticeable symptoms (asymptomatic); others may have a variety of symptoms that can progress to cause significant disability. It is important to note the highly variable nature of syringomyelia and to realize that affected individuals can have different sets of symptoms and a different rate of progression (or no progression of the disease at all).Syringomyelia is usually slowly progressive, but rapid onset can occur. Common symptoms include pain in the neck and shoulders. Pain may also affect the arms and hands and may be described as a burning, tingling or piercing sensation. Some affected individuals also experience numbness or decreased sensation, especially to hot and cold. Muscle weakness and wasting, especially of the hands, arms, and eventually the shoulders, may also develop. The upper (cervical and thoracic) portions of the spinal cord are often affected in syringomyelia. Affected individuals may first notice a loss of feeling for pain and temperature in their fingers, hands, arms, and upper chest. In the early stages, a sense of touch is still present. A loss of feeling may spread over the shoulders and back, described as a “cape-like” distribution.Affected individuals may also develop pain and stiffness (spasticity) in the legs and uncoordinated movements (ataxia), eventually affecting the ability to walk. In severe cases, paralysis of the arms or legs can occur. Some affected individuals may develop muscle contractions such as small, involuntary muscle contractions or “twitches” (fasciculations).Skeletal abnormalities can develop including the abnormal side-to-side curvature of the spine (scoliosis). In some children, scoliosis may be the only symptom. Some individuals may develop Charcot joints, in which chronic, progressive degeneration of the joint occurs because of damage to the nerves that supply the joint. Charcot joints are initially seen as swelling and redness of the affected areas. Without treatment, deformity of the affected joints can occur.Some affected individuals develop symptoms associated with damage to the autonomic nervous system, which is the part of the nervous system that controls involuntary functions. Such symptoms include loss of bowel and bladder control, excessive sweating (hyperhidrosis), and fluctuating blood pressure levels. Horner’s syndrome, an uncommon condition that develops because of damage to one of the nerves that supplies the eyes and face, may also occur. Horner’s syndrome usually affects one side of the face and is characterized by a droopy eyelid, narrowing of the opening between the eyelids, decreased pupil size, and decreased sweating on the affected side of the face.Individuals with syringomyelia associated with a Chiari malformation may also have a condition called hydrocephalus, in which there is an abnormal accumulation of cerebrospinal fluid in the brain. In infancy, hydrocephalus can cause a variety of symptoms including an abnormally enlarged head, vomiting, headache, sleepiness, irritability, seizures, and downward deviation of the eyes.
| 1,184 |
Syringomyelia
|
nord_1184_2
|
Causes of Syringomyelia
|
The exact, underlying reason for the formation of a syrinx is unknown. Most theories implicate the obstruction or disruption of the flow of cerebrospinal fluid (CSF) as the most common cause. CSF is a clear fluid that surrounds and is within the brain and surrounds the spinal cord. CSF has several functions including protecting and cushioning the brain and giving the brain buoyancy. CSF is also found in the central canal, a small canal that runs through the center of the spinal cord in infants. The central canal eventually collapses over time.
A variety of conditions that block or impair the normal flow cerebrospinal fluid have been associated with syringomyelia. The condition most commonly associated with syringomyelia is the Chiari malformations, a group of complex brain abnormalities that affect the area in the lower back of the skull where the brain and spinal cord connect (craniovertebral junction).Syringomyelia can also develop following spinal cord injury (SCI). These cases are sometimes referred to as posttraumatic syringomyelia. The development of posttraumatic syringomyelia may occur many years after the initial traumatic injury.Additional conditions that are associated with syringomyelia include certain spinal cord tumors, meningitis, inflammation of the arachnoid membrane (arachnoiditis), one of the membranes that surrounds and protects the spinal cord, and a tethered spinal cord, which is usually a stretch-induced functional disorder associated with the fixation (tethering) effect of inelastic tissue (filum terminale usually infiltrated with fat) found at the caudal end of the spinal cord, limiting its movement.Spinal dysraphism (spina bifida occulta), which is characterized by malformations of the spinal canal and its contents, can also be associated with syringomyelia. Spinal dysraphism is often associated with a tethered spinal cord.In some individuals, syringomyelia can develop without any known cause. These cases are referred to as idiopathic syringomyelia.
