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nord_228_4 | Related disorders of Chikungunya | Symptoms of the following disorders can be similar to those of Chikungunya. Comparisons may be useful for a differential diagnosis:O'Nyong-Nyong Virus is an infectious disease that first appeared in Africa in the late 1950's. The symptoms are similar to those of Chikungunya and include fever, joint pain, and skin rashes. People with O'Nyong-Nyong Virus usually have swollen lymph nodes. Typically the fever is short in duration and the joint pain is mild.Mayaro Virus is an infectious disease that first appeared in South America (Brazil and Bolivia). It is characterized by fever, chills, severe headache, muscle pain, and dizziness. Pain and swelling occur in the small joints, wrists, fingers, ankles, and/or toes. The symptoms are similar to those of Chikungunya.Ross River Virus is an infectious disease characterized by fever, swollen painful joints, and skin rashes. It first occurred in Australia in 1928. Symptoms include headache, muscle pain, nausea, and vomiting. Some people may experience tenderness on the palms of the hands and soles of the feet. The knees are commonly swollen and painful. A skin rash typically begins on the cheeks and forehead and spreads to the trunk, arms, and legs. | Related disorders of Chikungunya. Symptoms of the following disorders can be similar to those of Chikungunya. Comparisons may be useful for a differential diagnosis:O'Nyong-Nyong Virus is an infectious disease that first appeared in Africa in the late 1950's. The symptoms are similar to those of Chikungunya and include fever, joint pain, and skin rashes. People with O'Nyong-Nyong Virus usually have swollen lymph nodes. Typically the fever is short in duration and the joint pain is mild.Mayaro Virus is an infectious disease that first appeared in South America (Brazil and Bolivia). It is characterized by fever, chills, severe headache, muscle pain, and dizziness. Pain and swelling occur in the small joints, wrists, fingers, ankles, and/or toes. The symptoms are similar to those of Chikungunya.Ross River Virus is an infectious disease characterized by fever, swollen painful joints, and skin rashes. It first occurred in Australia in 1928. Symptoms include headache, muscle pain, nausea, and vomiting. Some people may experience tenderness on the palms of the hands and soles of the feet. The knees are commonly swollen and painful. A skin rash typically begins on the cheeks and forehead and spreads to the trunk, arms, and legs. | 228 | Chikungunya |
nord_228_5 | Diagnosis of Chikungunya | Diagnosis of Chikungunya. | 228 | Chikungunya |
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nord_228_6 | Therapies of Chikungunya | The diagnosis of Chikungunya may be confirmed by a specialized blood test that detects immune responses to the virus (ELISA test). The symptoms of Chikungunya improve spontaneously after several weeks. There is no specific treatment. However, bed rest and antiinflammatory medications (i.e., ibuprofen) may be useful. As with other viral diseases, antibiotics are not effective in treating this disease. | Therapies of Chikungunya. The diagnosis of Chikungunya may be confirmed by a specialized blood test that detects immune responses to the virus (ELISA test). The symptoms of Chikungunya improve spontaneously after several weeks. There is no specific treatment. However, bed rest and antiinflammatory medications (i.e., ibuprofen) may be useful. As with other viral diseases, antibiotics are not effective in treating this disease. | 228 | Chikungunya |
nord_229_0 | Overview of Chilaiditi’s Syndrome | Chilaiditi's syndrome is a rare condition in which a portion of the colon is abnormally located (interposed) in between the liver and the diaphragm. The diaphragm is the muscle that separates the chest cavity from the abdomen. Chilaiditi's syndrome can cause a variety of symptoms including abdominal pain, nausea, vomiting, and small bowel obstruction. The specific symptoms and presentation of Chilaiditi's syndrome can vary greatly from one person to another. The cause of Chilaiditi's syndrome is not fully understood.In most cases, interposition of a portion of colon between the liver and diaphragm does not cause symptoms (asymptomatic) and is often an incidental finding in the elderly. When no symptoms are present, this clinical finding is referred to as Chilaiditi's sign. In rare cases, symptoms do develop; these cases are referred to as Chilaiditi's syndrome. | Overview of Chilaiditi’s Syndrome. Chilaiditi's syndrome is a rare condition in which a portion of the colon is abnormally located (interposed) in between the liver and the diaphragm. The diaphragm is the muscle that separates the chest cavity from the abdomen. Chilaiditi's syndrome can cause a variety of symptoms including abdominal pain, nausea, vomiting, and small bowel obstruction. The specific symptoms and presentation of Chilaiditi's syndrome can vary greatly from one person to another. The cause of Chilaiditi's syndrome is not fully understood.In most cases, interposition of a portion of colon between the liver and diaphragm does not cause symptoms (asymptomatic) and is often an incidental finding in the elderly. When no symptoms are present, this clinical finding is referred to as Chilaiditi's sign. In rare cases, symptoms do develop; these cases are referred to as Chilaiditi's syndrome. | 229 | Chilaiditi’s Syndrome |
nord_229_1 | Symptoms of Chilaiditi’s Syndrome | The symptoms of Chilaiditi's syndrome may vary from one person to another. The presentation and specific symptoms that develop can be significantly different. Chronic, recurrent episodes of abdominal pain are a common finding. Abdominal pain may be mild and come and go (intermittent). However, abdominal pain can be severe and force affected individuals to go to the emergency room. Additional symptoms can occur with Chilaiditi's syndrome. These symptoms can occur together in a wide variety of different combinations. Affected individuals will not have all of these symptoms and some affected individuals will not have any of these symptoms. Additional symptoms that have been reported in Chilaiditi's syndrome include nausea, vomiting, constipation, indigestion (dyspepsia), abnormal twisting of the intestines (volvulus) causing obstruction, abdominal swelling (distention), difficulty swallowing (dysphagia), and tenderness in the upper, central area of the abdomen (epigastric region). In some cases, Chilaiditi's syndrome has been associated with breathing problems (respiratory distress). | Symptoms of Chilaiditi’s Syndrome. The symptoms of Chilaiditi's syndrome may vary from one person to another. The presentation and specific symptoms that develop can be significantly different. Chronic, recurrent episodes of abdominal pain are a common finding. Abdominal pain may be mild and come and go (intermittent). However, abdominal pain can be severe and force affected individuals to go to the emergency room. Additional symptoms can occur with Chilaiditi's syndrome. These symptoms can occur together in a wide variety of different combinations. Affected individuals will not have all of these symptoms and some affected individuals will not have any of these symptoms. Additional symptoms that have been reported in Chilaiditi's syndrome include nausea, vomiting, constipation, indigestion (dyspepsia), abnormal twisting of the intestines (volvulus) causing obstruction, abdominal swelling (distention), difficulty swallowing (dysphagia), and tenderness in the upper, central area of the abdomen (epigastric region). In some cases, Chilaiditi's syndrome has been associated with breathing problems (respiratory distress). | 229 | Chilaiditi’s Syndrome |
nord_229_2 | Causes of Chilaiditi’s Syndrome | The exact cause of Chilaiditi's syndrome is unknown. The condition occurs with greater frequency in individuals with chronic lung disease, scarring of the liver (cirrhosis), and the accumulation of fluid within the abdominal cavity (ascites). Ascites can be associated with a wide variety of medical conditions. Additional predisposing factors include abnormal elongation of the colon or abnormal looseness (laxity) of certain ligaments of the colon and liver. Ligaments are tough, fibrous bands of tissue that primarily serve to connect or support structures within the body. According to the medical literature, other factors may play a role in the development of Chilaiditi's syndrome in some cases including reduced liver volume, paralysis of the motor nerve of the diaphragm (phrenic nerve palsy) and obesity. | Causes of Chilaiditi’s Syndrome. The exact cause of Chilaiditi's syndrome is unknown. The condition occurs with greater frequency in individuals with chronic lung disease, scarring of the liver (cirrhosis), and the accumulation of fluid within the abdominal cavity (ascites). Ascites can be associated with a wide variety of medical conditions. Additional predisposing factors include abnormal elongation of the colon or abnormal looseness (laxity) of certain ligaments of the colon and liver. Ligaments are tough, fibrous bands of tissue that primarily serve to connect or support structures within the body. According to the medical literature, other factors may play a role in the development of Chilaiditi's syndrome in some cases including reduced liver volume, paralysis of the motor nerve of the diaphragm (phrenic nerve palsy) and obesity. | 229 | Chilaiditi’s Syndrome |
nord_229_3 | Affects of Chilaiditi’s Syndrome | Chilaiditi's syndrome affects males and females in equal numbers. It is more common in older adults, but can occur at any age and has been reported in children. The incidence of Chilaiditi's syndrome is unknown. One published report estimated the incidence at .025-.28 percent of the general population. Chilaiditi's syndrome was first described in the medical literature in 1910 by a Greek radiologist named Demetrius Chilaiditi. | Affects of Chilaiditi’s Syndrome. Chilaiditi's syndrome affects males and females in equal numbers. It is more common in older adults, but can occur at any age and has been reported in children. The incidence of Chilaiditi's syndrome is unknown. One published report estimated the incidence at .025-.28 percent of the general population. Chilaiditi's syndrome was first described in the medical literature in 1910 by a Greek radiologist named Demetrius Chilaiditi. | 229 | Chilaiditi’s Syndrome |
nord_229_4 | Related disorders of Chilaiditi’s Syndrome | Symptoms of the following disorders can be similar to those of Chilaiditi's syndrome. Comparisons may be useful for a differential diagnosis. Pneumoperitoneum is the abnormal presence of gas or air within the abdominal cavity. Pneumoperitoneum can have a variety of different causes. The specific symptoms that occur depend upon the cause. Chilaiditi's syndrome can potentially be mistaken for pneunoperitoneum, which can result in unnecessary surgery. | Related disorders of Chilaiditi’s Syndrome. Symptoms of the following disorders can be similar to those of Chilaiditi's syndrome. Comparisons may be useful for a differential diagnosis. Pneumoperitoneum is the abnormal presence of gas or air within the abdominal cavity. Pneumoperitoneum can have a variety of different causes. The specific symptoms that occur depend upon the cause. Chilaiditi's syndrome can potentially be mistaken for pneunoperitoneum, which can result in unnecessary surgery. | 229 | Chilaiditi’s Syndrome |
nord_229_5 | Diagnosis of Chilaiditi’s Syndrome | A diagnosis of Chilaiditi's syndrome is made based upon imaging (radiographic) confirmation of the abnormal positioning of the colon and the occurrence of associated symptoms. Such imaging techniques may include chest and abdominal x- rays, ultrasounds, or computerized tomography (CT) scanning. | Diagnosis of Chilaiditi’s Syndrome. A diagnosis of Chilaiditi's syndrome is made based upon imaging (radiographic) confirmation of the abnormal positioning of the colon and the occurrence of associated symptoms. Such imaging techniques may include chest and abdominal x- rays, ultrasounds, or computerized tomography (CT) scanning. | 229 | Chilaiditi’s Syndrome |
nord_229_6 | Therapies of Chilaiditi’s Syndrome | TreatmentThe treatment of Chilaiditi's syndrome is directed toward the specific symptoms that are apparent in each individual. Some affected individuals may not require any therapy. The removal of pressure from the intestines (bowl decompression) has alleviated symptoms in some cases.In some cases, surgical intervention may be required. Surgical techniques that have been used to treat individuals with Chilaiditi's syndrome include the removal of a portion of the colon (transverse colectomy or right hemicolectomy) or the anchoring of a displaced liver to the abdominal wall (hepatopexy). | Therapies of Chilaiditi’s Syndrome. TreatmentThe treatment of Chilaiditi's syndrome is directed toward the specific symptoms that are apparent in each individual. Some affected individuals may not require any therapy. The removal of pressure from the intestines (bowl decompression) has alleviated symptoms in some cases.In some cases, surgical intervention may be required. Surgical techniques that have been used to treat individuals with Chilaiditi's syndrome include the removal of a portion of the colon (transverse colectomy or right hemicolectomy) or the anchoring of a displaced liver to the abdominal wall (hepatopexy). | 229 | Chilaiditi’s Syndrome |
nord_230_0 | Overview of Cholangiocarcinoma | Cholangiocarcinomas are cancers that arise from the cells lining the bile duct. They originally were grouped according to the location from which they arise as intrahepatic (arising from the bile ducts inside the liver) perihilar (arising from the bile ducts where they exit the liver) or distal (arising from the bile ducts outside the liver). Gallbladder cancers are also biliary tract cancers, but arise from the cells lining the inside of the gallbladder. A new way of grouping depends on genetic testing using next generation sequencing that offers several new applicable therapies. More than 95% of tumors arising from the biliary tract are a type of cancer called adenocarcinoma [1]. The majority of patients with bile duct cancers are diagnosed when the cancer is far too advanced to be removed by surgery. In some patients, even if the cancer cannot be removed by surgery, an operation may be needed to relieve jaundice or blockage of the stomach outlet [2]. In patients in whom the cancer is diagnosed at an early stage where surgery is possible, complex operating techniques are often required and surgery should be performed by a specialist surgeon with expertise and experience in dealing with patients with bile duct cancers [3]. | Overview of Cholangiocarcinoma. Cholangiocarcinomas are cancers that arise from the cells lining the bile duct. They originally were grouped according to the location from which they arise as intrahepatic (arising from the bile ducts inside the liver) perihilar (arising from the bile ducts where they exit the liver) or distal (arising from the bile ducts outside the liver). Gallbladder cancers are also biliary tract cancers, but arise from the cells lining the inside of the gallbladder. A new way of grouping depends on genetic testing using next generation sequencing that offers several new applicable therapies. More than 95% of tumors arising from the biliary tract are a type of cancer called adenocarcinoma [1]. The majority of patients with bile duct cancers are diagnosed when the cancer is far too advanced to be removed by surgery. In some patients, even if the cancer cannot be removed by surgery, an operation may be needed to relieve jaundice or blockage of the stomach outlet [2]. In patients in whom the cancer is diagnosed at an early stage where surgery is possible, complex operating techniques are often required and surgery should be performed by a specialist surgeon with expertise and experience in dealing with patients with bile duct cancers [3]. | 230 | Cholangiocarcinoma |
nord_230_1 | Symptoms of Cholangiocarcinoma | Patients may have no symptoms, particularly when the cancer is at an early stage. Occasionally biliary tract cancers are diagnosed incidentally when a CT or MRI scan is done for another reason, or when the gallbladder is removed due to symptomatic gallstones. Patients may have non-specific symptoms including weight loss, abdominal pain, fevers, night sweats and fatigue. Distal and perihilar cholangiocarcinomas or gallbladder cancers more frequently cause patients to develop jaundice due to tumor or lymph nodes blocking a major bile duct [4]. | Symptoms of Cholangiocarcinoma. Patients may have no symptoms, particularly when the cancer is at an early stage. Occasionally biliary tract cancers are diagnosed incidentally when a CT or MRI scan is done for another reason, or when the gallbladder is removed due to symptomatic gallstones. Patients may have non-specific symptoms including weight loss, abdominal pain, fevers, night sweats and fatigue. Distal and perihilar cholangiocarcinomas or gallbladder cancers more frequently cause patients to develop jaundice due to tumor or lymph nodes blocking a major bile duct [4]. | 230 | Cholangiocarcinoma |
nord_230_2 | Causes of Cholangiocarcinoma | Most cases of biliary tract cancer are sporadic, with no identifiable predisposing patient factors. There are several known risk factors for development of cholangiocarcinoma however, including liver cirrhosis, hepatitis B and C, biliary tract stones, liver fluke infections, a congenital anatomical abnormality called a choledochal cyst and the chronic condition of inflamed bile ducts also called primary sclerosing cholangitis. Exposure to some industrial chemicals such as nitrosamines, dioxin, asbestos, and polychlorinated biphenyls are also thought to increase an individual’s risk of developing cholangiocarcinoma. In the USA, gallbladder cancer is commonly associated with the presence of long standing gallstones resulting in calcification of the gallbladder wall or “porcelain gallbladder”. Gallbladder polyps are also associated with increased risk of gallbladder cancer. The incidence of bile duct cancers differs worldwide, likely reflecting both differing genetic predisposition and variable exposure to known risk factors [5]. | Causes of Cholangiocarcinoma. Most cases of biliary tract cancer are sporadic, with no identifiable predisposing patient factors. There are several known risk factors for development of cholangiocarcinoma however, including liver cirrhosis, hepatitis B and C, biliary tract stones, liver fluke infections, a congenital anatomical abnormality called a choledochal cyst and the chronic condition of inflamed bile ducts also called primary sclerosing cholangitis. Exposure to some industrial chemicals such as nitrosamines, dioxin, asbestos, and polychlorinated biphenyls are also thought to increase an individual’s risk of developing cholangiocarcinoma. In the USA, gallbladder cancer is commonly associated with the presence of long standing gallstones resulting in calcification of the gallbladder wall or “porcelain gallbladder”. Gallbladder polyps are also associated with increased risk of gallbladder cancer. The incidence of bile duct cancers differs worldwide, likely reflecting both differing genetic predisposition and variable exposure to known risk factors [5]. | 230 | Cholangiocarcinoma |
nord_230_3 | Affects of Cholangiocarcinoma | Approximately 12,000 new affected individuals of bile duct cancers are diagnosed in the USA each year, of which over 9,000 are gallbladder cancers and distal/perihilar cholangiocarcinomas and 3,000 are intrahepatic cholangiocarcinomas [6]. The overall incidence of perihilar cholangiocarcinoma in the United States is 1 person per 100,000 per year. The incidence of intrahepatic cholangiocarcinoma in the United States is approximately 0.7 per 100,000. During the last 30 years, it appears that the incidence of biliary tract cancers in the United States is increasing [7]. This increase may be due in part to increased recognition of the diagnosis of biliary cancer, cases which may previously have been classified as cancer of unknown origin. Gallbladder cancer is more common in women than in men, and in some countries the rates are three times higher for women. Certain geographic areas are characterized by a high incidence of gallbladder cancer, including Chile, Bolivia and India. A high incidence also has been documented in North American Native Americans and Mexican Americans [7]. | Affects of Cholangiocarcinoma. Approximately 12,000 new affected individuals of bile duct cancers are diagnosed in the USA each year, of which over 9,000 are gallbladder cancers and distal/perihilar cholangiocarcinomas and 3,000 are intrahepatic cholangiocarcinomas [6]. The overall incidence of perihilar cholangiocarcinoma in the United States is 1 person per 100,000 per year. The incidence of intrahepatic cholangiocarcinoma in the United States is approximately 0.7 per 100,000. During the last 30 years, it appears that the incidence of biliary tract cancers in the United States is increasing [7]. This increase may be due in part to increased recognition of the diagnosis of biliary cancer, cases which may previously have been classified as cancer of unknown origin. Gallbladder cancer is more common in women than in men, and in some countries the rates are three times higher for women. Certain geographic areas are characterized by a high incidence of gallbladder cancer, including Chile, Bolivia and India. A high incidence also has been documented in North American Native Americans and Mexican Americans [7]. | 230 | Cholangiocarcinoma |