|
Causes of Syringomyelia. The exact, underlying reason for the formation of a syrinx is unknown. Most theories implicate the obstruction or disruption of the flow of cerebrospinal fluid (CSF) as the most common cause. CSF is a clear fluid that surrounds and is within the brain and surrounds the spinal cord. CSF has several functions including protecting and cushioning the brain and giving the brain buoyancy. CSF is also found in the central canal, a small canal that runs through the center of the spinal cord in infants. The central canal eventually collapses over time.
A variety of conditions that block or impair the normal flow cerebrospinal fluid have been associated with syringomyelia. The condition most commonly associated with syringomyelia is the Chiari malformations, a group of complex brain abnormalities that affect the area in the lower back of the skull where the brain and spinal cord connect (craniovertebral junction).Syringomyelia can also develop following spinal cord injury (SCI). These cases are sometimes referred to as posttraumatic syringomyelia. The development of posttraumatic syringomyelia may occur many years after the initial traumatic injury.Additional conditions that are associated with syringomyelia include certain spinal cord tumors, meningitis, inflammation of the arachnoid membrane (arachnoiditis), one of the membranes that surrounds and protects the spinal cord, and a tethered spinal cord, which is usually a stretch-induced functional disorder associated with the fixation (tethering) effect of inelastic tissue (filum terminale usually infiltrated with fat) found at the caudal end of the spinal cord, limiting its movement.Spinal dysraphism (spina bifida occulta), which is characterized by malformations of the spinal canal and its contents, can also be associated with syringomyelia. Spinal dysraphism is often associated with a tethered spinal cord.In some individuals, syringomyelia can develop without any known cause. These cases are referred to as idiopathic syringomyelia.
| 1,184 |
Syringomyelia
|
nord_1184_3
|
Affects of Syringomyelia
|
Syringomyelia most commonly presents in young adults between 20 and 40 years of age, but can also develop in young children or older adults. Some reports suggest that syringomyelia is slightly more common in males than females. One estimate places the incidence at 8.4 individuals per 100,000 in the general population in the United States.
|
Affects of Syringomyelia. Syringomyelia most commonly presents in young adults between 20 and 40 years of age, but can also develop in young children or older adults. Some reports suggest that syringomyelia is slightly more common in males than females. One estimate places the incidence at 8.4 individuals per 100,000 in the general population in the United States.
| 1,184 |
Syringomyelia
|
nord_1184_4
|
Related disorders of Syringomyelia
|
Chiari malformations are commonly associated with syringomyelia. They are a group of complex brain abnormalities that affect the area in lower back of the skull where the brain and spinal cord connect. Chiari malformations are thought to be present at birth (congenital), although in many cases, the symptoms that they cause may not become apparent until adulthood. In extremely rare cases, a Chiari malformation may be acquired during life. The exact cause of Chiari malformations is not known, but often the cavity near the base of the skull (posterior cranial fossa) is abnormally small in relation to the size of the cerebellum, which this portion of the skull encloses. Researchers believe that in some cases, the small posterior cranial fossa may cause the developing brain, specifically the cerebellum and the brainstem, to be pushed downward. Part of the cerebellum (known as the cerebellar tonsils) may protrude (herniate) through the foramen magnum, which is the normal opening found in the occipital bone at the base of the skull. The tonsils thus interfere with the flow of cerebrospinal fluid (CSF) from the skull into the spinal canal. A Chiari malformation can also cause hydrocephalus (pressure due to excessive cerebrospinal fluid accumulation in the brain), potentially causing a wide variety of symptoms. The severity of Chiari malformations can vary dramatically as well. Some affected individuals may not develop any symptoms (asymptomatic); in others, severe, potentially debilitating or life-threatening symptoms can develop. Traditionally, Chiari malformations have been defined and classified by how much of the cerebellum and other parts of the posterior cranial fossa protrude through the foramen magnum. A diagnosis of a Chiari type I malformation usually signifies that the cerebellar tonsils protrude below the foramen magnum (often cited as at least 5 millimeters). Researchers have determined that the length of tonsil descent in a Chiari malformation does not always correspond to the severity of symptoms or to the response to treatment. In fact, some individuals are classified as having Chiari malformation type 0. These individuals make up a very small percent of the Chiari population and are defined as having minimal or no descent of the cerebellar tonsils and syringomyelia that improves after surgical treatment at the base of the skull. Chiari type II malformations are seen only in patients with spina bifida. There is also herniation of the cerebellum through the foramen magnum but instead of the cerebellar tonsils, the cerebellar vermis is herniated. Syringomyelia is also very common in patients with the Chiari II malformation. Research is ongoing to understand the complex, underlying mechanisms that cause Chiari malformations. (For more information on this disorder, choose “Chiari” as your search term in the Rare Disease Database.)There are numerous conditions that can cause neurological symptoms similar to those seen in individuals with syringomyelia including amyotrophic lateral sclerosis, central pontine myelinolysis, multiple sclerosis, spinal muscular atrophy, diabetic neuropathy, chronic inflammatory demyelinating polyneuropathy, arteriovenous malformations, and ankylosing spondylitis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Syringobulbia is a neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord that extends to involve the lower brainstem (medulla). It usually occurs as a slit-like gap within the lower brainstem that may affect one or more of the cranial nerves. Sensory and motor nerve pathways may be affected by syringobulbia. This disorder is usually associated with syringomyelia, in which the syrinx is limited to the spinal cord, and to the Chiari I malformation. (For more information on this disorder, choose “syringobulbia” as your search term in the Rare Disease Database.)
|
Related disorders of Syringomyelia. Chiari malformations are commonly associated with syringomyelia. They are a group of complex brain abnormalities that affect the area in lower back of the skull where the brain and spinal cord connect. Chiari malformations are thought to be present at birth (congenital), although in many cases, the symptoms that they cause may not become apparent until adulthood. In extremely rare cases, a Chiari malformation may be acquired during life. The exact cause of Chiari malformations is not known, but often the cavity near the base of the skull (posterior cranial fossa) is abnormally small in relation to the size of the cerebellum, which this portion of the skull encloses. Researchers believe that in some cases, the small posterior cranial fossa may cause the developing brain, specifically the cerebellum and the brainstem, to be pushed downward. Part of the cerebellum (known as the cerebellar tonsils) may protrude (herniate) through the foramen magnum, which is the normal opening found in the occipital bone at the base of the skull. The tonsils thus interfere with the flow of cerebrospinal fluid (CSF) from the skull into the spinal canal. A Chiari malformation can also cause hydrocephalus (pressure due to excessive cerebrospinal fluid accumulation in the brain), potentially causing a wide variety of symptoms. The severity of Chiari malformations can vary dramatically as well. Some affected individuals may not develop any symptoms (asymptomatic); in others, severe, potentially debilitating or life-threatening symptoms can develop. Traditionally, Chiari malformations have been defined and classified by how much of the cerebellum and other parts of the posterior cranial fossa protrude through the foramen magnum. A diagnosis of a Chiari type I malformation usually signifies that the cerebellar tonsils protrude below the foramen magnum (often cited as at least 5 millimeters). Researchers have determined that the length of tonsil descent in a Chiari malformation does not always correspond to the severity of symptoms or to the response to treatment. In fact, some