nord_230_4 | Related disorders of Cholangiocarcinoma | Symptoms of the following disorders can be similar to those of cholangiocarcinoma. Comparisons may be useful for a differential diagnosis.Pancreatic cancer can cause similar symptoms to distal cholangiocarcinoma, and it can be difficult to establish whether a cancer is arising from the bile duct or the pancreas in some cases. Cancers arising from the portion of the bile duct located at or near the pancreas are frequently treated in the same way as pancreatic cancers.Hepatocellular cancer is a more common form of primary liver cancer that arises from the liver cells rather than from the bile ducts. It frequently occurs in patients who have chronic liver damage, and is treated differently to cholangiocarcinoma and gallbladder cancer. The appearance on CT and MRI scans of hepatocellular cancer is different to that of biliary tract cancers, and it is usually possible to distinguish between these diagnoses based on imaging studies. In up to 15% of the cases, primary liver tumors may contain features of both hepatocellular cancers and cholangiocarcinomas; these cancers are usually treated like cholangiocarcinomas [8]. | Related disorders of Cholangiocarcinoma. Symptoms of the following disorders can be similar to those of cholangiocarcinoma. Comparisons may be useful for a differential diagnosis.Pancreatic cancer can cause similar symptoms to distal cholangiocarcinoma, and it can be difficult to establish whether a cancer is arising from the bile duct or the pancreas in some cases. Cancers arising from the portion of the bile duct located at or near the pancreas are frequently treated in the same way as pancreatic cancers.Hepatocellular cancer is a more common form of primary liver cancer that arises from the liver cells rather than from the bile ducts. It frequently occurs in patients who have chronic liver damage, and is treated differently to cholangiocarcinoma and gallbladder cancer. The appearance on CT and MRI scans of hepatocellular cancer is different to that of biliary tract cancers, and it is usually possible to distinguish between these diagnoses based on imaging studies. In up to 15% of the cases, primary liver tumors may contain features of both hepatocellular cancers and cholangiocarcinomas; these cancers are usually treated like cholangiocarcinomas [8]. | 230 | Cholangiocarcinoma |
nord_230_5 | Diagnosis of Cholangiocarcinoma | A diagnosis of cholangiocarcinoma or gallbladder cancer is made based on identification of characteristic symptoms (if present), a detailed patient history, clinical examination and several specialized tests including blood test, imaging tests and endoscopic procedures. Either CT or MRI scans may be used to assess the tumor size and to look for blockage of the bile ducts and sites of spread [9, 10]. ERCP may be used to insert a stent into a blocked bile duct to relieve jaundice. A biopsy is usually required to confirm the pathologic diagnosis and may be obtained by a CT or endoscopic ultrasound (EUS) guided biopsy [11]. It is critical that genetic testing using next generation sequencing be performed on the obtained biopsy [12]. Some patients with gallbladder cancer are incidentally diagnosed following elective removal of their gallbladder due to gallstones, where the cancer is only detected on pathologic examination. | Diagnosis of Cholangiocarcinoma. A diagnosis of cholangiocarcinoma or gallbladder cancer is made based on identification of characteristic symptoms (if present), a detailed patient history, clinical examination and several specialized tests including blood test, imaging tests and endoscopic procedures. Either CT or MRI scans may be used to assess the tumor size and to look for blockage of the bile ducts and sites of spread [9, 10]. ERCP may be used to insert a stent into a blocked bile duct to relieve jaundice. A biopsy is usually required to confirm the pathologic diagnosis and may be obtained by a CT or endoscopic ultrasound (EUS) guided biopsy [11]. It is critical that genetic testing using next generation sequencing be performed on the obtained biopsy [12]. Some patients with gallbladder cancer are incidentally diagnosed following elective removal of their gallbladder due to gallstones, where the cancer is only detected on pathologic examination. | 230 | Cholangiocarcinoma |
nord_230_6 | Therapies of Cholangiocarcinoma | Treatment
Optimal treatment of biliary tract cancers requires coordinated care of a team of medical professionals, usually including a medical oncologist, surgical oncologist, radiation oncologist, gastroenterologist and pathologist [13].Resectable disease
Surgery: Selected patients with localized disease may be candidates for surgical resection. The surgical approach differs depending on the location of the primary tumor. Intrahepatic cholangiocarcinoma is usually managed with a liver resection, while distal cholangiocarcinomas require a Whipple procedure (pancreaticoduodenectomy) similar to pancreatic cancer, with resection of part of the stomach, pancreas and bile duct. Perihilar cholangiocarcinomas are located where the main bile ducts and blood vessels enter and exit the liver, and so may require a complex surgical procedure involving both liver and bile duct resection [14]. Surgery for gallbladder cancer requires resection of the gallbladder and surrounding liver, and removal of several adjacent lymph nodes [15]. Surgeons should ensure next generation sequencing is performed on obtained resected cancer [12].Chemotherapy: Patients who undergo surgical resection of the tumor may be candidates for post-operative preventative chemotherapy. Due to the relative rarity of gallbladder cancer and cholangiocarcinoma, there is limited data available from clinical trials to guide the use of preventative treatment for these cancers. The benefit of post-operative chemotherapy for cholangiocarcinoma remains a subject under investigation. Nonetheless a large study performed in the UK evaluated the use of Xeloda (capecitabine), an oral chemotherapy agent, as preventative therapy in patients who have undergone surgical resection for cholangiocarcinoma / gallbladder cancer, did not meet its primary endpoint of improving overall survival. [16].Unresectable disease
The majority of patients with biliary tract cancer are diagnosed when the cancer is far too advanced to be removed by surgery. In these cases, chemotherapy is the mainstay of treatment. While chemotherapy in this setting is not curative, it can control and contain the cancer, help patients to live longer and delay or prevent the development of cancer related symptoms. Decision to treat is based on the patient’s level of well-being and presence of other medical conditions. In patients who are well enough, combining two chemotherapy drugs called Gemzar and Platinol (cisplatin) is considered a standard of care [17].Beside chemotherapy, next generation sequencing is critical to be obtained as early as possible. In May 2020, the U.S. Food and Drug Administration (FDA) approved Pemazyre (pemigatinib) as the first treatment for adults with certain types of previously treated, advanced cholangiocarcinoma. Pemazyre works by blocking altered FGFR2 in tumor cells to prevent them from growing and spreading. FGFR2 alterations including fusions have been found in the tumors of approximately 9-14% of cholangiocarcinoma patients [18]. | Therapies of Cholangiocarcinoma. Treatment
Optimal treatment of biliary tract cancers requires coordinated care of a team of medical professionals, usually including a medical oncologist, surgical oncologist, radiation oncologist, gastroenterologist and pathologist [13].Resectable disease
Surgery: Selected patients with localized disease may be candidates for surgical resection. The surgical approach differs depending on the location of the primary tumor. Intrahepatic cholangiocarcinoma is usually managed with a liver resection, while distal cholangiocarcinomas require a Whipple procedure (pancreaticoduodenectomy) similar to pancreatic cancer, with resection of part of the stomach, pancreas and bile duct. Perihilar cholangiocarcinomas are located where the main bile ducts and blood vessels enter and exit the liver, and so may require a complex surgical procedure involving both liver and bile duct resection [14]. Surgery for gallbladder cancer requires resection of the gallbladder and surrounding liver, and removal of several adjacent lymph nodes [15]. Surgeons should ensure next generation sequencing is performed on obtained resected cancer [12].Chemotherapy: Patients who undergo surgical resection of the tumor may be candidates for post-operative preventative chemotherapy. Due to the relative rarity of gallbladder cancer and cholangiocarcinoma, there is limited data available from clinical trials to guide the use of preventative treatment for these cancers. The benefit of post-operative chemotherapy for cholangiocarcinoma remains a subject under investigation. Nonetheless a large study performed in the UK evaluated the use of Xeloda (capecitabine), an oral chemotherapy agent, as preventative therapy in patients who have undergone surgical resection for cholangiocarcinoma / gallbladder cancer, did not meet its primary endpoint of improving overall survival. [16].Unresectable disease
The majority of patients with biliary tract cancer are diagnosed when the cancer is far too advanced to be removed by surgery. In these cases, chemotherapy is the mainstay of treatment. While chemotherapy in this setting is not curative, it can control and contain the cancer, help patients to live longer and delay or prevent the development of cancer related symptoms. Decision to treat is based on the patient’s level of well-being and presence of other medical conditions. In patients who are well enough, combining two chemotherapy drugs called Gemzar and Platinol (cisplatin) is considered a standard of care [17].Beside chemotherapy, next generation sequencing is critical to be obtained as early as possible. In May 2020, the U.S. Food and Drug Administration (FDA) approved Pemazyre (pemigatinib) as the first treatment for adults with certain types of previously treated, advanced cholangiocarcinoma. Pemazyre works by blocking altered FGFR2 in tumor cells to prevent them from growing and spreading. FGFR2 alterations including fusions have been found in the tumors of approximately 9-14% of cholangiocarcinoma patients [18]. | 230 | Cholangiocarcinoma |
nord_231_0 | Overview of Cholera | Cholera is an acute infectious disease caused by the bacterium vibrio cholerae, which lives and multiples (colonizes) in the small intestine but does not destroy or invade the intestinal tissue (noninvasive). The major symptom of cholera is massive watery diarrhea that occurs because of a toxin secreted by the bacteria that stimulates the cells of the small intestine to secrete fluid. There are several strains of V. cholerae and the severity of the disease is based on the particular infectious strain.Cholera is not a difficult disease to treat and most people recover well with appropriate oral fluid replacement (hydration). However, if the disease goes untreated, it can rapidly lead to shock, as a result of fluid and electrolyte loss, and to life-threatening complications. | Overview of Cholera. Cholera is an acute infectious disease caused by the bacterium vibrio cholerae, which lives and multiples (colonizes) in the small intestine but does not destroy or invade the intestinal tissue (noninvasive). The major symptom of cholera is massive watery diarrhea that occurs because of a toxin secreted by the bacteria that stimulates the cells of the small intestine to secrete fluid. There are several strains of V. cholerae and the severity of the disease is based on the particular infectious strain.Cholera is not a difficult disease to treat and most people recover well with appropriate oral fluid replacement (hydration). However, if the disease goes untreated, it can rapidly lead to shock, as a result of fluid and electrolyte loss, and to life-threatening complications. | 231 | Cholera |
nord_231_1 | Symptoms of Cholera | The symptoms of cholera vary according to the severity of the disease. Some infected individuals may only experience a few days of mild diarrhea. Others may have more serious symptoms and prolonged diarrhea may be so severe that there is excessive fluid loss leading to shock. Rapid onset of life- threatening complications may occur in very severe cases.The initial symptoms of cholera may include sudden painless diarrhea and vomiting. Diarrhea becomes progressively more watery and large volumes of fluid, sodium, chloride, potassium, and bicarbonate (electrolytes) are lost. Subsequent symptoms are the direct result of the fluid loss (dehydration) and electrolyte imbalance. These may include intense thirst, decreased urine output, muscle cramps, and/or general weakness. Abnormally low blood pressure (hypotension) and potassium (hypokalemia) are common. Excessive amounts of acid may accumulate in the blood and body tissues (acidosis) and shock may develop if treatment is not administered. Kidney failure may occur, but generally responds to fluid replacement. | Symptoms of Cholera. The symptoms of cholera vary according to the severity of the disease. Some infected individuals may only experience a few days of mild diarrhea. Others may have more serious symptoms and prolonged diarrhea may be so severe that there is excessive fluid loss leading to shock. Rapid onset of life- threatening complications may occur in very severe cases.The initial symptoms of cholera may include sudden painless diarrhea and vomiting. Diarrhea becomes progressively more watery and large volumes of fluid, sodium, chloride, potassium, and bicarbonate (electrolytes) are lost. Subsequent symptoms are the direct result of the fluid loss (dehydration) and electrolyte imbalance. These may include intense thirst, decreased urine output, muscle cramps, and/or general weakness. Abnormally low blood pressure (hypotension) and potassium (hypokalemia) are common. Excessive amounts of acid may accumulate in the blood and body tissues (acidosis) and shock may develop if treatment is not administered. Kidney failure may occur, but generally responds to fluid replacement. | 231 | Cholera |
nord_231_2 | Causes of Cholera | Cholera is caused by the bacterium vibrio cholerae which is a rod-shaped gram negative organism. There are several different types of this bacteria which can produce mild or more severe forms of the disease. The symptoms of cholera develop due to the release of a toxin (Vibrio c. 01) by the bacteria. | Causes of Cholera. Cholera is caused by the bacterium vibrio cholerae which is a rod-shaped gram negative organism. There are several different types of this bacteria which can produce mild or more severe forms of the disease. The symptoms of cholera develop due to the release of a toxin (Vibrio c. 01) by the bacteria. | 231 | Cholera |
nord_231_3 | Affects of Cholera | Outbreaks of cholera are typically limited to specific geographic areas (endemic) in India and parts of the Middle East, Asia, South America, and Africa. The disease affects males and females in equal numbers. Children are more susceptible to cholera than adults, especially those children under the age of five years. Major outbreaks of cholera usually occur during the warmest part of the year. Cholera occasionally spreads to Europe, Japan, Australia, and South America where epidemics can occur any time of the year and affect persons of all ages equally.Cholera is primarily a waterborne disease. During epidemics, cholera may spread rapidly as increasing numbers of affected individuals excrete large volumes of infected stool. Drinking, washing, and cooking water become rapidly contaminated with Vibrio cholerae bacteria, especially when sanitation conditions are substandard. During the 1990s cholera became endemic in South America and some cases were reported in the United States.The symptoms of cholera tend to be more severe in those people with Type O blood; those with Type AB blood tend to get a less severe form of the disease. The exact reason for this difference is not fully understood. | Affects of Cholera. Outbreaks of cholera are typically limited to specific geographic areas (endemic) in India and parts of the Middle East, Asia, South America, and Africa. The disease affects males and females in equal numbers. Children are more susceptible to cholera than adults, especially those children under the age of five years. Major outbreaks of cholera usually occur during the warmest part of the year. Cholera occasionally spreads to Europe, Japan, Australia, and South America where epidemics can occur any time of the year and affect persons of all ages equally.Cholera is primarily a waterborne disease. During epidemics, cholera may spread rapidly as increasing numbers of affected individuals excrete large volumes of infected stool. Drinking, washing, and cooking water become rapidly contaminated with Vibrio cholerae bacteria, especially when sanitation conditions are substandard. During the 1990s cholera became endemic in South America and some cases were reported in the United States.The symptoms of cholera tend to be more severe in those people with Type O blood; those with Type AB blood tend to get a less severe form of the disease. The exact reason for this difference is not fully understood. | 231 | Cholera |
nord_231_4 | Related disorders of Cholera | Symptoms of the following disorders can be similar to those of cholera. Comparisons may be useful for a differential diagnosis:Escherichia coli are bacteria found in the intestines of humans and many animals. They usually do not cause disease (nonpathogenic) but certain strains may cause acute inflammation in some cases. When these infections occur in the small intestine, symptoms may include bloody and watery diarrhea accompanied by fever. When severe infection occurs in newborns, it is called Winckel's Disease and may cause overwhelming infection of the blood stream (septicemia). An outbreak of E. coli infection from under cooked hamburger meat occurred in the Unites States during the early 1990's. Several children died from this infection; others experience varying symptoms.Salmonellosis is a common form of infectious inflammation of the small intestine (gastroenteritis). It is caused by the ingestion of food that has been contaminated by a certain species of Salmonella bacteria. Symptoms typically begin approximately 6 to 48 hours after infection and may include fever, watery diarrhea, abdominal pain and discomfort, nausea, and/or vomiting. The symptoms usually last for less than one week. However, diarrhea and fever may persist for up to 2 weeks.Shigellosis (Bacterial Dysentery) is an infectious disease caused by the Shigella organism. The symptoms typically appear 1 to 4 days after infection and may include sudden high fever, irritability, drowsiness, profound loss of appetite (anorexia), diarrhea, and/or abdominal pain. The disease is spread by contaminated food and water and by the bite of certain flies. Shigellosis usually infects small children and the symptoms are more severe in children than in adults. Antibiotics and fluid replacement are used to treat Shigellosis.Typhoid Fever is an acute systemic infection caused by the bacteria Salmonella typhi. The major symptoms reflect the involvement of the digestive, blood, neurological, and respiratory systems. The symptoms typically begin suddenly and may include fever, headache, muscle pain (myalgia), and/or a general feeling of ill health (malaise). The fever is usually high and may occur along with an abnormally slow heartbeat (bradycardia). Diarrhea is common, but constipation may also occur. Neurological symptoms may include seizures, delirium, and psychotic episodes. Complications of Typhoid Fever are common and may be life-threatening. (For more information on this disorder, choose “Typhoid Fever” as your search term in the Rare Disease Database.)Pancreatic Cholera is a rare gastrointestinal disease and is not a bacterial disease, despite its name. It is characterized by watery diarrhea, abnormally low levels of potassium (hypokalemia), and the abnormal accumulation of acid in the blood and other tissues of the body. Frequently the disorder is due to a pancreatic tumor (vipoma) that secretes a substance known as vasoactive intestinal polypeptide (VIP). The episodes of diarrhea in association with the profound loss of potassium and fluids may have life- threatening complications. | Related disorders of Cholera. Symptoms of the following disorders can be similar to those of cholera. Comparisons may be useful for a differential diagnosis:Escherichia coli are bacteria found in the intestines of humans and many animals. They usually do not cause disease (nonpathogenic) but certain strains may cause acute inflammation in some cases. When these infections occur in the small intestine, symptoms may include bloody and watery diarrhea accompanied by fever. When severe infection occurs in newborns, it is called Winckel's Disease and may cause overwhelming infection of the blood stream (septicemia). An outbreak of E. coli infection from under cooked hamburger meat occurred in the Unites States during the early 1990's. Several children died from this infection; others experience varying symptoms.Salmonellosis is a common form of infectious inflammation of the small intestine (gastroenteritis). It is caused by the ingestion of food that has been contaminated by a certain species of Salmonella bacteria. Symptoms typically begin approximately 6 to 48 hours after infection and may include fever, watery diarrhea, abdominal pain and discomfort, nausea, and/or vomiting. The symptoms usually last for less than one week. However, diarrhea and fever may persist for up to 2 weeks.Shigellosis (Bacterial Dysentery) is an infectious disease caused by the Shigella organism. The symptoms typically appear 1 to 4 days after infection and may include sudden high fever, irritability, drowsiness, profound loss of appetite (anorexia), diarrhea, and/or abdominal pain. The disease is spread by contaminated food and water and by the bite of certain flies. Shigellosis usually infects small children and the symptoms are more severe in children than in adults. Antibiotics and fluid replacement are used to treat Shigellosis.Typhoid Fever is an acute systemic infection caused by the bacteria Salmonella typhi. The major symptoms reflect the involvement of the digestive, blood, neurological, and respiratory systems. The symptoms typically begin suddenly and may include fever, headache, muscle pain (myalgia), and/or a general feeling of ill health (malaise). The fever is usually high and may occur along with an abnormally slow heartbeat (bradycardia). Diarrhea is common, but constipation may also occur. Neurological symptoms may include seizures, delirium, and psychotic episodes. Complications of Typhoid Fever are common and may be life-threatening. (For more information on this disorder, choose “Typhoid Fever” as your search term in the Rare Disease Database.)Pancreatic Cholera is a rare gastrointestinal disease and is not a bacterial disease, despite its name. It is characterized by watery diarrhea, abnormally low levels of potassium (hypokalemia), and the abnormal accumulation of acid in the blood and other tissues of the body. Frequently the disorder is due to a pancreatic tumor (vipoma) that secretes a substance known as vasoactive intestinal polypeptide (VIP). The episodes of diarrhea in association with the profound loss of potassium and fluids may have life- threatening complications. | 231 | Cholera |