individuals are classified as having Chiari malformation type 0. These individuals make up a very small percent of the Chiari population and are defined as having minimal or no descent of the cerebellar tonsils and syringomyelia that improves after surgical treatment at the base of the skull. Chiari type II malformations are seen only in patients with spina bifida. There is also herniation of the cerebellum through the foramen magnum but instead of the cerebellar tonsils, the cerebellar vermis is herniated. Syringomyelia is also very common in patients with the Chiari II malformation. Research is ongoing to understand the complex, underlying mechanisms that cause Chiari malformations. (For more information on this disorder, choose “Chiari” as your search term in the Rare Disease Database.)There are numerous conditions that can cause neurological symptoms similar to those seen in individuals with syringomyelia including amyotrophic lateral sclerosis, central pontine myelinolysis, multiple sclerosis, spinal muscular atrophy, diabetic neuropathy, chronic inflammatory demyelinating polyneuropathy, arteriovenous malformations, and ankylosing spondylitis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Syringobulbia is a neurological disorder characterized by a fluid-filled cavity (syrinx) within the spinal cord that extends to involve the lower brainstem (medulla). It usually occurs as a slit-like gap within the lower brainstem that may affect one or more of the cranial nerves. Sensory and motor nerve pathways may be affected by syringobulbia. This disorder is usually associated with syringomyelia, in which the syrinx is limited to the spinal cord, and to the Chiari I malformation. (For more information on this disorder, choose “syringobulbia” as your search term in the Rare Disease Database.)
| 1,184 |
Syringomyelia
|
nord_1184_5
|
Diagnosis of Syringomyelia
|
A diagnosis of syringomyelia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. In some cases, syringomyelia is discovered incidentally when a person is being evaluated for another reason.Clinical Testing and Workup
A specialized imaging technique called magnetic resonance imaging (MRI) is used to diagnose syringomyelia. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues such as the brain and spinal cord. An MRI can reveal a syrinx or another condition related to syringomyelia such as an intraspinal tumor or Chiari malformation. The location and extent of the syrinx is much more accurately determined and treatment can begin, when appropriate, earlier than in the past with older diagnostic techniques (e.g., myelogram).
|
Diagnosis of Syringomyelia. A diagnosis of syringomyelia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. In some cases, syringomyelia is discovered incidentally when a person is being evaluated for another reason.Clinical Testing and Workup
A specialized imaging technique called magnetic resonance imaging (MRI) is used to diagnose syringomyelia. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues such as the brain and spinal cord. An MRI can reveal a syrinx or another condition related to syringomyelia such as an intraspinal tumor or Chiari malformation. The location and extent of the syrinx is much more accurately determined and treatment can begin, when appropriate, earlier than in the past with older diagnostic techniques (e.g., myelogram).
| 1,184 |
Syringomyelia
|
nord_1184_6
|
Therapies of Syringomyelia
|
Treatment
The treatment of syringomyelia is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, neurosurgeons, surgeons, eye specialists (ophthalmologists) and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease progression; the presence or absence of certain symptoms; the underlying cause; the impact of symptoms on quality of life; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Some individuals with syringomyelia who do not have any symptoms may not require treatment, but should be regularly monitored to see whether the disorder progresses.General therapeutic options include pain medications (analgesics), physical therapy, and a reduction in activities, especially those that require straining such as heavy lifting. The goal of treatment for syringomyelia is to restore the proper flow of cerebrospinal fluid and to remove the pressure that a syrinx places on the spinal cord. Initial treatment is usually targeted at the underlying cause of syringomyelia.