nord_231_5 | Diagnosis of Cholera | Diagnosis of Cholera. | 231 | Cholera |
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nord_231_6 | Therapies of Cholera | The diagnosis of cholera is confirmed by clinical evaluation and the isolation of the V. cholerae from cultures grown with samples of fresh stool from an infected individual.The symptoms of mild or uncomplicated cases of cholera resolve on their own (spontaneously) within 3 to 6 days of onset. The bacteria usually disappear from the gastrointestinal system within 2 weeks.Most people with cholera require the replacement of fluids that are lost due to prolonged diarrhea. If fluids are started early, most affected individuals can replace fluids orally. The administration of intravenous fluids is necessary in very severe cases of cholera and in people who produce more than seven liters of stool volume a day. If shock occurs or if oral fluid intake is not possible (i.e., excessive vomiting), intravenous fluid replacement is essential. A variety of fluid replacements that contain salts, glucose, electrolytes, and/or bicarbonate are available, some in packet form (i.e., Pedialyte, Rice solution, Ricelyte, and WHO/UNICEF solution). These can be administered easily even without medical personnel.The aim of fluid replacement is to restore electrolyte balance, reverse dehydration, and to restore normal blood pressure. Plasma and related products, and drugs that raise blood pressure are useless in the treatment of cholera. After the initial crisis is over, patients may continue intravenous fluid and salt replacement, or these fluids may be given by mouth.Antibiotics will shorten the course of cholera and usually prevent severe illness if administered early. Tetracycline is the drug of choice and ampicillin is an acceptable substitute for pregnant women and children. The drug Furazolidone is usually effective against resistant strains of the bacteria.The most important methods of prevention and control of cholera are clean water supplies and adequate sewage disposal. Water supplies must be purified and human waste must be disposed of properly. Individuals in areas where cholera is endemic should boil all water and avoid eating uncooked vegetables and ice.People living in endemic areas usually develop an immunity to the cholera bacterium. Travelers to these areas should be vaccinated against the disease. Vaccines against cholera are available but are not 100 percent effective; booster injections are required every 6 months. Tetracycline may be administered to prevent the disease (prophylaxis) if a person is exposed to contaminated food or water. Travelers to South America, Middle East, Asia, and Africa should check with the Centers for Disease Control (CDC) to determine areas of endemic cholera and availability of the cholera vaccine. | Therapies of Cholera. The diagnosis of cholera is confirmed by clinical evaluation and the isolation of the V. cholerae from cultures grown with samples of fresh stool from an infected individual.The symptoms of mild or uncomplicated cases of cholera resolve on their own (spontaneously) within 3 to 6 days of onset. The bacteria usually disappear from the gastrointestinal system within 2 weeks.Most people with cholera require the replacement of fluids that are lost due to prolonged diarrhea. If fluids are started early, most affected individuals can replace fluids orally. The administration of intravenous fluids is necessary in very severe cases of cholera and in people who produce more than seven liters of stool volume a day. If shock occurs or if oral fluid intake is not possible (i.e., excessive vomiting), intravenous fluid replacement is essential. A variety of fluid replacements that contain salts, glucose, electrolytes, and/or bicarbonate are available, some in packet form (i.e., Pedialyte, Rice solution, Ricelyte, and WHO/UNICEF solution). These can be administered easily even without medical personnel.The aim of fluid replacement is to restore electrolyte balance, reverse dehydration, and to restore normal blood pressure. Plasma and related products, and drugs that raise blood pressure are useless in the treatment of cholera. After the initial crisis is over, patients may continue intravenous fluid and salt replacement, or these fluids may be given by mouth.Antibiotics will shorten the course of cholera and usually prevent severe illness if administered early. Tetracycline is the drug of choice and ampicillin is an acceptable substitute for pregnant women and children. The drug Furazolidone is usually effective against resistant strains of the bacteria.The most important methods of prevention and control of cholera are clean water supplies and adequate sewage disposal. Water supplies must be purified and human waste must be disposed of properly. Individuals in areas where cholera is endemic should boil all water and avoid eating uncooked vegetables and ice.People living in endemic areas usually develop an immunity to the cholera bacterium. Travelers to these areas should be vaccinated against the disease. Vaccines against cholera are available but are not 100 percent effective; booster injections are required every 6 months. Tetracycline may be administered to prevent the disease (prophylaxis) if a person is exposed to contaminated food or water. Travelers to South America, Middle East, Asia, and Africa should check with the Centers for Disease Control (CDC) to determine areas of endemic cholera and availability of the cholera vaccine. | 231 | Cholera |
nord_232_0 | Overview of Cholesteryl Ester Storage Disease | Summary
Cholesteryl ester storage disease (CESD) is a type of lysosomal acid lipase (LAL) deficiency; a rare genetic disorder characterized by a deficiency of the lysosomal acid lipase (LIPA or LAL) enzyme. This enzyme is essential for hydrolysis of triglycerides and cholesteryl esters in lysosomes. Deficiency of the LIPA enzyme causes accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body, potentially causing a variety of symptoms. In the liver, the consequences are abnormally enlarged liver (hepatomegaly) due to hepatic steatosis (fatty liver) and fibrosis that can lead to micronodular cirrhosis. Some individuals may not be diagnosed with CESD until adulthood. CESD is caused by changes (pathogenic variants or mutations) in the lysosomal acid lipase (LIPA) gene and is inherited in an autosomal recessive pattern.Introduction
CESD and Wolman disease are the two types of lysosomal acid lipase deficiency. LIPA gene variants that cause CESD result in some enzyme activity, whereas LIPA gene variants that cause Wolman disease produce an enzyme with no residual activity or no enzyme at all. Genetic and biochemical evidence indicates that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity. | Overview of Cholesteryl Ester Storage Disease. Summary
Cholesteryl ester storage disease (CESD) is a type of lysosomal acid lipase (LAL) deficiency; a rare genetic disorder characterized by a deficiency of the lysosomal acid lipase (LIPA or LAL) enzyme. This enzyme is essential for hydrolysis of triglycerides and cholesteryl esters in lysosomes. Deficiency of the LIPA enzyme causes accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body, potentially causing a variety of symptoms. In the liver, the consequences are abnormally enlarged liver (hepatomegaly) due to hepatic steatosis (fatty liver) and fibrosis that can lead to micronodular cirrhosis. Some individuals may not be diagnosed with CESD until adulthood. CESD is caused by changes (pathogenic variants or mutations) in the lysosomal acid lipase (LIPA) gene and is inherited in an autosomal recessive pattern.Introduction
CESD and Wolman disease are the two types of lysosomal acid lipase deficiency. LIPA gene variants that cause CESD result in some enzyme activity, whereas LIPA gene variants that cause Wolman disease produce an enzyme with no residual activity or no enzyme at all. Genetic and biochemical evidence indicates that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity. | 232 | Cholesteryl Ester Storage Disease |
nord_232_1 | Symptoms of Cholesteryl Ester Storage Disease | The symptoms and severity of CESD are highly variable. Some individuals may develop symptoms during childhood; others may have extremely mild cases that cause few symptoms. Still other individuals may not have any noticeable symptoms (asymptomatic) and may go undiagnosed until well into adulthood. It is important to note that affected individuals will not have all of the symptoms discussed below. The disorder often goes misdiagnosed or undiagnosed, making it difficult to determine its true frequency in the general population.CESD is characterized by alterations of blood lipoprotein profile; patients present hypercholesterolemia, hypertriglyceridemia, HDL deficiency with abnormal lipid deposition in many organs. The primary finding in many patients, and sometimes the only clinical sign, is thus a mixed hyperlipidemia with low HDL-cholesterol levels. Patients normally present with hepatomegaly, often apparent at birth or during early childhood. In rare cases, it may not become apparent until the second decade of life. Hepatomegaly usually becomes progressively worse, eventually causing scarring (fibrosis) of the liver. In approximately one-third of patients, the spleen may also be enlarged (splenomegaly).In most patients, CESD is considered a benign condition, but in some patients, significant complications may eventually develop including fatty liver (liver steatosis), fibrosis and finally micronodular cirrhosis with liver failure and esophageal varices due to altered hepatic venous circulation. The vessels swell and sometimes may rupture, causing potentially life-threatening bleeding. Abnormal enlargement of the adrenal glands (adrenomegaly) may also occur in few individuals. The adrenal glands are located on top of the kidneys and produce two hormones called epinephrine and norepinephrine. Other hormones produced by the adrenal glands help to regulate the fluid and electrolyte balance in the body. In rare cases, hardening of adrenal gland tissue due to the accumulation of calcium (calcification) may occur, but this finding is much more common in Wolman disease than in CESD. | Symptoms of Cholesteryl Ester Storage Disease. The symptoms and severity of CESD are highly variable. Some individuals may develop symptoms during childhood; others may have extremely mild cases that cause few symptoms. Still other individuals may not have any noticeable symptoms (asymptomatic) and may go undiagnosed until well into adulthood. It is important to note that affected individuals will not have all of the symptoms discussed below. The disorder often goes misdiagnosed or undiagnosed, making it difficult to determine its true frequency in the general population.CESD is characterized by alterations of blood lipoprotein profile; patients present hypercholesterolemia, hypertriglyceridemia, HDL deficiency with abnormal lipid deposition in many organs. The primary finding in many patients, and sometimes the only clinical sign, is thus a mixed hyperlipidemia with low HDL-cholesterol levels. Patients normally present with hepatomegaly, often apparent at birth or during early childhood. In rare cases, it may not become apparent until the second decade of life. Hepatomegaly usually becomes progressively worse, eventually causing scarring (fibrosis) of the liver. In approximately one-third of patients, the spleen may also be enlarged (splenomegaly).In most patients, CESD is considered a benign condition, but in some patients, significant complications may eventually develop including fatty liver (liver steatosis), fibrosis and finally micronodular cirrhosis with liver failure and esophageal varices due to altered hepatic venous circulation. The vessels swell and sometimes may rupture, causing potentially life-threatening bleeding. Abnormal enlargement of the adrenal glands (adrenomegaly) may also occur in few individuals. The adrenal glands are located on top of the kidneys and produce two hormones called epinephrine and norepinephrine. Other hormones produced by the adrenal glands help to regulate the fluid and electrolyte balance in the body. In rare cases, hardening of adrenal gland tissue due to the accumulation of calcium (calcification) may occur, but this finding is much more common in Wolman disease than in CESD. | 232 | Cholesteryl Ester Storage Disease |
nord_232_2 | Causes of Cholesteryl Ester Storage Disease | CESD is caused by pathogenic variants in the lysosomal acid lipase (LIPA) gene. The LIPA gene contains instructions for producing the enzyme lysosomal lipase acid. This enzyme is essential for breaking down (metabolizing) certain fats in the body, especially cholesteryl esters (a form of cholesterol) and to a lesser degree triglycerides. Without proper levels of this enzyme, these fats abnormally accumulate in and damage various tissues and organs of the body. Variants in the LIPA gene result deficient levels of active, functional LIPA enzyme. There is no direct linear relation between residual LAL activity and the severity of the disease.CESD is inherited as an autosomal recessive condition. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. | Causes of Cholesteryl Ester Storage Disease. CESD is caused by pathogenic variants in the lysosomal acid lipase (LIPA) gene. The LIPA gene contains instructions for producing the enzyme lysosomal lipase acid. This enzyme is essential for breaking down (metabolizing) certain fats in the body, especially cholesteryl esters (a form of cholesterol) and to a lesser degree triglycerides. Without proper levels of this enzyme, these fats abnormally accumulate in and damage various tissues and organs of the body. Variants in the LIPA gene result deficient levels of active, functional LIPA enzyme. There is no direct linear relation between residual LAL activity and the severity of the disease.CESD is inherited as an autosomal recessive condition. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.Parents who are close 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. | 232 | Cholesteryl Ester Storage Disease |
nord_232_3 | Affects of Cholesteryl Ester Storage Disease | CESD affects males and females in equal numbers. Approximately 50 cases have been reported in the medical literature. It is likely that there are more patients with CESD who have been misdiagnosed with other conditions. | Affects of Cholesteryl Ester Storage Disease. CESD affects males and females in equal numbers. Approximately 50 cases have been reported in the medical literature. It is likely that there are more patients with CESD who have been misdiagnosed with other conditions. | 232 | Cholesteryl Ester Storage Disease |
nord_232_4 | Related disorders of Cholesteryl Ester Storage Disease | Symptoms of the following disorders can be similar to those of cholesteryl ester storage disease. Comparisons may be useful for a differential diagnosis.Wolman disease is a rare genetic disorder characterized by complete absence of the lysosomal acid lipase enzyme. It is often fatal within the first six months of life. Without the LIPA enzyme, certain lipids may abnormally accumulate in the tissues and organs of the body causing a variety of symptoms. Wolman disease causes adrenal calcifications and may lead to bloating or swelling of the stomach (abdominal distention), vomiting and significant enlargement of the liver or spleen (hepatosplenomegaly). Life-threatening complications often develop during early childhood. Wolman disease is caused by different variants in the LIPA gene that causes CESD. Wolman disease is inherited in an autosomal recessive pattern. (For more information on this disorder, choose “Wolman disease” as your search term in the Rare Disease Database.)Niemann-Pick disease (NPD) is a group of rare inherited disorders of fat metabolism. At least five types of Niemann-Pick disease have been identified (NPD types A, B, C, D, and E). Symptoms of types A and B occur as a result of a deficiency of the enzyme acid sphingomyelinase (ASM), which is needed to break down sphingomyelin, a fatty substance found mostly in the brain and nervous system. This deficiency results in abnormal accumulation of excessive amounts of sphingomyelin in many organs of the body such as the liver, spleen and brain. Symptoms of type C occur because of impaired trafficking of large molecules within cells, which results in the accumulation of excessive amounts of cholesterol and other lipids (glycosphingolipids) in tissues throughout the body. The metabolic defect in type C can lead to a secondary reduction in ASM activity in some cells. Symptoms common to all types of NPD include yellow discoloration of the skin, eyes and/or mucous membranes (jaundice), progressive loss of motor skills, feeding difficulties, learning disabilities and hepatosplenomegaly. The different types of NPD are inherited in an autosomal recessive pattern. For more information on this disorder, choose “Niemann Pick” as your search term in the Rare Disease Database.Chanarin Dorfman syndrome is a rare genetic disorder of fat (lipid) metabolism. It is characterized by scaly skin (ichthyosis), degeneration of the muscles (myopathy) and abnormal white blood cells with small spaces (vacuoles) filled with fat (lipids). Additional symptoms may occur including hearing loss, vision abnormalities, hepatomegaly and liver steatosis. Cognitive decline may occur in some affected individuals. Chanarin Dorfman syndrome is inherited in an autosomal recessive pattern. (For more information on this disorder, choose “Chanarin Dorfman” as your search term in the Rare Disease Database.)There are several types of metabolic disorders in which secondary accumulation of certain fats (triglycerides) occur in the body. These disorders include galactosemia, fructose intolerance and specific disorders amino acid metabolism. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | Related disorders of Cholesteryl Ester Storage Disease. Symptoms of the following disorders can be similar to those of cholesteryl ester storage disease. Comparisons may be useful for a differential diagnosis.Wolman disease is a rare genetic disorder characterized by complete absence of the lysosomal acid lipase enzyme. It is often fatal within the first six months of life. Without the LIPA enzyme, certain lipids may abnormally accumulate in the tissues and organs of the body causing a variety of symptoms. Wolman disease causes adrenal calcifications and may lead to bloating or swelling of the stomach (abdominal distention), vomiting and significant enlargement of the liver or spleen (hepatosplenomegaly). Life-threatening complications often develop during early childhood. Wolman disease is caused by different variants in the LIPA gene that causes CESD. Wolman disease is inherited in an autosomal recessive pattern. (For more information on this disorder, choose “Wolman disease” as your search term in the Rare Disease Database.)Niemann-Pick disease (NPD) is a group of rare inherited disorders of fat metabolism. At least five types of Niemann-Pick disease have been identified (NPD types A, B, C, D, and E). Symptoms of types A and B occur as a result of a deficiency of the enzyme acid sphingomyelinase (ASM), which is needed to break down sphingomyelin, a fatty substance found mostly in the brain and nervous system. This deficiency results in abnormal accumulation of excessive amounts of sphingomyelin in many organs of the body such as the liver, spleen and brain. Symptoms of type C occur because of impaired trafficking of large molecules within cells, which results in the accumulation of excessive amounts of cholesterol and other lipids (glycosphingolipids) in tissues throughout the body. The metabolic defect in type C can lead to a secondary reduction in ASM activity in some cells. Symptoms common to all types of NPD include yellow discoloration of the skin, eyes and/or mucous membranes (jaundice), progressive loss of motor skills, feeding difficulties, learning disabilities and hepatosplenomegaly. The different types of NPD are inherited in an autosomal recessive pattern. For more information on this disorder, choose “Niemann Pick” as your search term in the Rare Disease Database.Chanarin Dorfman syndrome is a rare genetic disorder of fat (lipid) metabolism. It is characterized by scaly skin (ichthyosis), degeneration of the muscles (myopathy) and abnormal white blood cells with small spaces (vacuoles) filled with fat (lipids). Additional symptoms may occur including hearing loss, vision abnormalities, hepatomegaly and liver steatosis. Cognitive decline may occur in some affected individuals. Chanarin Dorfman syndrome is inherited in an autosomal recessive pattern. (For more information on this disorder, choose “Chanarin Dorfman” as your search term in the Rare Disease Database.)There are several types of metabolic disorders in which secondary accumulation of certain fats (triglycerides) occur in the body. These disorders include galactosemia, fructose intolerance and specific disorders amino acid metabolism. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | 232 | Cholesteryl Ester Storage Disease |