There is no specific, agreed-upon therapy or treatment regimen for the most common cause of a syrinx, a Chiari malformation. Neurosurgeons and other physicians may disagree as to the best approach to treat a Chiari malformation. Different neurosurgeons may recommend different surgical techniques or treatment regimens.Like syringomyelia, individuals with a Chiari malformation who do not have symptoms are generally not treated, but monitored to see whether the disorder progresses. If mild or nonspecific symptoms are present, such as neck pain or headaches, physicians may recommend conservative treatment. Symptomatic Chiari malformations are most often treated by surgery. There are no specific criteria or objective tests that can be used to determine when to undergo surgery or the best procedures to choose. The most common surgery is known as posterior fossa decompression. With this procedure, a surgeon creates room by removing small pieces of bone in the back of the skull, thereby enlarging the foramen magnum. This relieves pressure and reduces compression of the brainstem. The surgeon may also choose to open the covering (dura mater) of the brain in this region and explore the herniated tissue and then sew in a graft (duraplasty).If hydrocephalus is associated with the Chiari malformation-related syrinx, then the surgeon will usually treat this first. The most common surgical treatment is to place a shunt that connects the dilated ventricles of the brain to another cavity of the body. The most common cavity chosen is the abdomen. Once the hydrocephalus is treated, then the Chiari malformation is addressed.Surgery may be used to treat other conditions that cause syringomyelia including surgery to remove a tumor. Tethered spinal cord may require surgery to release the tension of the cord.In some cases, a tiny tube called a shunt/stent may be placed into the syrinx. The shunt allows the fluid within the syrinx to drain to an area outside of the spinal column. Shunting can stop the progression of the disorder and relieve some symptoms such as pain and headaches. However, shunts can be associated with significant side effects including spinal cord injury or infection, bleeding (hemorrhaging), and blockage.Posttraumatic syringomyelia may be difficult to treat. Surgery is recommended for individuals with neurological deterioration and/or intractable pain. Surgery is aimed at expanding the area around the spinal cord by the site of trauma or injury and to decrease fluid volume. The insertion of shunt may also be used to treat posttraumatic syringomyelia. Shunting in posttraumatic syringomyelia carries risks including further spinal cord injury and may need to be replaced if the shunt becomes clogged or defective. Many physicians consider shunts a last resort for individuals with posttraumatic syringomyelia.Surgery for syringomyelia can often lead to an improvement of symptoms and stabilization of the disorder in many individuals. However, syringomyelia can recur after successful treatment, thereby necessitating more operations.
After surgery, the physician will evaluate the syrinx to make sure that it stabilizes or decreases in size. These evaluations will entail obtaining an MRI.
|
Therapies of Syringomyelia. Treatment
The treatment of syringomyelia is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, neurosurgeons, surgeons, eye specialists (ophthalmologists) and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease progression; the presence or absence of certain symptoms; the underlying cause; the impact of symptoms on quality of life; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Some individuals with syringomyelia who do not have any symptoms may not require treatment, but should be regularly monitored to see whether the disorder progresses.General therapeutic options include pain medications (analgesics), physical therapy, and a reduction in activities, especially those that require straining such as heavy lifting. The goal of treatment for syringomyelia is to restore the proper flow of cerebrospinal fluid and to remove the pressure that a syrinx places on the spinal cord. Initial treatment is usually targeted at the underlying cause of syringomyelia.
There is no specific, agreed-upon therapy or treatment regimen for the most common cause of a syrinx, a Chiari malformation. Neurosurgeons and other physicians may disagree as to the best approach to treat a Chiari malformation. Different neurosurgeons may recommend different surgical techniques or treatment regimens.Like syringomyelia, individuals with a Chiari malformation who do not have symptoms are generally not treated, but monitored to see whether the disorder progresses. If mild or nonspecific symptoms are present, such as neck pain or headaches, physicians may recommend conservative treatment. Symptomatic Chiari malformations are most often treated by surgery. There are no specific criteria or objective tests that can be used to determine when to undergo surgery or the best procedures to choose. The most common surgery is known as posterior fossa decompression. With this procedure, a surgeon creates room by removing small pieces of bone in the back of the skull, thereby enlarging the foramen magnum. This relieves pressure and reduces compression of the brainstem. The