nord_232_5 | Diagnosis of Cholesteryl Ester Storage Disease | A diagnosis of CESD may be suspected based upon identification of characteristic symptoms such as abnormally enlarged liver. A diagnosis may be confirmed by a thorough clinical evaluation, a detail patient history (including family history) and specialized tests that reveal deficient activity of the LIPA enzyme in certain cells and tissues of the body. Testing for CESD is easy to perform and reliable through the measurement of enzyme activity in circulating leukocytes using dry blood spot (DBS) technology. In these cells, LAL activity is more severely depressed than in the body. Molecular genetic testing for variants in the LIPA gene is also available. This is usually a two-step procedure where testing for the highly prevalent E8SJM variant is done first and, if needed, sequencing of the LIPA gene is the second step. | Diagnosis of Cholesteryl Ester Storage Disease. A diagnosis of CESD may be suspected based upon identification of characteristic symptoms such as abnormally enlarged liver. A diagnosis may be confirmed by a thorough clinical evaluation, a detail patient history (including family history) and specialized tests that reveal deficient activity of the LIPA enzyme in certain cells and tissues of the body. Testing for CESD is easy to perform and reliable through the measurement of enzyme activity in circulating leukocytes using dry blood spot (DBS) technology. In these cells, LAL activity is more severely depressed than in the body. Molecular genetic testing for variants in the LIPA gene is also available. This is usually a two-step procedure where testing for the highly prevalent E8SJM variant is done first and, if needed, sequencing of the LIPA gene is the second step. | 232 | Cholesteryl Ester Storage Disease |
nord_232_6 | Therapies of Cholesteryl Ester Storage Disease | Treatment
In 2015, the U.S. Food and Drug Administration (FDA) approved Kanuma (sebelipase alfa) as the first treatment for lysosomal acid lipase (LAL) deficiency.A hypolipidemic diet and statins are other therapeutic tools used against CESD. Among hypolipidemic agents, also fibrates, cholestyramine, ezetimibe can be used. Other treatment of CESD is directed toward the specific symptoms that are apparent in each individual. Some individuals have been treated with a hypolipidic diet and statins that reduce plasma cholesterol levels. The combination of diet and drug administration has led to dramatic reductions in the levels of lipids such as cholesterol and triglycerides in the blood of affected individuals.A few individuals with CESD who developed chronic liver disease have been treated with a liver transplant with positive results. Specific therapeutic procedures such as a liver transplant depend upon numerous factors, such as disease severity, an individual’s age and general health, and other factors. Decisions concerning specific 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 their case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Cholesteryl Ester Storage Disease. Treatment
In 2015, the U.S. Food and Drug Administration (FDA) approved Kanuma (sebelipase alfa) as the first treatment for lysosomal acid lipase (LAL) deficiency.A hypolipidemic diet and statins are other therapeutic tools used against CESD. Among hypolipidemic agents, also fibrates, cholestyramine, ezetimibe can be used. Other treatment of CESD is directed toward the specific symptoms that are apparent in each individual. Some individuals have been treated with a hypolipidic diet and statins that reduce plasma cholesterol levels. The combination of diet and drug administration has led to dramatic reductions in the levels of lipids such as cholesterol and triglycerides in the blood of affected individuals.A few individuals with CESD who developed chronic liver disease have been treated with a liver transplant with positive results. Specific therapeutic procedures such as a liver transplant depend upon numerous factors, such as disease severity, an individual’s age and general health, and other factors. Decisions concerning specific 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 their case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | 232 | Cholesteryl Ester Storage Disease |
nord_233_0 | Overview of Chondrocalcinosis 2 | SummaryChondrocalcinosis 2 (CCAL2) is a genetic type of calcium pyrophosphate deposition disease (CPDD), a metabolic disorder characterized by deposits of calcium pyrophosphate dihydrate crystals (CPPD) in joint cartilage and eventual damage to affected joints. The symptoms of CCAL2 include swelling, stiffness, pain, and loss of function of the affected joints. The knee is most commonly affected area. CCAL2 is an autosomal dominant genetic disorder that is usually diagnosed in early adulthood. The non-genetic forms of CPDD are much more common, and typically cause arthritis in patients over the age of 60. | Overview of Chondrocalcinosis 2. SummaryChondrocalcinosis 2 (CCAL2) is a genetic type of calcium pyrophosphate deposition disease (CPDD), a metabolic disorder characterized by deposits of calcium pyrophosphate dihydrate crystals (CPPD) in joint cartilage and eventual damage to affected joints. The symptoms of CCAL2 include swelling, stiffness, pain, and loss of function of the affected joints. The knee is most commonly affected area. CCAL2 is an autosomal dominant genetic disorder that is usually diagnosed in early adulthood. The non-genetic forms of CPDD are much more common, and typically cause arthritis in patients over the age of 60. | 233 | Chondrocalcinosis 2 |
nord_233_1 | Symptoms of Chondrocalcinosis 2 | The symptoms of CCAL2 usually begin as acute, recurring attacks of pain, swelling warmth and redness in one or more joints. Other affected people have swelling, stiffness, and pain with little or no inflammation. in the joints A knee, wrist, hip, or shoulder is most frequently affected, although any joint of the body may be involved. Acute episodes can last for days to weeks, and symptoms may subside without treatment. Calcium pyrophosphate (CPP) crystal deposits may accumulate around the bones of the spine (vertebrae) and cause back or neck pain and/or loss of mobility. Many patients with CPDD develop chronic arthritis which can resemble osteoarthritis. | Symptoms of Chondrocalcinosis 2. The symptoms of CCAL2 usually begin as acute, recurring attacks of pain, swelling warmth and redness in one or more joints. Other affected people have swelling, stiffness, and pain with little or no inflammation. in the joints A knee, wrist, hip, or shoulder is most frequently affected, although any joint of the body may be involved. Acute episodes can last for days to weeks, and symptoms may subside without treatment. Calcium pyrophosphate (CPP) crystal deposits may accumulate around the bones of the spine (vertebrae) and cause back or neck pain and/or loss of mobility. Many patients with CPDD develop chronic arthritis which can resemble osteoarthritis. | 233 | Chondrocalcinosis 2 |
nord_233_2 | Causes of Chondrocalcinosis 2 | CCAL2 is caused by presumed gain-of-function mutations in the ANKH gene.The protein produced by the ANKH gene seems to be involved in cellular transport of inorganic pyrophosphate (PPi), and mutations in ANKH have been shown to have a significant effect on the regulation of PPi levels within the cells (intracellular) and outside the cells (extracellular). When ANKH activity is increased, levels of PPi accumulate in cartilage, complex with calcium, and form calcium pyrophosphate (CPP) crystals.In most cases, CCAL2 is inherited as an autosomal dominant genetic trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.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. The symptoms of CCAL2 are thought to be more severe in those affected individuals who carry two abnormal genes for this disorder (homozygotes), one from each parent. Those who have only one abnormal gene (heterozygotes) are thought to experience less severe symptoms. | Causes of Chondrocalcinosis 2. CCAL2 is caused by presumed gain-of-function mutations in the ANKH gene.The protein produced by the ANKH gene seems to be involved in cellular transport of inorganic pyrophosphate (PPi), and mutations in ANKH have been shown to have a significant effect on the regulation of PPi levels within the cells (intracellular) and outside the cells (extracellular). When ANKH activity is increased, levels of PPi accumulate in cartilage, complex with calcium, and form calcium pyrophosphate (CPP) crystals.In most cases, CCAL2 is inherited as an autosomal dominant genetic trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.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. The symptoms of CCAL2 are thought to be more severe in those affected individuals who carry two abnormal genes for this disorder (homozygotes), one from each parent. Those who have only one abnormal gene (heterozygotes) are thought to experience less severe symptoms. | 233 | Chondrocalcinosis 2 |
nord_233_3 | Affects of Chondrocalcinosis 2 | CCAL2 is a rare disorder. Eight families have been described in the medical literature. Some studies indicate a greater prevalence of non-genetic CPDD in females, but this is based on weak evidence. There is no known ethnic predilection. | Affects of Chondrocalcinosis 2. CCAL2 is a rare disorder. Eight families have been described in the medical literature. Some studies indicate a greater prevalence of non-genetic CPDD in females, but this is based on weak evidence. There is no known ethnic predilection. | 233 | Chondrocalcinosis 2 |
nord_233_4 | Related disorders of Chondrocalcinosis 2 | Symptoms of the following disorders can be similar to those of CCAL2. Comparisons may be useful for a differential diagnosis:Sporadic CPDD typically occurs in people over age 60, but causes similar symptoms of acute and chronic arthritis. The non-genetic forms may also occur in association with certain metabolic conditions such as hyperparathyroidism, familial hypocalciuric hypercalcemia, Wilson’s disease, Bartter’s syndrome, hypophosphatasia, hypomagnesemia, and hereditary hemochromatosis. Gout is a common metabolic disorder characterized by an inborn error of uric acid (purine) metabolism. Excessive uric acid may form crystals composed of monosodium urate, that are deposited in the joints, and other areas of the body. The large toe is the most common site for the accumulation of crystals. Symptoms may include sharp pain in the toe or other affected area, joint swelling and pain, chills, and/or fever. If left untreated, destructive changes may develop in the joints.Familial apatite crystal deposition disease is a rare inherited metabolic disorder characterized by deposits of carbonate-substituted calcium hydroxyapatite in the joints. Symptoms may include morning stiffness, pain, and limited mobility due to crystal accumulation in the joints and spine. Pain may also occur in the area of the ribs (costochondral) and in the small joints of the hands. Familial apatite crystal deposition disease is inherited as an autosomal dominant genetic trait.Chondrocalcinosis 1 is a genetic type of CPPD caused by mutations in a gene on chromosome 8. This condition was reported in one 6-generation family and appears to follow autosomal dominant inheritance. Affected family members had early onset osteoarthritis and chondrocalcinosis. | Related disorders of Chondrocalcinosis 2. Symptoms of the following disorders can be similar to those of CCAL2. Comparisons may be useful for a differential diagnosis:Sporadic CPDD typically occurs in people over age 60, but causes similar symptoms of acute and chronic arthritis. The non-genetic forms may also occur in association with certain metabolic conditions such as hyperparathyroidism, familial hypocalciuric hypercalcemia, Wilson’s disease, Bartter’s syndrome, hypophosphatasia, hypomagnesemia, and hereditary hemochromatosis. Gout is a common metabolic disorder characterized by an inborn error of uric acid (purine) metabolism. Excessive uric acid may form crystals composed of monosodium urate, that are deposited in the joints, and other areas of the body. The large toe is the most common site for the accumulation of crystals. Symptoms may include sharp pain in the toe or other affected area, joint swelling and pain, chills, and/or fever. If left untreated, destructive changes may develop in the joints.Familial apatite crystal deposition disease is a rare inherited metabolic disorder characterized by deposits of carbonate-substituted calcium hydroxyapatite in the joints. Symptoms may include morning stiffness, pain, and limited mobility due to crystal accumulation in the joints and spine. Pain may also occur in the area of the ribs (costochondral) and in the small joints of the hands. Familial apatite crystal deposition disease is inherited as an autosomal dominant genetic trait.Chondrocalcinosis 1 is a genetic type of CPPD caused by mutations in a gene on chromosome 8. This condition was reported in one 6-generation family and appears to follow autosomal dominant inheritance. Affected family members had early onset osteoarthritis and chondrocalcinosis. | 233 | Chondrocalcinosis 2 |
nord_233_5 | Diagnosis of Chondrocalcinosis 2 | Few or no symptoms may be apparent in the first several decades of life. X-rays of joints, especially the knees and wrists, may detect calcifications before symptoms occur. The diagnosis of CCAL2 is based on a clinical evaluation that includes a thorough patient history and specialized laboratory tests. In one test, fluid is removed from an affected joint (synovial fluid). The presence of calcium pyrophosphate crystals in this fluid confirms the diagnosis of articular chondrocalcinosis. Radiographic (x-ray) studies typically demonstrate calcium pyrophosphate deposits in the cartilage in joints (articular).Joint ultrasonography is well tolerated by patients, and is another method of observing calcified deposits in soft tissues.Molecular genetic testing for mutations in the ANKH gene is available to confirm the diagnosis. | Diagnosis of Chondrocalcinosis 2. Few or no symptoms may be apparent in the first several decades of life. X-rays of joints, especially the knees and wrists, may detect calcifications before symptoms occur. The diagnosis of CCAL2 is based on a clinical evaluation that includes a thorough patient history and specialized laboratory tests. In one test, fluid is removed from an affected joint (synovial fluid). The presence of calcium pyrophosphate crystals in this fluid confirms the diagnosis of articular chondrocalcinosis. Radiographic (x-ray) studies typically demonstrate calcium pyrophosphate deposits in the cartilage in joints (articular).Joint ultrasonography is well tolerated by patients, and is another method of observing calcified deposits in soft tissues.Molecular genetic testing for mutations in the ANKH gene is available to confirm the diagnosis. | 233 | Chondrocalcinosis 2 |
nord_233_6 | Therapies of Chondrocalcinosis 2 | Treatment
Treatment for CCAL2 is symptomatic. There is no way to prevent the formation of calcium pyrophosphate crystals or to satisfactorily remove existing crystals from the joints. Acute attacks of CCAL2 are treated in several ways. Excess fluid may be drained from the affected joint using a needle and syringe. If only one joint is involved, a corticosteroid drug may be injected directly into the affected joint (intra-articular). For those individuals with frequent, recurring acute attacks, colchicine or oral corticosteroids, such as prednisone, may be effective. These medications are also used to treat gout. Other drugs that are frequently used include nonsteroidal anti-inflammatory drugs (e.g., ibuprofen and naproxen sodium) which are commonly prescribed for many types of arthritic conditions. When corticosteroids, nonsteroidal anti-inflammatory drugs, and colchicine are ineffective, contraindicated, or not well-tolerated, drugs that inhibit the cytokine interleukin 1 alpha might be helpful. There is some evidence that methotrexate and hydroxychloroquine may also be useful, but the effectiveness of these drugs is not well studied.During an acute attack of arthritis, the affected joint may require rest. Splints, canes, and other devices that protect and support the joint may be prescribed and may require special fitting. Once the episode subsides, rest should be balanced with appropriate exercise that is carefully monitored by a physician or physical therapist.In some people with CCAL2, surgery may be necessary to repair a joint that is badly damaged. Surgery may be an effective means for reducing pain and enhancing mobility in some people.Asymptomatic CCAL2 does not require treatment.Genetic counseling may be of benefit for affected individuals and their families. | Therapies of Chondrocalcinosis 2. Treatment
Treatment for CCAL2 is symptomatic. There is no way to prevent the formation of calcium pyrophosphate crystals or to satisfactorily remove existing crystals from the joints. Acute attacks of CCAL2 are treated in several ways. Excess fluid may be drained from the affected joint using a needle and syringe. If only one joint is involved, a corticosteroid drug may be injected directly into the affected joint (intra-articular). For those individuals with frequent, recurring acute attacks, colchicine or oral corticosteroids, such as prednisone, may be effective. These medications are also used to treat gout. Other drugs that are frequently used include nonsteroidal anti-inflammatory drugs (e.g., ibuprofen and naproxen sodium) which are commonly prescribed for many types of arthritic conditions. When corticosteroids, nonsteroidal anti-inflammatory drugs, and colchicine are ineffective, contraindicated, or not well-tolerated, drugs that inhibit the cytokine interleukin 1 alpha might be helpful. There is some evidence that methotrexate and hydroxychloroquine may also be useful, but the effectiveness of these drugs is not well studied.During an acute attack of arthritis, the affected joint may require rest. Splints, canes, and other devices that protect and support the joint may be prescribed and may require special fitting. Once the episode subsides, rest should be balanced with appropriate exercise that is carefully monitored by a physician or physical therapist.In some people with CCAL2, surgery may be necessary to repair a joint that is badly damaged. Surgery may be an effective means for reducing pain and enhancing mobility in some people.Asymptomatic CCAL2 does not require treatment.Genetic counseling may be of benefit for affected individuals and their families. | 233 | Chondrocalcinosis 2 |
nord_234_0 | Overview of Chordoma | SummaryA chordoma is a rare tumor that develops in the bones of the skull and the spine. These tumors arise from the remnants of the notochord, a flexible, rod-like structure that provides support to the developing embryo. During fetal development, the notochord is replaced by the bones of the spine. Notochordal cells that persist within the spinal column may give rise to chordoma. Chordomas are slow growing tumors that cause destruction of the surrounding bone and eventually extend into the surrounding soft tissue. Sometimes chordoma spreads through the bloodstream (metastasizes) to other organs, such as the lungs, lymph nodes, liver or other bones. Although chordoma can develop at any point during life, it most commonly occurs in older adults. The symptoms associated with a chordoma depend upon the size and location of the tumor. Almost all cases of chordoma occur randomly for no apparent reason. In extremely rare cases, chordomas may develop in multiple members of the same family as a result of certain genetic risk factors (familial chordoma).IntroductionChordomas may be classified as a type of sarcoma. Sarcoma is a general term for a group of cancers that can affect bone or connective tissue – the tissues that connect, support and surround various structures and organs in the body. Although chordomas are primary bone tumors, they are sometimes classified as central nervous system tumors when they occur near the skull base. | Overview of Chordoma. SummaryA chordoma is a rare tumor that develops in the bones of the skull and the spine. These tumors arise from the remnants of the notochord, a flexible, rod-like structure that provides support to the developing embryo. During fetal development, the notochord is replaced by the bones of the spine. Notochordal cells that persist within the spinal column may give rise to chordoma. Chordomas are slow growing tumors that cause destruction of the surrounding bone and eventually extend into the surrounding soft tissue. Sometimes chordoma spreads through the bloodstream (metastasizes) to other organs, such as the lungs, lymph nodes, liver or other bones. Although chordoma can develop at any point during life, it most commonly occurs in older adults. The symptoms associated with a chordoma depend upon the size and location of the tumor. Almost all cases of chordoma occur randomly for no apparent reason. In extremely rare cases, chordomas may develop in multiple members of the same family as a result of certain genetic risk factors (familial chordoma).IntroductionChordomas may be classified as a type of sarcoma. Sarcoma is a general term for a group of cancers that can affect bone or connective tissue – the tissues that connect, support and surround various structures and organs in the body. Although chordomas are primary bone tumors, they are sometimes classified as central nervous system tumors when they occur near the skull base. | 234 | Chordoma |
nord_234_1 | Symptoms of Chordoma | A chordoma can develop anywhere along the spine from the base of the skull to the tailbone (coccyx). The most common locations for a chordoma are at the triangular bone near the base of the spine (sacrum), the coccyx, and the clivus, which is a bone in the base of the skull. The clivus is located in front of the brainstem and behind the back of the throat.Symptoms vary from one person to another and depend in part upon the location and size of the tumor. Chordomas located in the lower spine may be associated with lower back pain and tenderness, pain the legs, weakness and numbness in the lower back or legs, and abnormalities affecting the bladder and intestines including loss of bladder control (urinary incontinence) and/or loss of bowel control. In some cases, a mass may be felt (palpable) over the small of the back.Chordomas of the skull base (cranial chordomas) can be associated with double vision (diplopia), headaches, and/or facial pain. Paralysis (palsy) of certain facial nerves can also occur, resulting in swallowing difficulties, speech and voice abnormalities, and abnormal eye movements.In some cases, an intracranial chordoma can block the flow of cerebrospinal fluid (CSF), causing CSF to accumulate in the skull and putting pressure on the brain (hydrocephalus). Hydrocephalus can cause several symptoms that differ based upon age. In infants, it can cause bulging at the soft spots on the skull, an increase in head circumference, and downward casting of the eyes (sunsetting). In older children, it can cause nausea, vomiting, sleepiness, double vision, rapid eye movements and difficulties with balance. In adults, it can also cause headaches, changes in personality, and difficulty focusing the eyes.Chordomas in the area immediately below the skull (cervical spine) can cause neck pain, hoarseness, difficulty swallowing (dysphagia), and, less often, bleeding from the voice box (laryngeal bleeding). | Symptoms of Chordoma. A chordoma can develop anywhere along the spine from the base of the skull to the tailbone (coccyx). The most common locations for a chordoma are at the triangular bone near the base of the spine (sacrum), the coccyx, and the clivus, which is a bone in the base of the skull. The clivus is located in front of the brainstem and behind the back of the throat.Symptoms vary from one person to another and depend in part upon the location and size of the tumor. Chordomas located in the lower spine may be associated with lower back pain and tenderness, pain the legs, weakness and numbness in the lower back or legs, and abnormalities affecting the bladder and intestines including loss of bladder control (urinary incontinence) and/or loss of bowel control. In some cases, a mass may be felt (palpable) over the small of the back.Chordomas of the skull base (cranial chordomas) can be associated with double vision (diplopia), headaches, and/or facial pain. Paralysis (palsy) of certain facial nerves can also occur, resulting in swallowing difficulties, speech and voice abnormalities, and abnormal eye movements.In some cases, an intracranial chordoma can block the flow of cerebrospinal fluid (CSF), causing CSF to accumulate in the skull and putting pressure on the brain (hydrocephalus). Hydrocephalus can cause several symptoms that differ based upon age. In infants, it can cause bulging at the soft spots on the skull, an increase in head circumference, and downward casting of the eyes (sunsetting). In older children, it can cause nausea, vomiting, sleepiness, double vision, rapid eye movements and difficulties with balance. In adults, it can also cause headaches, changes in personality, and difficulty focusing the eyes.Chordomas in the area immediately below the skull (cervical spine) can cause neck pain, hoarseness, difficulty swallowing (dysphagia), and, less often, bleeding from the voice box (laryngeal bleeding). | 234 | Chordoma |
nord_234_2 | Causes of Chordoma | The underlying causes of chordoma are unknown. Most cases arise spontaneously and are not due to an inherited genetic change. A prevailing theory is that acquired genetic abnormalities or mutations result in cancerous growth of notochordal remnants. These genetic abnormalities may arise spontaneously for unknown reasons or, more rarely, be inherited.Both non-familial and familial chordomas have been linked to the T gene located on the long arm of chromosome 6 (6q27). This gene creates (encodes) a protein known as transcription factor T or brachyury homologue. This protein is important in the development of the notochord and is highly expressed in the chordoma cells.Most individuals with a sporadic chordoma have a single nucleotide polymorphism (SNP) in the T gene. SNPs are the most common genetic variation in humans and occur frequently in a person’s DNA. Most SNPs have no effect on a person’s health. The SNP in the T gene has been identified in over 80% patients with sporadic chordoma (compared to around 50% of people without chordoma), and therefore is believed to convey a predisposition to developing chordoma. However, since this SNP is common in the general population and most people who have it do not develop chordoma additional factors are thought to be necessary for the development of chordoma.Researchers have also learned that many familial chordomas are due to a specific chromosomal abnormality known as a duplication, in which three copies of the T gene are present instead of two. This extra copy of the T gene seems to be associated with a strong genetic predisposition to developing a chordoma.Abnormalities on chromosome 7 have been studied as potential cause of familial and non-familial chordoma. Multiple additional complex chromosomal abnormalities (involving chromosomes 1p, 3, 4, 9p, 9q, 10, and 13) have been identified in some tumors as well. Whether these various abnormalities play a role in the development of a chordoma in specific cases is unknown. Further research is necessary to determine the complex mechanisms responsible for the development of a chordoma. | Causes of Chordoma. The underlying causes of chordoma are unknown. Most cases arise spontaneously and are not due to an inherited genetic change. A prevailing theory is that acquired genetic abnormalities or mutations result in cancerous growth of notochordal remnants. These genetic abnormalities may arise spontaneously for unknown reasons or, more rarely, be inherited.Both non-familial and familial chordomas have been linked to the T gene located on the long arm of chromosome 6 (6q27). This gene creates (encodes) a protein known as transcription factor T or brachyury homologue. This protein is important in the development of the notochord and is highly expressed in the chordoma cells.Most individuals with a sporadic chordoma have a single nucleotide polymorphism (SNP) in the T gene. SNPs are the most common genetic variation in humans and occur frequently in a person’s DNA. Most SNPs have no effect on a person’s health. The SNP in the T gene has been identified in over 80% patients with sporadic chordoma (compared to around 50% of people without chordoma), and therefore is believed to convey a predisposition to developing chordoma. However, since this SNP is common in the general population and most people who have it do not develop chordoma additional factors are thought to be necessary for the development of chordoma.Researchers have also learned that many familial chordomas are due to a specific chromosomal abnormality known as a duplication, in which three copies of the T gene are present instead of two. This extra copy of the T gene seems to be associated with a strong genetic predisposition to developing a chordoma.Abnormalities on chromosome 7 have been studied as potential cause of familial and non-familial chordoma. Multiple additional complex chromosomal abnormalities (involving chromosomes 1p, 3, 4, 9p, 9q, 10, and 13) have been identified in some tumors as well. Whether these various abnormalities play a role in the development of a chordoma in specific cases is unknown. Further research is necessary to determine the complex mechanisms responsible for the development of a chordoma. | 234 | Chordoma |
nord_234_3 | Affects of Chordoma | Chordomas can affect individuals of any age, including young children, but most often are diagnosed in individuals between 40-75 years of age (the average age at diagnosis is 55 years). Collectively, chordomas affect males more often than females by a ratio of approximately 2:1. However, skull base tumors have an equal (1:1) gender distribution. Children are more likely to have skull base tumors. Chordomas account for approximately 1-4% of all malignant bone tumors and around 20% of primary tumors of the spinal column. The incidence of chordoma is estimated to be approximately 1 per 1,000,000 people. About 300 new cases of chordoma are diagnosed in the United States each year. Some reports state that these tumors are more common in individuals of European ancestry. | Affects of Chordoma. Chordomas can affect individuals of any age, including young children, but most often are diagnosed in individuals between 40-75 years of age (the average age at diagnosis is 55 years). Collectively, chordomas affect males more often than females by a ratio of approximately 2:1. However, skull base tumors have an equal (1:1) gender distribution. Children are more likely to have skull base tumors. Chordomas account for approximately 1-4% of all malignant bone tumors and around 20% of primary tumors of the spinal column. The incidence of chordoma is estimated to be approximately 1 per 1,000,000 people. About 300 new cases of chordoma are diagnosed in the United States each year. Some reports state that these tumors are more common in individuals of European ancestry. | 234 | Chordoma |
nord_234_4 | Related disorders of Chordoma | Chondrosarcoma is a general term for a type of bone cancer that arises from cartilage cells. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted into bone. Chondrosarcomas typically affect the arms, legs, and pelvis, but can affect any area that contains cartilage including the skull base and spinal column. Most cases are diagnosed in adults between the ages of 20 and 60. Chondrosarcomas are malignant and may spread to other areas of the body. (For more information on this disorder, choose “chondrosarcoma” as your search term in the Rare Disease Database.) | Related disorders of Chordoma. Chondrosarcoma is a general term for a type of bone cancer that arises from cartilage cells. Cartilage is the specialized tissue that serves as a buffer or cushion at joints. Most of the skeleton of an embryo consists of cartilage, which is slowly converted into bone. Chondrosarcomas typically affect the arms, legs, and pelvis, but can affect any area that contains cartilage including the skull base and spinal column. Most cases are diagnosed in adults between the ages of 20 and 60. Chondrosarcomas are malignant and may spread to other areas of the body. (For more information on this disorder, choose “chondrosarcoma” as your search term in the Rare Disease Database.) | 234 | Chordoma |
nord_234_5 | Diagnosis of Chordoma | The symptoms of chordoma are not specific. Therefore the diagnosis is based on characteristic radiologic pathologic findings.Clinical Testing and Workup
Plain x-rays (radiography) or other specialized imaging techniques may be used to diagnose a chordoma. Such specialized imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer uses x-rays to create cross-sectional images of the body. An MRI uses magnetic fields and radio waves to produce cross-sectional images. These imaging techniques may be used to detect the presence of a tumor and can evaluate the size, location, and local extension of the tumor, which help surgeons plan any surgical procedures that may be indicated for treatment.A core needle or incisional biopsy is necessary to confirm a diagnosis of chordoma. During this procedure, a physician inserts a needle through the skin and into the tumor to obtain a small sample of cells. In some cases, a surgical procedure is necessary to procure enough tissue for diagnosis. A pathologist examines the tissue sample under a microscope to determine the specific type of tumor present. | Diagnosis of Chordoma. The symptoms of chordoma are not specific. Therefore the diagnosis is based on characteristic radiologic pathologic findings.Clinical Testing and Workup
Plain x-rays (radiography) or other specialized imaging techniques may be used to diagnose a chordoma. Such specialized imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer uses x-rays to create cross-sectional images of the body. An MRI uses magnetic fields and radio waves to produce cross-sectional images. These imaging techniques may be used to detect the presence of a tumor and can evaluate the size, location, and local extension of the tumor, which help surgeons plan any surgical procedures that may be indicated for treatment.A core needle or incisional biopsy is necessary to confirm a diagnosis of chordoma. During this procedure, a physician inserts a needle through the skin and into the tumor to obtain a small sample of cells. In some cases, a surgical procedure is necessary to procure enough tissue for diagnosis. A pathologist examines the tissue sample under a microscope to determine the specific type of tumor present. | 234 | Chordoma |
nord_234_6 | Therapies of Chordoma | TreatmentTreatment usually requires the coordinated effort of a team of specialists. Physicians who specialize in the diagnosing and treatment of cancer (oncologists), physicians who specialize in using ionizing radiation to treat cancer (radiation oncologists), neurosurgeons, physicians who specialize in the diagnosis and treatment of the musculoskeletal system (orthopedic surgeons), and other healthcare professionals need to systematically and comprehensively plan an affected person’s treatment.Specific therapeutic procedures and interventions may vary depending upon numerous factors such as disease stage, tumor size and location, specific tumor subtype, the presence or absence of certain symptoms, and the age and general physical health of the patient. 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 together with the patient. Thorough discussions of the potential benefits and risks of specific therapies, including possible side effects are helpful in allowing the patient to make an informed decision regarding his or her preferred therapy.Treatment for chordoma usually involves surgery to remove as much as the tumor as possible while preserving neurological function and quality of life. Because these tumors are located near the brain or in the spinal cord, surgical removal may be difficult and the surgeon may not be able to remove the entire tumor despite multiple operations. Removing the entire tumor through surgery in one piece (total en bloc resection) is possible for only approximately 50% of sacral chordomas. The percentage is even lower in chordomas of the spine and skull base. Clival chordomas can rarely be removed through en bloc resection, and often require other advanced neurosurgical techniques.Radiation therapy is often used in conjunction with surgery to treat a chordoma and lower the risk of recurrence. Unfortunately, chordomas are generally resistant to radiation therapy and high doses of radiation are often necessary.A chordoma may recur despite successful treatment with surgery and radiation. Recurrence is common and may require additional surgical and/or radiation therapy.Referral to a specialized cancer center with physicians who have experience in diagnosing, treating, and managing chordoma patients is strongly recommended. | Therapies of Chordoma. TreatmentTreatment usually requires the coordinated effort of a team of specialists. Physicians who specialize in the diagnosing and treatment of cancer (oncologists), physicians who specialize in using ionizing radiation to treat cancer (radiation oncologists), neurosurgeons, physicians who specialize in the diagnosis and treatment of the musculoskeletal system (orthopedic surgeons), and other healthcare professionals need to systematically and comprehensively plan an affected person’s treatment.Specific therapeutic procedures and interventions may vary depending upon numerous factors such as disease stage, tumor size and location, specific tumor subtype, the presence or absence of certain symptoms, and the age and general physical health of the patient. 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 together with the patient. Thorough discussions of the potential benefits and risks of specific therapies, including possible side effects are helpful in allowing the patient to make an informed decision regarding his or her preferred therapy.Treatment for chordoma usually involves surgery to remove as much as the tumor as possible while preserving neurological function and quality of life. Because these tumors are located near the brain or in the spinal cord, surgical removal may be difficult and the surgeon may not be able to remove the entire tumor despite multiple operations. Removing the entire tumor through surgery in one piece (total en bloc resection) is possible for only approximately 50% of sacral chordomas. The percentage is even lower in chordomas of the spine and skull base. Clival chordomas can rarely be removed through en bloc resection, and often require other advanced neurosurgical techniques.Radiation therapy is often used in conjunction with surgery to treat a chordoma and lower the risk of recurrence. Unfortunately, chordomas are generally resistant to radiation therapy and high doses of radiation are often necessary.A chordoma may recur despite successful treatment with surgery and radiation. Recurrence is common and may require additional surgical and/or radiation therapy.Referral to a specialized cancer center with physicians who have experience in diagnosing, treating, and managing chordoma patients is strongly recommended. | 234 | Chordoma |
nord_235_0 | Overview of Choroideremia | Choroideremia is a genetic disorder of sight that usually affects males. Female carriers may have mild symptoms without loss of vision. Major symptoms are difficulty seeing in the dark leading to progressive loss of peripheral vision, followed by tunnel vision. The rate and degree of vision loss differs among individuals. Night blindness, usually the first noticeable symptom, generally occurs during childhood. | Overview of Choroideremia. Choroideremia is a genetic disorder of sight that usually affects males. Female carriers may have mild symptoms without loss of vision. Major symptoms are difficulty seeing in the dark leading to progressive loss of peripheral vision, followed by tunnel vision. The rate and degree of vision loss differs among individuals. Night blindness, usually the first noticeable symptom, generally occurs during childhood. | 235 | Choroideremia |
nord_235_1 | Symptoms of Choroideremia | Choroideremia is characterized by extensive loss of all retinal layers in the eyes. This disorder usually begins during childhood with wasting (atrophy) of the pigmented retinal epithelium, retina, and choroid. The retina is the light sensitive, most internal layer, consisting of many nerve containing layers. A layer of single pigmented cells is the layer outside of the retina. The choroid is the next layer located between the retina and the “white” section of the eye (the sclera); this layer contains small blood vessel).Degeneration of the blood vessels of the choroid is followed by damage to the retina, which usually leads to loss of peripheral vision that can progress to eventual blindness. Central vision is usually preserved until late in life. The symptoms of choroideremia may vary greatly between affected individuals. Female carriers usually have very mild symptoms with night blindness or sensitivity to glare occurring late in life. | Symptoms of Choroideremia. Choroideremia is characterized by extensive loss of all retinal layers in the eyes. This disorder usually begins during childhood with wasting (atrophy) of the pigmented retinal epithelium, retina, and choroid. The retina is the light sensitive, most internal layer, consisting of many nerve containing layers. A layer of single pigmented cells is the layer outside of the retina. The choroid is the next layer located between the retina and the “white” section of the eye (the sclera); this layer contains small blood vessel).Degeneration of the blood vessels of the choroid is followed by damage to the retina, which usually leads to loss of peripheral vision that can progress to eventual blindness. Central vision is usually preserved until late in life. The symptoms of choroideremia may vary greatly between affected individuals. Female carriers usually have very mild symptoms with night blindness or sensitivity to glare occurring late in life. | 235 | Choroideremia |
nord_235_2 | Causes of Choroideremia | Choroideremia can be caused by many different changes (called variants or mutations) in the CHM gene. The CHM gene encodes REP1 (RAB escort protein 1), a protein that takes part in targeting vesicles (small sacs of substances) into, out of and within cells.Choroideremia is an X linked recessive genetic condition. These disorders are caused by an abnormal gene on the X chromosome and manifest mostly in males. Females who have an altered gene on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms, because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mothers; if a male inherits an X chromosome that contains the altered gene, he will develop the disease.Female carriers of an X linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.If a male with an X linked disorder has a child, he will pass the altered gene to all of his daughters, who will be carriers. A male cannot pass an X linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. | Causes of Choroideremia. Choroideremia can be caused by many different changes (called variants or mutations) in the CHM gene. The CHM gene encodes REP1 (RAB escort protein 1), a protein that takes part in targeting vesicles (small sacs of substances) into, out of and within cells.Choroideremia is an X linked recessive genetic condition. These disorders are caused by an abnormal gene on the X chromosome and manifest mostly in males. Females who have an altered gene on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms, because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mothers; if a male inherits an X chromosome that contains the altered gene, he will develop the disease.Female carriers of an X linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.If a male with an X linked disorder has a child, he will pass the altered gene to all of his daughters, who will be carriers. A male cannot pass an X linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. | 235 | Choroideremia |