surgeon may also choose to open the covering (dura mater) of the brain in this region and explore the herniated tissue and then sew in a graft (duraplasty).If hydrocephalus is associated with the Chiari malformation-related syrinx, then the surgeon will usually treat this first. The most common surgical treatment is to place a shunt that connects the dilated ventricles of the brain to another cavity of the body. The most common cavity chosen is the abdomen. Once the hydrocephalus is treated, then the Chiari malformation is addressed.Surgery may be used to treat other conditions that cause syringomyelia including surgery to remove a tumor. Tethered spinal cord may require surgery to release the tension of the cord.In some cases, a tiny tube called a shunt/stent may be placed into the syrinx. The shunt allows the fluid within the syrinx to drain to an area outside of the spinal column. Shunting can stop the progression of the disorder and relieve some symptoms such as pain and headaches. However, shunts can be associated with significant side effects including spinal cord injury or infection, bleeding (hemorrhaging), and blockage.Posttraumatic syringomyelia may be difficult to treat. Surgery is recommended for individuals with neurological deterioration and/or intractable pain. Surgery is aimed at expanding the area around the spinal cord by the site of trauma or injury and to decrease fluid volume. The insertion of shunt may also be used to treat posttraumatic syringomyelia. Shunting in posttraumatic syringomyelia carries risks including further spinal cord injury and may need to be replaced if the shunt becomes clogged or defective. Many physicians consider shunts a last resort for individuals with posttraumatic syringomyelia.Surgery for syringomyelia can often lead to an improvement of symptoms and stabilization of the disorder in many individuals. However, syringomyelia can recur after successful treatment, thereby necessitating more operations.
After surgery, the physician will evaluate the syrinx to make sure that it stabilizes or decreases in size. These evaluations will entail obtaining an MRI.
| 1,184 |
Syringomyelia
|
nord_1185_0
|
Overview of Systemic Capillary Leak Syndrome
|
IntroductionSystemic capillary leak syndrome (SCLS) is a rare disorder characterized by acute and severe recurrent attacks associated with a rapid fall in blood pressure as a result of fluid leaks from smaller vessels called capillaries. Attacks often last several days and require emergency care. They are sometimes life threatening. SCLS occurs most often in adults and the disease is very rare in children.
|
Overview of Systemic Capillary Leak Syndrome. IntroductionSystemic capillary leak syndrome (SCLS) is a rare disorder characterized by acute and severe recurrent attacks associated with a rapid fall in blood pressure as a result of fluid leaks from smaller vessels called capillaries. Attacks often last several days and require emergency care. They are sometimes life threatening. SCLS occurs most often in adults and the disease is very rare in children.
| 1,185 |
Systemic Capillary Leak Syndrome
|
nord_1185_1
|
Symptoms of Systemic Capillary Leak Syndrome
|
Symptoms of SCLS usually involve a brief warning, which can include nasal congestion and cough that might be associated with a viral upper respiratory infection. Patients may develop malaise, nausea, lightheadedness, a faint feeling, abdominal pain, headache and swelling of extremities. Fever, chills, rash, or signs of infection may be absent. Patients may also exhibit elevated white blood cell count (leukocytosis) which may produce a false diagnosis when blood is tested. Spontaneous resolution of symptoms is uncommon without treatment.A chronic form of SCLS has been reported that is manifested by swelling of the extremities and fluid accumulation around the heart and lungs. The characteristic increase in hemoglobin and blood cell count (hematocrit) may be absent in such cases, but serum albumin is characteristically decreased due to loss of fluid in the tissues. Low blood volume with a decrease in blood pressure are uncommon in the chronic form. These patients may respond to glucocorticoids, diuretics, and aminophylline, or IVIG.
|
Symptoms of Systemic Capillary Leak Syndrome. Symptoms of SCLS usually involve a brief warning, which can include nasal congestion and cough that might be associated with a viral upper respiratory infection. Patients may develop malaise, nausea, lightheadedness, a faint feeling, abdominal pain, headache and swelling of extremities. Fever, chills, rash, or signs of infection may be absent. Patients may also exhibit elevated white blood cell count (leukocytosis) which may produce a false diagnosis when blood is tested. Spontaneous resolution of symptoms is uncommon without treatment.A chronic form of SCLS has been reported that is manifested by swelling of the extremities and fluid accumulation around the heart and lungs. The characteristic increase in hemoglobin and blood cell count (hematocrit) may be absent in such cases, but serum albumin is characteristically decreased due to loss of fluid in the tissues. Low blood volume with a decrease in blood pressure are uncommon in the chronic form. These patients may respond to glucocorticoids, diuretics, and aminophylline, or IVIG.