nord_235_3 | Affects of Choroideremia | Choroideremia affects primarily males. Female carriers generally have few or no symptoms. However, a small number of females develop the disorder because of a genetic process that inactivates the normal gene and leaves only the dysfunctional gene active. In the Salla area of northern Finland, an unusually high number of people have been diagnosed with choroideremia; approximately one in forty persons. | Affects of Choroideremia. Choroideremia affects primarily males. Female carriers generally have few or no symptoms. However, a small number of females develop the disorder because of a genetic process that inactivates the normal gene and leaves only the dysfunctional gene active. In the Salla area of northern Finland, an unusually high number of people have been diagnosed with choroideremia; approximately one in forty persons. | 235 | Choroideremia |
nord_235_4 | Related disorders of Choroideremia | Symptoms of the following disorders can be similar to those of choroideremia. Comparisons may be useful for differential diagnosis:X linked retinitis pigmentosa (RP) is the most common inherited vision disorder that has similar symptoms to choroideremia. X linked RP is passed from a mother (who carries or has RP) to a son. In RP, the retina degenerates, vision decreases and can be lost. Symptoms include night blindness leading to progressive loss of peripheral vision, followed by tunnel vision. Night blindness is usually the first noticeable symptom, generally occurring during childhood. This is followed by tunnel vision (loss of peripheral vision). The extent and progression of symptoms is variable. An eye doctor (ophthalmologist) can differentiate between RP and choroideremia with an eye exam. (For more information on this disorder, choose “retinitis pigmentosa” as your search term in the Rare Disease Database.)Gyrate atrophy of the choroid and retina is characterized by a circular degeneration in the choroid and retina of the eye. Because this eye disorder results from the accumulation of ornithine in the blood, a blood test can be used to help diagnose it. In general, patients with this eye condition as have other medical problems such as muscle weakness.Very rarely, a single genetic variant in the RPE65 gene (D447G) can cause a dominantly inherited condition that affects the retinal pigment epithelium and looks like choroideremia. The key feature is the pattern of inheritance is not X-linked. | Related disorders of Choroideremia. Symptoms of the following disorders can be similar to those of choroideremia. Comparisons may be useful for differential diagnosis:X linked retinitis pigmentosa (RP) is the most common inherited vision disorder that has similar symptoms to choroideremia. X linked RP is passed from a mother (who carries or has RP) to a son. In RP, the retina degenerates, vision decreases and can be lost. Symptoms include night blindness leading to progressive loss of peripheral vision, followed by tunnel vision. Night blindness is usually the first noticeable symptom, generally occurring during childhood. This is followed by tunnel vision (loss of peripheral vision). The extent and progression of symptoms is variable. An eye doctor (ophthalmologist) can differentiate between RP and choroideremia with an eye exam. (For more information on this disorder, choose “retinitis pigmentosa” as your search term in the Rare Disease Database.)Gyrate atrophy of the choroid and retina is characterized by a circular degeneration in the choroid and retina of the eye. Because this eye disorder results from the accumulation of ornithine in the blood, a blood test can be used to help diagnose it. In general, patients with this eye condition as have other medical problems such as muscle weakness.Very rarely, a single genetic variant in the RPE65 gene (D447G) can cause a dominantly inherited condition that affects the retinal pigment epithelium and looks like choroideremia. The key feature is the pattern of inheritance is not X-linked. | 235 | Choroideremia |
nord_235_5 | Diagnosis of Choroideremia | A doctor will perform tests that examine the patient’s visual field suspected of having choroideremia and will look inside the eye for degeneration of the retina. Genetic testing is available for some genetic variants that cause choroideremia. | Diagnosis of Choroideremia. A doctor will perform tests that examine the patient’s visual field suspected of having choroideremia and will look inside the eye for degeneration of the retina. Genetic testing is available for some genetic variants that cause choroideremia. | 235 | Choroideremia |
nord_235_6 | Therapies of Choroideremia | The symptoms of choroideremia can be treated but the disease itself cannot yet be cured. Organizations providing services to sight impaired people help patients and their families. Genetic counseling is recommended for families affected by this disorder. | Therapies of Choroideremia. The symptoms of choroideremia can be treated but the disease itself cannot yet be cured. Organizations providing services to sight impaired people help patients and their families. Genetic counseling is recommended for families affected by this disorder. | 235 | Choroideremia |
nord_236_0 | Overview of Choroiditis, Serpiginous | Serpiginous Choroiditis is one of the conditions in a group termed the white dot syndromes which all involve inflammation of the retina and choroid and are defined by the appearance of white dots in the posterior inner part of the eye (fundus). Serpiginous Choroiditis is a rare recurrent eye disorder characterized by irregularly shaped (serpiginous) lesions involving two layers of the eye surface (the retinal pigment epithelium and the choriocapillaris). No symptoms are apparent unless a specific area of the retina (macula) is damaged. A sudden, painless decrease in vision in one or both eyes may be the first sign of Serpiginous Choroiditis. Patients may also notice blind gaps in the visual field (scotomata) or a sensation of flashes of light (photopsia). Both eyes are commonly affected, although the second eye may not develop lesions for weeks to years after the first eye. The exact cause of Serpiginous Choroiditis is not known. | Overview of Choroiditis, Serpiginous. Serpiginous Choroiditis is one of the conditions in a group termed the white dot syndromes which all involve inflammation of the retina and choroid and are defined by the appearance of white dots in the posterior inner part of the eye (fundus). Serpiginous Choroiditis is a rare recurrent eye disorder characterized by irregularly shaped (serpiginous) lesions involving two layers of the eye surface (the retinal pigment epithelium and the choriocapillaris). No symptoms are apparent unless a specific area of the retina (macula) is damaged. A sudden, painless decrease in vision in one or both eyes may be the first sign of Serpiginous Choroiditis. Patients may also notice blind gaps in the visual field (scotomata) or a sensation of flashes of light (photopsia). Both eyes are commonly affected, although the second eye may not develop lesions for weeks to years after the first eye. The exact cause of Serpiginous Choroiditis is not known. | 236 | Choroiditis, Serpiginous |
nord_236_1 | Symptoms of Choroiditis, Serpiginous | Serpiginous Choroiditis is a rare disorder characterized by recurrent lesions affecting two layers of the eye (the retinal pigment epithelium and the choriocapillaris). The retina is the light-sensitive internal coat of the eyeball, consisting of eight layers. Seven of these layers contain nerves, and one layer contains pigmentation (retinal pigment epithelium). The choroid is a vascular membrane located between the retina inside the eye and the “white” section on the outside of the eye (sclera). The choriocapillaris is the layer of the choroid next to the retina.Lesions usually begin at the back of the eye near the connection to the optic nerve (optic disk) and may then extend in any direction along the eye layers. Lesions may also begin at other locations and spread toward the optic disk. The disorder has two stages: an acute stage during which lesions develop and/or spread, and a chronic stage during which the disease does not progress but inactive lesions lead to scarring, wasting of tissue (atrophy), and/or clumping of pigment. Recurrences usually start in scar tissue left by old lesions.Symptoms of Serpiginous Choroiditis appear only if a specific area of the retina (macula) is damaged. A sudden, painless decrease in central vision in one eye may be the first noticeable sign of disease. Blurred central vision and/or the sensation that something is obstructing central vision (positive scotoma) are characteristic symptoms. Both eyes are commonly affected, although the second eye may not develop lesions for weeks to years after the first eye. Vision outside center vision (peripheral) remains normal in most cases. Recurrences are common for this condition.A membrane composed of tiny fibers and blood vessels (subretinal neovascular membrane) may grow from the choriocapillaris and cause vision distortion and/or blurring in some people with Serpiginous Choroiditis. If a neovascular membrane affects the macular region of the retina, central vision loss may occur. | Symptoms of Choroiditis, Serpiginous. Serpiginous Choroiditis is a rare disorder characterized by recurrent lesions affecting two layers of the eye (the retinal pigment epithelium and the choriocapillaris). The retina is the light-sensitive internal coat of the eyeball, consisting of eight layers. Seven of these layers contain nerves, and one layer contains pigmentation (retinal pigment epithelium). The choroid is a vascular membrane located between the retina inside the eye and the “white” section on the outside of the eye (sclera). The choriocapillaris is the layer of the choroid next to the retina.Lesions usually begin at the back of the eye near the connection to the optic nerve (optic disk) and may then extend in any direction along the eye layers. Lesions may also begin at other locations and spread toward the optic disk. The disorder has two stages: an acute stage during which lesions develop and/or spread, and a chronic stage during which the disease does not progress but inactive lesions lead to scarring, wasting of tissue (atrophy), and/or clumping of pigment. Recurrences usually start in scar tissue left by old lesions.Symptoms of Serpiginous Choroiditis appear only if a specific area of the retina (macula) is damaged. A sudden, painless decrease in central vision in one eye may be the first noticeable sign of disease. Blurred central vision and/or the sensation that something is obstructing central vision (positive scotoma) are characteristic symptoms. Both eyes are commonly affected, although the second eye may not develop lesions for weeks to years after the first eye. Vision outside center vision (peripheral) remains normal in most cases. Recurrences are common for this condition.A membrane composed of tiny fibers and blood vessels (subretinal neovascular membrane) may grow from the choriocapillaris and cause vision distortion and/or blurring in some people with Serpiginous Choroiditis. If a neovascular membrane affects the macular region of the retina, central vision loss may occur. | 236 | Choroiditis, Serpiginous |
nord_236_2 | Causes of Choroiditis, Serpiginous | The exact cause of Serpiginous Choroiditis is not known. Symptoms develop due to lesions that damage the part of the retina that absorbs short wavelengths of light (macular region). Vision loss may also occur if a membrane composed of fibers and blood vessels (subretinal neovascular membrane) develops and then moves into the macular region. It has been suggested in the medical literature that an abnormal immune response may cause inflammation of the blood vessels (localized vasculitis) of the eye, leading to the development of Serpiginous Choroiditis. Some scientists suggest that the disorder is one of impaired blood circulation in the eye membranes. A few affected individuals have been reported to have had chronic exposure to an unusual variety of chemicals, but the relationship between this exposure and the development of Serpiginous Choroiditis is not clear at this time. | Causes of Choroiditis, Serpiginous. The exact cause of Serpiginous Choroiditis is not known. Symptoms develop due to lesions that damage the part of the retina that absorbs short wavelengths of light (macular region). Vision loss may also occur if a membrane composed of fibers and blood vessels (subretinal neovascular membrane) develops and then moves into the macular region. It has been suggested in the medical literature that an abnormal immune response may cause inflammation of the blood vessels (localized vasculitis) of the eye, leading to the development of Serpiginous Choroiditis. Some scientists suggest that the disorder is one of impaired blood circulation in the eye membranes. A few affected individuals have been reported to have had chronic exposure to an unusual variety of chemicals, but the relationship between this exposure and the development of Serpiginous Choroiditis is not clear at this time. | 236 | Choroiditis, Serpiginous |
nord_236_3 | Affects of Choroiditis, Serpiginous | Serpiginous Choroiditis is a rare disorder that affects males more often than females. Symptoms usually appear during the early to middle adult years. | Affects of Choroiditis, Serpiginous. Serpiginous Choroiditis is a rare disorder that affects males more often than females. Symptoms usually appear during the early to middle adult years. | 236 | Choroiditis, Serpiginous |
nord_236_4 | Related disorders of Choroiditis, Serpiginous | Symptoms of the following disorders can be similar to those of Serpiginous Choroiditis. Comparisons may be useful for a differential diagnosis:Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is a rare acquired eye disorder characterized by the sudden onset of vision loss and inflammation of the outer retina and the pigmented layer of the retina (retinal pigment epithelium). Multiple yellow-white plaque-like lesions appear in the posterior pole of the retina in each eye. The rapid but temporary vision loss often subsides without treatment. Pigment alterations usually remain after resolution of the lesions. Vision loss may be permanent if the lesions affect a specific area on the retina (subfoveally), but more than 90 percent of affected individuals recover visual clarity within a few months of onset. (For more information on this disorder, choose “APMPPE” as your search term in the Rare Disease Database.)Posterior Uveitis is an eye disorder characterized by inflammation of the vascular layer of the eye (the uvea, which includes the iris, ciliary body and choroid). The other layers of the eye (sclera, cornea, and retina) may also be affected. Posterior Uveitis affects the rear hemisphere of the eye, while Anterior and Intermediate Uveitis affect areas of the front hemisphere. Scars left by Posterior Uveitis on the eye membranes may cause impaired vision. Major symptoms include blurred vision, distortion of the size or shape of objects (metamorphopsia), and floating black spots in the visual field. If the foveal area is affected central vision loss may occur. Onset may be sudden or gradual, depending on the cause of the disorder. In many cases, this disorder occurs as a complication of Toxoplasmosis or other infections. In other cases, the cause cannot be determined. (For more information on this disorder, choose “Posterior Uveitis” as your search term in the Rare Disease Database.)Tuberculous Uveitis is a very rare type of inflammation of the vascular layer of the eye (uveitis), and may be very difficult to differentiate from other types of uveitis. The vascular layer (uvea) includes the iris, ciliary body and choroid. Tuberculous Uveitis is characterized by a long chronic course and involvement of the choroid and the retina of the eye. Symptoms may appear suddenly, and may include blurred vision, distortion of the size or shape of objects, floating black spots in the visual field, and/or impaired central vision. Diagnosis may be made by indirect evidence, which may include a lack of response to steroid therapy, positive test results for tuberculosis, and/or the ruling out of other causes for the uveitis. In some cases, tentative therapy for tuberculosis (i.e., the antimycobacterial drug isoniazid) may be administered to determine if the uveitis responds. If the treatment is effective Tuberculous Uveitis is the probable diagnosis.Macular Degeneration is the descriptive term for many forms of deterioration of the central area of vision (macula) from a previous state of normality. There are genetic, age-related, and environmental (including toxic) causes. Subtypes of the disorder include Stargardt's Disease and fundus flavimaculatus (occuring in children), and disciform macular degeneration (termed senile macular degeneration). Macular Degeneration caused by environmental elements may occur at any age. Major symptoms may include impaired or absent central vision with normal peripheral vision, a disturbance of vision in which shapes are distorted (metamorphopsia), and/or impaired central vision (central scotoma). (For more information on this disorder, choose “Macular Degeneration” as your search term in the Rare Disease Database.) | Related disorders of Choroiditis, Serpiginous. Symptoms of the following disorders can be similar to those of Serpiginous Choroiditis. Comparisons may be useful for a differential diagnosis:Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) is a rare acquired eye disorder characterized by the sudden onset of vision loss and inflammation of the outer retina and the pigmented layer of the retina (retinal pigment epithelium). Multiple yellow-white plaque-like lesions appear in the posterior pole of the retina in each eye. The rapid but temporary vision loss often subsides without treatment. Pigment alterations usually remain after resolution of the lesions. Vision loss may be permanent if the lesions affect a specific area on the retina (subfoveally), but more than 90 percent of affected individuals recover visual clarity within a few months of onset. (For more information on this disorder, choose “APMPPE” as your search term in the Rare Disease Database.)Posterior Uveitis is an eye disorder characterized by inflammation of the vascular layer of the eye (the uvea, which includes the iris, ciliary body and choroid). The other layers of the eye (sclera, cornea, and retina) may also be affected. Posterior Uveitis affects the rear hemisphere of the eye, while Anterior and Intermediate Uveitis affect areas of the front hemisphere. Scars left by Posterior Uveitis on the eye membranes may cause impaired vision. Major symptoms include blurred vision, distortion of the size or shape of objects (metamorphopsia), and floating black spots in the visual field. If the foveal area is affected central vision loss may occur. Onset may be sudden or gradual, depending on the cause of the disorder. In many cases, this disorder occurs as a complication of Toxoplasmosis or other infections. In other cases, the cause cannot be determined. (For more information on this disorder, choose “Posterior Uveitis” as your search term in the Rare Disease Database.)Tuberculous Uveitis is a very rare type of inflammation of the vascular layer of the eye (uveitis), and may be very difficult to differentiate from other types of uveitis. The vascular layer (uvea) includes the iris, ciliary body and choroid. Tuberculous Uveitis is characterized by a long chronic course and involvement of the choroid and the retina of the eye. Symptoms may appear suddenly, and may include blurred vision, distortion of the size or shape of objects, floating black spots in the visual field, and/or impaired central vision. Diagnosis may be made by indirect evidence, which may include a lack of response to steroid therapy, positive test results for tuberculosis, and/or the ruling out of other causes for the uveitis. In some cases, tentative therapy for tuberculosis (i.e., the antimycobacterial drug isoniazid) may be administered to determine if the uveitis responds. If the treatment is effective Tuberculous Uveitis is the probable diagnosis.Macular Degeneration is the descriptive term for many forms of deterioration of the central area of vision (macula) from a previous state of normality. There are genetic, age-related, and environmental (including toxic) causes. Subtypes of the disorder include Stargardt's Disease and fundus flavimaculatus (occuring in children), and disciform macular degeneration (termed senile macular degeneration). Macular Degeneration caused by environmental elements may occur at any age. Major symptoms may include impaired or absent central vision with normal peripheral vision, a disturbance of vision in which shapes are distorted (metamorphopsia), and/or impaired central vision (central scotoma). (For more information on this disorder, choose “Macular Degeneration” as your search term in the Rare Disease Database.) | 236 | Choroiditis, Serpiginous |
nord_236_5 | Diagnosis of Choroiditis, Serpiginous | Diagnosis of Choroiditis, Serpiginous. | 236 | Choroiditis, Serpiginous |
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nord_236_6 | Therapies of Choroiditis, Serpiginous | Diagnosis of Serpiginous Choroiditis may be made by clinical evaluation and specialized ophthalmologic examinations such as electroretinography, electro-oculography, and/or fluorescein angiography. Widespread wasting (atrophy) of the choroid and retinal pigment epithelium membranes of the eye, pigment clumping, and/or deposits of fibrous tissue under the retina are characteristic findings.Periodic clinical examinations are recommended for people with Serpiginous Choroiditis to monitor the status of the disease and allow early detection of neovascular membrane development. Krypton or argon laser treatments may arrest the progress of neovascular membranes associated with Serpiginous Choroiditis.Treatment is not indicated unless the fovea of the retina is affected. When the fovea is involved, anti-inflammatory medication is recommended.Vision aids and/or specialized equipment (i.e., closed circuit television) may help to offset vision impairment associated with Serpiginous Choroiditis. Other treatment is symptomatic and supportive. | Therapies of Choroiditis, Serpiginous. Diagnosis of Serpiginous Choroiditis may be made by clinical evaluation and specialized ophthalmologic examinations such as electroretinography, electro-oculography, and/or fluorescein angiography. Widespread wasting (atrophy) of the choroid and retinal pigment epithelium membranes of the eye, pigment clumping, and/or deposits of fibrous tissue under the retina are characteristic findings.Periodic clinical examinations are recommended for people with Serpiginous Choroiditis to monitor the status of the disease and allow early detection of neovascular membrane development. Krypton or argon laser treatments may arrest the progress of neovascular membranes associated with Serpiginous Choroiditis.Treatment is not indicated unless the fovea of the retina is affected. When the fovea is involved, anti-inflammatory medication is recommended.Vision aids and/or specialized equipment (i.e., closed circuit television) may help to offset vision impairment associated with Serpiginous Choroiditis. Other treatment is symptomatic and supportive. | 236 | Choroiditis, Serpiginous |
nord_237_0 | Overview of Chromosome 10, Distal Trisomy 10q | Chromosome 10, distal trisomy 10q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of one chromosome 10 (10q) appears three times (trisomy) rather than twice in cells of the body. The disorder is characterized by unusually slow growth before and after birth); abnormally diminished muscle tone (hypotonia); mild to severe intellectual disability; and mild to severe delays in the acquisition of skills requiring coordination of mental and muscular activities. Affected infants and children may also have distinctive malformations of the head and facial (craniofacial) area; defects of the hands and/or feet; and/or skeletal, heart (cardiac), kidney (renal), and/or respiratory (pulmonary) abnormalities. The range and severity of symptoms and physical findings may vary from person to person, depending upon the exact length and location of the duplicated portion of chromosome 10q. In most cases, chromosome 10, distal trisomy 10q is due to a chromosomal balanced translocation in one of the parents. | Overview of Chromosome 10, Distal Trisomy 10q. Chromosome 10, distal trisomy 10q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of one chromosome 10 (10q) appears three times (trisomy) rather than twice in cells of the body. The disorder is characterized by unusually slow growth before and after birth); abnormally diminished muscle tone (hypotonia); mild to severe intellectual disability; and mild to severe delays in the acquisition of skills requiring coordination of mental and muscular activities. Affected infants and children may also have distinctive malformations of the head and facial (craniofacial) area; defects of the hands and/or feet; and/or skeletal, heart (cardiac), kidney (renal), and/or respiratory (pulmonary) abnormalities. The range and severity of symptoms and physical findings may vary from person to person, depending upon the exact length and location of the duplicated portion of chromosome 10q. In most cases, chromosome 10, distal trisomy 10q is due to a chromosomal balanced translocation in one of the parents. | 237 | Chromosome 10, Distal Trisomy 10q |
nord_237_1 | Symptoms of Chromosome 10, Distal Trisomy 10q | In individuals with chromosome 10, distal trisomy 10q, an extremely rare chromosomal disorder, the end (distal) portion of the long arm (q) of one chromosome 10 (10q) is duplicated (trisomic). Symptoms and physical characteristics associated with the disorder may vary greatly in range and severity, depending upon the exact size and location of the duplicated portion of chromosome 10q. However, in most patients, the disorder is characterized by mild to severe intellectual disability; distinctive malformations of the head and facial (craniofacial) area; also, there are sometimes defects of the hands and/or feet; and/or skeletal, heart (cardiac), kidney (renal), and/or respiratory (pulmonary) abnormalities. It is important to note that affected infants will not have all of the abnormalities listed below.In most cases, chromosome 10, distal trisomy 10q is characterized by abnormally slow growth before and after birth. In addition, most affected infants and children have mild to severely diminished muscle tone (hypotonia). Some may have abnormal looseness or laxity of the joints (generalized hyperlaxity). Infants and children with chromosome 10, distal trisomy 10q also have mild to severe intellectual disability and may experience profound delays in the acquisition of skills that require coordination of mental and muscular activities).In addition, infants and children with the disorder have characteristic malformations of the head and facial (craniofacial) area. Such abnormalities may include an abnormally small head (microcephaly) with a high, broad forehead; a round, slightly flattened face; prominent cheekbones; and/or low-set, misshapen ears that may appear rotated toward the back of the head (posteriorly rotated). Affected infants and children may also have a small nose with turned up nostrils (anteverted nares) and a broad, flat, and/or depressed nasal bridge; a small, bow-shaped mouth with a prominent upper lip; an unusually small lower jaw; and/or, in some patients, incomplete closure of the roof of the mouth (cleft palate). Additional features may include unusually fine, highly arched eyebrows; drooping of the upper eyelid(s) (ptosis); abnormal narrowing of the eyelid folds (palpebral fissures) between the upper and lower eyelids (blepharophimosis); and/or vertical skin folds that may cover the eyes’ inner corners (epicanthal folds). In some cases, according to the medical literature, the presence of epicanthal folds may cause the eyes to appear widely spaced (ocular hypertelorism). In addition, in some affected infants and children, the eyes may appear abnormally small (microphthalmia) due to reduced diameter of the cornea, the front, clear portion of the eye through which light passes.In some cases, infants and children with chromosome 10, distal trisomy 10q also have characteristic malformations of the hands and/or feet. Such abnormalities may include permanent flexion (camptodactyly) and/or overlapping of certain fingers; an unusually large distance between the great toes (hallux) and the second toes; webbing (syndactyly) between the second and third toes; and/or abnormal positioning of the feet (i.e., rocker-bottom feet). Affected infants and children may also have abnormal skin ridge patterns including underdeveloped (hypoplastic) ridge patterns on the hands and feet and/or abnormal deep grooves in the soles of the feet (plantar furrows).Many infants and children with the disorder may also have additional skeletal abnormalities. Affected individuals may have abnormally thin ribs, 11 rather than 12 rib pairs, an abnormally short neck, abnormal front-to-back and side-to side curvature of the spine (kyphoscoliosis), and/or abnormal depression of the sternum, the bone forming the center of the chest (“funnel chest” or pectus excavatum). Affected infants and children may also exhibit abnormally delayed, immature bone development (delayed bone age). In some cases, underdevelopment (hypoplasia) of the shin bone (tibia) and/or the thigh bone (femur).Approximately half of infants with chromosome 10, distal trisomy 10q may have defects of the heart that are present at birth (congenital heart defects), respiratory abnormalities, and/or malformations of the kidneys. Symptoms associated with congenital heart defects may vary greatly depending upon the exact nature, size, and location of the anatomical defect present. In some cases, associated symptoms and physical findings may include breathlessness due to the heart’s inability to pump blood effectively (heart failure); easy fatigability; bluish discoloration of the skin and mucous membranes (cyanosis) due to insufficient oxygen supply to these tissues; and/or increased susceptibility to repeated infections of the lungs (pneumonia). Renal malformations associated with chromosome 10, distal trisomy 10q may include underdevelopment of the kidneys (hypoplasia); development of cysts (cystic kidneys); and/or abnormal swelling (distention) of and accumulation of urine in the kidneys (hydronephrosis) and the tubes (ureters) that bring urine to the bladder (hydroureter). In severe cases, cardiac, respiratory, and/or renal abnormalities may result in life-threatening complications during the first years of life.In some cases, infants and children with chromosome 10, distal trisomy 10q may have additional abnormalities. In approximately half of affected males, one or both of the testes may fail to descend into the scrotum (cryptorchidism). | Symptoms of Chromosome 10, Distal Trisomy 10q. In individuals with chromosome 10, distal trisomy 10q, an extremely rare chromosomal disorder, the end (distal) portion of the long arm (q) of one chromosome 10 (10q) is duplicated (trisomic). Symptoms and physical characteristics associated with the disorder may vary greatly in range and severity, depending upon the exact size and location of the duplicated portion of chromosome 10q. However, in most patients, the disorder is characterized by mild to severe intellectual disability; distinctive malformations of the head and facial (craniofacial) area; also, there are sometimes defects of the hands and/or feet; and/or skeletal, heart (cardiac), kidney (renal), and/or respiratory (pulmonary) abnormalities. It is important to note that affected infants will not have all of the abnormalities listed below.In most cases, chromosome 10, distal trisomy 10q is characterized by abnormally slow growth before and after birth. In addition, most affected infants and children have mild to severely diminished muscle tone (hypotonia). Some may have abnormal looseness or laxity of the joints (generalized hyperlaxity). Infants and children with chromosome 10, distal trisomy 10q also have mild to severe intellectual disability and may experience profound delays in the acquisition of skills that require coordination of mental and muscular activities).In addition, infants and children with the disorder have characteristic malformations of the head and facial (craniofacial) area. Such abnormalities may include an abnormally small head (microcephaly) with a high, broad forehead; a round, slightly flattened face; prominent cheekbones; and/or low-set, misshapen ears that may appear rotated toward the back of the head (posteriorly rotated). Affected infants and children may also have a small nose with turned up nostrils (anteverted nares) and a broad, flat, and/or depressed nasal bridge; a small, bow-shaped mouth with a prominent upper lip; an unusually small lower jaw; and/or, in some patients, incomplete closure of the roof of the mouth (cleft palate). Additional features may include unusually fine, highly arched eyebrows; drooping of the upper eyelid(s) (ptosis); abnormal narrowing of the eyelid folds (palpebral fissures) between the upper and lower eyelids (blepharophimosis); and/or vertical skin folds that may cover the eyes’ inner corners (epicanthal folds). In some cases, according to the medical literature, the presence of epicanthal folds may cause the eyes to appear widely spaced (ocular hypertelorism). In addition, in some affected infants and children, the eyes may appear abnormally small (microphthalmia) due to reduced diameter of the cornea, the front, clear portion of the eye through which light passes.In some cases, infants and children with chromosome 10, distal trisomy 10q also have characteristic malformations of the hands and/or feet. Such abnormalities may include permanent flexion (camptodactyly) and/or overlapping of certain fingers; an unusually large distance between the great toes (hallux) and the second toes; webbing (syndactyly) between the second and third toes; and/or abnormal positioning of the feet (i.e., rocker-bottom feet). Affected infants and children may also have abnormal skin ridge patterns including underdeveloped (hypoplastic) ridge patterns on the hands and feet and/or abnormal deep grooves in the soles of the feet (plantar furrows).Many infants and children with the disorder may also have additional skeletal abnormalities. Affected individuals may have abnormally thin ribs, 11 rather than 12 rib pairs, an abnormally short neck, abnormal front-to-back and side-to side curvature of the spine (kyphoscoliosis), and/or abnormal depression of the sternum, the bone forming the center of the chest (“funnel chest” or pectus excavatum). Affected infants and children may also exhibit abnormally delayed, immature bone development (delayed bone age). In some cases, underdevelopment (hypoplasia) of the shin bone (tibia) and/or the thigh bone (femur).Approximately half of infants with chromosome 10, distal trisomy 10q may have defects of the heart that are present at birth (congenital heart defects), respiratory abnormalities, and/or malformations of the kidneys. Symptoms associated with congenital heart defects may vary greatly depending upon the exact nature, size, and location of the anatomical defect present. In some cases, associated symptoms and physical findings may include breathlessness due to the heart’s inability to pump blood effectively (heart failure); easy fatigability; bluish discoloration of the skin and mucous membranes (cyanosis) due to insufficient oxygen supply to these tissues; and/or increased susceptibility to repeated infections of the lungs (pneumonia). Renal malformations associated with chromosome 10, distal trisomy 10q may include underdevelopment of the kidneys (hypoplasia); development of cysts (cystic kidneys); and/or abnormal swelling (distention) of and accumulation of urine in the kidneys (hydronephrosis) and the tubes (ureters) that bring urine to the bladder (hydroureter). In severe cases, cardiac, respiratory, and/or renal abnormalities may result in life-threatening complications during the first years of life.In some cases, infants and children with chromosome 10, distal trisomy 10q may have additional abnormalities. In approximately half of affected males, one or both of the testes may fail to descend into the scrotum (cryptorchidism). | 237 | Chromosome 10, Distal Trisomy 10q |
nord_237_2 | Causes of Chromosome 10, Distal Trisomy 10q | Chromosome 10, distal trisomy 10q is an extremely rare chromosomal disorder in which part of the end (distal) portion of the long arm (q) of one chromosome 10 is duplicated. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The duplication of the distal portion of chromosome 10q is responsible for the symptoms and physical features that characterize this disorder. The range and severity of symptoms depend upon the exact length and location of the duplicated portion of chromosome 10q. In individuals with the disorder, the duplicated portion of 10q may begin as high on the chromosome as in band 10q22, or as far down as in band 10q25 and usually extends toward the end or “terminal” portion of chromosome 10q (qter); According to the medical literature, researchers suspect that duplication of bands 10q25 and 10q26 is critical for the expression of the characteristic features associated with the disorder. Often heart and kidney defects are related to the duplication of band 10q24.In over 90 percent of reported cases, chromosome 10, distal trisomy 10q is due to a chromosomal balanced translocation in one of the parents. A translocation is said to be “balanced” if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes. Balanced translocations are usually harmless to the carrier. However, in some cases, carriers may have reproductive cells (i.e., eggs in females, sperm cells in males) with an “unbalanced” set of chromosomes. Therefore, carriers of a balanced translocation may have an increased risk of having offspring with an unbalanced translocation (i.e., an altered set of chromosomes resulting in extra and/or missing chromosomal material in certain chromosomal locations). Chromosomal testing may determine whether a parent has a balanced translocation. If a child has partial trisomy 10q due to a parental translocation, they may also have a partial monosomy of another chromosome.In some cases, chromosome 10, distal trisomy 10q may be due to a spontaneous (de novo) genetic change (mutation) that occurs for unknown reasons (sporadic). In such cases, because the mutation is not related to parental chromosomal makeup, the chromosomal abnormality is not inherited from the parents. | Causes of Chromosome 10, Distal Trisomy 10q. Chromosome 10, distal trisomy 10q is an extremely rare chromosomal disorder in which part of the end (distal) portion of the long arm (q) of one chromosome 10 is duplicated. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The duplication of the distal portion of chromosome 10q is responsible for the symptoms and physical features that characterize this disorder. The range and severity of symptoms depend upon the exact length and location of the duplicated portion of chromosome 10q. In individuals with the disorder, the duplicated portion of 10q may begin as high on the chromosome as in band 10q22, or as far down as in band 10q25 and usually extends toward the end or “terminal” portion of chromosome 10q (qter); According to the medical literature, researchers suspect that duplication of bands 10q25 and 10q26 is critical for the expression of the characteristic features associated with the disorder. Often heart and kidney defects are related to the duplication of band 10q24.In over 90 percent of reported cases, chromosome 10, distal trisomy 10q is due to a chromosomal balanced translocation in one of the parents. A translocation is said to be “balanced” if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes. Balanced translocations are usually harmless to the carrier. However, in some cases, carriers may have reproductive cells (i.e., eggs in females, sperm cells in males) with an “unbalanced” set of chromosomes. Therefore, carriers of a balanced translocation may have an increased risk of having offspring with an unbalanced translocation (i.e., an altered set of chromosomes resulting in extra and/or missing chromosomal material in certain chromosomal locations). Chromosomal testing may determine whether a parent has a balanced translocation. If a child has partial trisomy 10q due to a parental translocation, they may also have a partial monosomy of another chromosome.In some cases, chromosome 10, distal trisomy 10q may be due to a spontaneous (de novo) genetic change (mutation) that occurs for unknown reasons (sporadic). In such cases, because the mutation is not related to parental chromosomal makeup, the chromosomal abnormality is not inherited from the parents. | 237 | Chromosome 10, Distal Trisomy 10q |
nord_237_3 | Affects of Chromosome 10, Distal Trisomy 10q | Chromosome 10, distal trisomy 10q is an extremely rare but well-defined chromosomal disorder that appears to affect males and females at about the same rate. More than 35 cases have been reported in the medical literature since the disorder was originally described in 1974 (J.J. Yunis). Many of the symptoms and physical features associated with the disorder are apparent at birth (congenital). | Affects of Chromosome 10, Distal Trisomy 10q. Chromosome 10, distal trisomy 10q is an extremely rare but well-defined chromosomal disorder that appears to affect males and females at about the same rate. More than 35 cases have been reported in the medical literature since the disorder was originally described in 1974 (J.J. Yunis). Many of the symptoms and physical features associated with the disorder are apparent at birth (congenital). | 237 | Chromosome 10, Distal Trisomy 10q |
nord_237_4 | Related disorders of Chromosome 10, Distal Trisomy 10q | Symptoms of the following disorders may be similar to those of Chromosome 10, Distal Trisomy 10q. Comparisons may be useful for a differential diagnosis:Chromosome 10, Monosomy 10p is a very rare chromosomal disorder in which the end (distal) portion of the short arm (p) of one chromosome 10 is missing (deleted or monosomic). The disorder is characterized by growth delays and short stature, developmental delays, characteristic abnormalities of the head and facial (craniofacial) area, congenital heart defects, urinary tract malformations, and/or failure of one or both of the testes to descend into the scrotum (cryptorchidism) in affected males. Characteristic craniofacial malformations may include an abnormally small head (microcephaly) with an unusually prominent forehead (frontal bossing); a small, underdeveloped jaw (micrognathia); drooping of the upper eyelid(s) (ptosis); downslanting eyelid folds (palpebral fissures); small, misshapen ears; and/or other abnormalities. In most cases, the disorder is due to a spontaneous (de novo) genetic change (mutation) that occurs for unknown reasons (sporadic). (For more information on this disorder, choose “Monosomy 10p” as your search term in the Rare Disease Database.)There are additional chromosomal disorders that may be characterized by slow growth before and after birth, intellectual and psychomotor disability, craniofacial abnormalities, malformations of the hands and feet, and/or cardiac, respiratory, and/or renal abnormalities similar to those occurring in association with Chromosome 10, Distal Trisomy 10q. The only way to determine which chromosomal disorder an individual has is through chromosomal testing. (For more information on these disorders, choose the exact disease name in question or “Chromosome” as your search term in the Rare Disease Database.) | Related disorders of Chromosome 10, Distal Trisomy 10q. Symptoms of the following disorders may be similar to those of Chromosome 10, Distal Trisomy 10q. Comparisons may be useful for a differential diagnosis:Chromosome 10, Monosomy 10p is a very rare chromosomal disorder in which the end (distal) portion of the short arm (p) of one chromosome 10 is missing (deleted or monosomic). The disorder is characterized by growth delays and short stature, developmental delays, characteristic abnormalities of the head and facial (craniofacial) area, congenital heart defects, urinary tract malformations, and/or failure of one or both of the testes to descend into the scrotum (cryptorchidism) in affected males. Characteristic craniofacial malformations may include an abnormally small head (microcephaly) with an unusually prominent forehead (frontal bossing); a small, underdeveloped jaw (micrognathia); drooping of the upper eyelid(s) (ptosis); downslanting eyelid folds (palpebral fissures); small, misshapen ears; and/or other abnormalities. In most cases, the disorder is due to a spontaneous (de novo) genetic change (mutation) that occurs for unknown reasons (sporadic). (For more information on this disorder, choose “Monosomy 10p” as your search term in the Rare Disease Database.)There are additional chromosomal disorders that may be characterized by slow growth before and after birth, intellectual and psychomotor disability, craniofacial abnormalities, malformations of the hands and feet, and/or cardiac, respiratory, and/or renal abnormalities similar to those occurring in association with Chromosome 10, Distal Trisomy 10q. The only way to determine which chromosomal disorder an individual has is through chromosomal testing. (For more information on these disorders, choose the exact disease name in question or “Chromosome” as your search term in the Rare Disease Database.) | 237 | Chromosome 10, Distal Trisomy 10q |