| 1,185 |
Systemic Capillary Leak Syndrome
|
nord_1185_2
|
Causes of Systemic Capillary Leak Syndrome
|
The cause of SCLS is not yet known, but there appears to be no hereditary predisposition for the condition. More than half of patients have a monoclonal or M protein detected in the blood. The level of M protein is usually low. The M protein is produced by plasma cells in the marrow. The role of the M protein in acute attacks is unknown. Many possible explanations for the production of M protein in SCLS patients have been suggested including an autoimmune mechanism in which the immune system mistakenly attacks the body. Recently it has been suggested that capillary lining cells may be damaged by a factor in the blood which is produced during the acute attack.
|
Causes of Systemic Capillary Leak Syndrome. The cause of SCLS is not yet known, but there appears to be no hereditary predisposition for the condition. More than half of patients have a monoclonal or M protein detected in the blood. The level of M protein is usually low. The M protein is produced by plasma cells in the marrow. The role of the M protein in acute attacks is unknown. Many possible explanations for the production of M protein in SCLS patients have been suggested including an autoimmune mechanism in which the immune system mistakenly attacks the body. Recently it has been suggested that capillary lining cells may be damaged by a factor in the blood which is produced during the acute attack.
| 1,185 |
Systemic Capillary Leak Syndrome
|
nord_1185_3
|
Affects of Systemic Capillary Leak Syndrome
|
There are less than 500 patients with SCLS reported in the world literature since its first description in 1960 by Clarkson. Although most clinical studies were performed in Caucasians, SCLS has been recognized in a range of racial backgrounds and nationalities. SCLS seems to occur slightly more often in older male adults, but females have also been affected. Most diagnoses are made at the median age of 48 years of age. The disease may be more frequent than the literature suggests because the diagnosis is often missed or delayed.
|
Affects of Systemic Capillary Leak Syndrome. There are less than 500 patients with SCLS reported in the world literature since its first description in 1960 by Clarkson. Although most clinical studies were performed in Caucasians, SCLS has been recognized in a range of racial backgrounds and nationalities. SCLS seems to occur slightly more often in older male adults, but females have also been affected. Most diagnoses are made at the median age of 48 years of age. The disease may be more frequent than the literature suggests because the diagnosis is often missed or delayed.
| 1,185 |
Systemic Capillary Leak Syndrome
|
nord_1185_4
|
Related disorders of Systemic Capillary Leak Syndrome
|
Symptoms of the following disorders may be similar to those of systemic capillary leak syndrome. Comparisons may be useful for a differential diagnosis:SCLS may be mistaken for a severe infection such as septic shock or toxic shock syndrome. Some features such as the swelling may lead to a suspected diagnosis of heart failure or kidney disease. C-1 esterase inhibitor deficiency syndrome may present with a type of recurring edema called angioedema and is often thought of in patients presenting with SCLS. In some patients, the hemoconcentration and resulting high hematocrit and hemoglobin level have been mistaken for polycythemia.
|
Related disorders of Systemic Capillary Leak Syndrome. Symptoms of the following disorders may be similar to those of systemic capillary leak syndrome. Comparisons may be useful for a differential diagnosis:SCLS may be mistaken for a severe infection such as septic shock or toxic shock syndrome. Some features such as the swelling may lead to a suspected diagnosis of heart failure or kidney disease. C-1 esterase inhibitor deficiency syndrome may present with a type of recurring edema called angioedema and is often thought of in patients presenting with SCLS. In some patients, the hemoconcentration and resulting high hematocrit and hemoglobin level have been mistaken for polycythemia.
| 1,185 |
Systemic Capillary Leak Syndrome
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.