nord_237_5 | Diagnosis of Chromosome 10, Distal Trisomy 10q | In some cases, the diagnosis of Chromosome 10, Distal Trisomy 10q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Laboratory studies performed on this fluid or tissue sample may reveal the presence of Distal Trisomy 10q.Chromosome 10, Distal Trisomy 10q may also be diagnosed and/or confirmed after birth (postnatally) based upon a thorough clinical evaluation, identification of characteristic physical findings, and chromosomal studies. Small trisomies may not be detected on standard chromosomal studies and may require chromosomal microarray analysis.Certain specific abnormalities that may occur in association with Distal Trisomy 10q may be detected and/or confirmed by specialized imaging studies and/or additional tests. For example, specialized x-ray studies and/or other imaging techniques may be used to confirm and/or characterize certain skeletal abnormalities and/or renal malformations potentially associated with the disorder. Congenital heart defects potentially associated with Chromosome 10, Distal Trisomy 10q may be detected, confirmed, and/or characterized by a thorough clinical evaluation and specialized tests that allow physicians to evaluate the structure and function of the heart (e.g., x-ray studies, electrocardiogram [EKG] echocardiogram, cardiac catherization). | Diagnosis of Chromosome 10, Distal Trisomy 10q. In some cases, the diagnosis of Chromosome 10, Distal Trisomy 10q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Laboratory studies performed on this fluid or tissue sample may reveal the presence of Distal Trisomy 10q.Chromosome 10, Distal Trisomy 10q may also be diagnosed and/or confirmed after birth (postnatally) based upon a thorough clinical evaluation, identification of characteristic physical findings, and chromosomal studies. Small trisomies may not be detected on standard chromosomal studies and may require chromosomal microarray analysis.Certain specific abnormalities that may occur in association with Distal Trisomy 10q may be detected and/or confirmed by specialized imaging studies and/or additional tests. For example, specialized x-ray studies and/or other imaging techniques may be used to confirm and/or characterize certain skeletal abnormalities and/or renal malformations potentially associated with the disorder. Congenital heart defects potentially associated with Chromosome 10, Distal Trisomy 10q may be detected, confirmed, and/or characterized by a thorough clinical evaluation and specialized tests that allow physicians to evaluate the structure and function of the heart (e.g., x-ray studies, electrocardiogram [EKG] echocardiogram, cardiac catherization). | 237 | Chromosome 10, Distal Trisomy 10q |
nord_237_6 | Therapies of Chromosome 10, Distal Trisomy 10q | TreatmentThe treatment of Chromosome 10, Distal Trisomy 10q is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians; surgeons; physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), disorders or malformations of the heart (cardiologists), or kidney abnormalities (nephrologists); physical therapists; and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.The treatment of Chromosome 10, Distal Trisomy 10q is symptomatic and supportive. In some cases, surgery may be performed to correct certain craniofacial, skeletal, cardiac, renal, and/or other malformations that may be associated with the disorder. In such cases, the surgical procedures performed will depend upon the location and severity of the anatomical abnormalities and their associated symptoms.Physicians may recommend preventive measures for affected infants and children who may be prone to repeated respiratory infections. Physicians may also regularly monitor affected individuals for such infections to ensure early detection and appropriate, prompt treatment.A team approach for infants and children with this disorder may be of benefit and may include special medical, educational, and social support services. Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive. | Therapies of Chromosome 10, Distal Trisomy 10q. TreatmentThe treatment of Chromosome 10, Distal Trisomy 10q is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians; surgeons; physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), disorders or malformations of the heart (cardiologists), or kidney abnormalities (nephrologists); physical therapists; and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.The treatment of Chromosome 10, Distal Trisomy 10q is symptomatic and supportive. In some cases, surgery may be performed to correct certain craniofacial, skeletal, cardiac, renal, and/or other malformations that may be associated with the disorder. In such cases, the surgical procedures performed will depend upon the location and severity of the anatomical abnormalities and their associated symptoms.Physicians may recommend preventive measures for affected infants and children who may be prone to repeated respiratory infections. Physicians may also regularly monitor affected individuals for such infections to ensure early detection and appropriate, prompt treatment.A team approach for infants and children with this disorder may be of benefit and may include special medical, educational, and social support services. Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive. | 237 | Chromosome 10, Distal Trisomy 10q |
nord_238_0 | Overview of Chromosome 10, Monosomy 10p | Chromosome 10, monosomy 10p is a rare chromosomal disorder in which the end (distal) portion of the short arm (p) of chromosome 10 is missing (deleted or monosomic). The range and severity of symptoms and findings may be variable, depending upon the exact size or location of the deletion on chromosome 10p. However, associated features often include severe intellectual disability; growth delays after birth (postnatal growth retardation); distinctive malformations of the skull and facial (craniofacial) region; a short neck; and/or structural defects of the heart that are present at birth (congenital heart defects). Several cases have also been reported in which affected individuals have some features of DiGeorge syndrome (DGS). DGS is a congenital disorder characterized by underdevelopment or absence of the thymus and parathyroid glands, potentially causing abnormalities of the immune system, deficient production of parathyroid hormone (hypoparathyroidism), a heart defect, and associated findings. In many cases, chromosome 10, monosomy 10p appears to occur spontaneously (de novo) for unknown reasons. | Overview of Chromosome 10, Monosomy 10p. Chromosome 10, monosomy 10p is a rare chromosomal disorder in which the end (distal) portion of the short arm (p) of chromosome 10 is missing (deleted or monosomic). The range and severity of symptoms and findings may be variable, depending upon the exact size or location of the deletion on chromosome 10p. However, associated features often include severe intellectual disability; growth delays after birth (postnatal growth retardation); distinctive malformations of the skull and facial (craniofacial) region; a short neck; and/or structural defects of the heart that are present at birth (congenital heart defects). Several cases have also been reported in which affected individuals have some features of DiGeorge syndrome (DGS). DGS is a congenital disorder characterized by underdevelopment or absence of the thymus and parathyroid glands, potentially causing abnormalities of the immune system, deficient production of parathyroid hormone (hypoparathyroidism), a heart defect, and associated findings. In many cases, chromosome 10, monosomy 10p appears to occur spontaneously (de novo) for unknown reasons. | 238 | Chromosome 10, Monosomy 10p |
nord_238_1 | Symptoms of Chromosome 10, Monosomy 10p | The symptoms and physical findings associated with chromosome 10, monosomy 10p may vary in range and severity from case to case. However, according to reports in the medical literature, most individuals with the disorder are affected by severe intellectual disability and delays in the acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation). Monosomy 10p is also frequently associated with growth delays after birth, resulting in short stature.Affected infants and children also typically have certain distinctive abnormalities of the skull and facial (craniofacial) region. Such malformations may include an abnormally small head (microcephaly) with a protruding forehead (frontal bossing); a small jaw (micrognathia); a low nasal bridge and upturned (anteverted) nostrils; malformed, low set ears; and a short neck. Additional craniofacial defects may also be present, such as widely spaced eyes (ocular hypertelorism); short, downwardly slanting eyelid folds (palpebral fissures); vertical skin folds covering the eyes' inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); and abnormal deviation of one eye in relation to the other (strabismus). Less commonly, the disorder may be associated with incomplete closure of the roof of the mouth (cleft palate) and an abnormal groove in the upper lip (cleft lip).Individuals with monosomy 10p may also have widely spaced nipples; foot malformations; and/or structural defects of the heart (congenital heart defects). In addition, the disorder may be associated with abnormalities of the urinary tract and the genitals, such as undescended testes (cryptorchidism) and an underdeveloped (hypoplastic) scrotum in affected males. Some individuals may also have dysfunction of the lowest region of the brain known as the brainstem, which helps to convey messages traveling between other brain regions and the spinal cord and has sensory, motor, and reflex functions. In individuals with monosomy 10p, brainstem dysfunction may be associated with severe hearing loss due to impaired conversion of sound vibrations and failed transmission of nerve impulses from the inner ear via the auditory nerve to the brain (i.e., sensorineural hearing loss).As mentioned previously, monosomy 10p may often be associated with features of DiGeorge syndrome (DGS). DGS is a congenital disorder resulting from improper development of embryonic structures that form the thymus and parathyroid glands. Other embryonic structures that develop at about the same time may also sometimes be affected, potentially leading to certain defects of the heart and its major blood vessels (cardiovascular defects) and/or craniofacial malformations. The thymus is thought to play a crucial role in the body's immune system beginning during fetal development until about puberty. It serves to promote the maturation of certain precursor* cells into T lymphocytes, which are specialized white blood cells that assist in the recognition or destruction of foreign proteins (antigens), such as certain invading microorganisms. (*A precursor is a biological forerunner or a substance that precedes and is the source of another, typically more mature or active substance.) The parathyroid glands are two pairs of relatively small glands that produce parathyroid hormone, which helps to regulate blood calcium levels.Individuals with monosomy 10p who have features of DGS typically have variable degrees of hypoplasia or underdevelopment of the thymus and parathyroid glands. This is sometimes referred to as “partial DiGeorge syndrome.” Hypoplasia of the thymus may lead to deficient activity of the immune system and impaired resistance to certain viral, bacterial, or fungal infections. In other cases, however, some individuals with partial DiGeorge syndrome may not appear to have an increased susceptibility to recurrent infections.In those with hypoplasia of the parathyroid glands, deficient secretion of parathyroid hormone (hypoparathyroidism) may lead to low calcium blood levels (hypocalcemia) and associated findings during the first days of life (neonatal tetany). Such features may include muscle cramping and spasms, convulsions, tremors, spasmodic closure of the larynx (laryngospasm), and/or other findings. Cardiovascular abnormalities that have been reported in association with DGS include defects of the aorta or the major artery that supplies oxygenated blood to most of the body; an abnormal opening in the fibrous partition (septum) that separates the lower or upper chambers of the heart (ventricular or atrial septal defects); and/or other congenital defects.Experts suggest that certain abnormalities frequently seen in individuals with monosomy 10p may be absent in those with classic DiGeorge syndrome (i.e., DGS that results from minute deletions of material from the long arm of chromosome 22). For example, severe intellectual disability and growth delays are seen in most individuals with monosomy 10p yet may not be apparent in those with classic DGS. Sensorineural deafness, a finding reported in a number of individuals with monosomy 10p, has not been associated with classic DGS. In addition, abnormalities of the heart and its major blood vessels are more frequent in classic DGS than monosomy 10p. (For further information, please see the “Causes” section of this report below.) | Symptoms of Chromosome 10, Monosomy 10p. The symptoms and physical findings associated with chromosome 10, monosomy 10p may vary in range and severity from case to case. However, according to reports in the medical literature, most individuals with the disorder are affected by severe intellectual disability and delays in the acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation). Monosomy 10p is also frequently associated with growth delays after birth, resulting in short stature.Affected infants and children also typically have certain distinctive abnormalities of the skull and facial (craniofacial) region. Such malformations may include an abnormally small head (microcephaly) with a protruding forehead (frontal bossing); a small jaw (micrognathia); a low nasal bridge and upturned (anteverted) nostrils; malformed, low set ears; and a short neck. Additional craniofacial defects may also be present, such as widely spaced eyes (ocular hypertelorism); short, downwardly slanting eyelid folds (palpebral fissures); vertical skin folds covering the eyes' inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); and abnormal deviation of one eye in relation to the other (strabismus). Less commonly, the disorder may be associated with incomplete closure of the roof of the mouth (cleft palate) and an abnormal groove in the upper lip (cleft lip).Individuals with monosomy 10p may also have widely spaced nipples; foot malformations; and/or structural defects of the heart (congenital heart defects). In addition, the disorder may be associated with abnormalities of the urinary tract and the genitals, such as undescended testes (cryptorchidism) and an underdeveloped (hypoplastic) scrotum in affected males. Some individuals may also have dysfunction of the lowest region of the brain known as the brainstem, which helps to convey messages traveling between other brain regions and the spinal cord and has sensory, motor, and reflex functions. In individuals with monosomy 10p, brainstem dysfunction may be associated with severe hearing loss due to impaired conversion of sound vibrations and failed transmission of nerve impulses from the inner ear via the auditory nerve to the brain (i.e., sensorineural hearing loss).As mentioned previously, monosomy 10p may often be associated with features of DiGeorge syndrome (DGS). DGS is a congenital disorder resulting from improper development of embryonic structures that form the thymus and parathyroid glands. Other embryonic structures that develop at about the same time may also sometimes be affected, potentially leading to certain defects of the heart and its major blood vessels (cardiovascular defects) and/or craniofacial malformations. The thymus is thought to play a crucial role in the body's immune system beginning during fetal development until about puberty. It serves to promote the maturation of certain precursor* cells into T lymphocytes, which are specialized white blood cells that assist in the recognition or destruction of foreign proteins (antigens), such as certain invading microorganisms. (*A precursor is a biological forerunner or a substance that precedes and is the source of another, typically more mature or active substance.) The parathyroid glands are two pairs of relatively small glands that produce parathyroid hormone, which helps to regulate blood calcium levels.Individuals with monosomy 10p who have features of DGS typically have variable degrees of hypoplasia or underdevelopment of the thymus and parathyroid glands. This is sometimes referred to as “partial DiGeorge syndrome.” Hypoplasia of the thymus may lead to deficient activity of the immune system and impaired resistance to certain viral, bacterial, or fungal infections. In other cases, however, some individuals with partial DiGeorge syndrome may not appear to have an increased susceptibility to recurrent infections.In those with hypoplasia of the parathyroid glands, deficient secretion of parathyroid hormone (hypoparathyroidism) may lead to low calcium blood levels (hypocalcemia) and associated findings during the first days of life (neonatal tetany). Such features may include muscle cramping and spasms, convulsions, tremors, spasmodic closure of the larynx (laryngospasm), and/or other findings. Cardiovascular abnormalities that have been reported in association with DGS include defects of the aorta or the major artery that supplies oxygenated blood to most of the body; an abnormal opening in the fibrous partition (septum) that separates the lower or upper chambers of the heart (ventricular or atrial septal defects); and/or other congenital defects.Experts suggest that certain abnormalities frequently seen in individuals with monosomy 10p may be absent in those with classic DiGeorge syndrome (i.e., DGS that results from minute deletions of material from the long arm of chromosome 22). For example, severe intellectual disability and growth delays are seen in most individuals with monosomy 10p yet may not be apparent in those with classic DGS. Sensorineural deafness, a finding reported in a number of individuals with monosomy 10p, has not been associated with classic DGS. In addition, abnormalities of the heart and its major blood vessels are more frequent in classic DGS than monosomy 10p. (For further information, please see the “Causes” section of this report below.) | 238 | Chromosome 10, Monosomy 10p |
nord_238_2 | Causes of Chromosome 10, Monosomy 10p | Chromosome 10, monosomy 10p is a rare chromosomal abnormality in which there is deletion (monosomy) of the end (distal) portion of the short arm (p) of chromosome 10. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered.In individuals with monosomy 10p, the range and severity of associated symptoms and findings may vary, depending upon the exact length or location of the deleted portion of chromosome 10p. Deletions occurring closer to the centromere result in in a phenotype with similar features to DiGeorge syndrome, as discussed. More distal deletions are associated with mutations in a specific gene, GATA3, resulting in hypoparathyroidism (see “symptoms” section), deafness, and renal (kidney) abnormalities, and refered to as HDR syndrome. The GATA3 gene encodes a protein involved in the embryonic development of these three tissues, i.e. parathyroid glands, auditory system, and kidneys. A recent study carried out molecular and clinical characterization of patients with overlapping 10p deletions. These studies showed that individuals with partial deletions 10p14-p15 may exhibit severe intellectual disability, language impairments and autistic behaviors. In some cases, monosomy 10p appears to occur spontaneously (de novo) for unknown reasons very early in embryonic development. The parents of a child with a “de novo” deletion usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. In other cases, monosomy 10p may result from a translocation involving chromosome 10p and another chromosome or chromosomes. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. Such translocations may occur spontaneously for unknown reasons (de novo) or be transmitted by a parent who is a carrier of a “balanced” translocation. (If a chromosomal rearrangement is balanced–i.e., consists of an altered but balanced set of chromosomes–it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier's offspring. Chromosomal analysis may determine whether a parent has a balanced translocation.)As mentioned above, monosomy 10p may often be associated with features of DiGeorge syndrome (DGS), a condition caused by abnormal development of embryonic structures that form the thymus and parathyroid glands and, in some instances, other embryonic structures. DGS most commonly results from spontaneous (sporadic), minute deletions (microdeletions) of material from the long arm (q) of chromosome 22 (22q11.2 [known as the “DiGeorge syndrome chromosomal region” or “DGCR”). Such cases are sometimes referred to as “classical DiGeorge syndrome.” However, phenotypes similar to those observed in DiGeorge syndrome can also have other underlying causes, such as various chromosomal abnormalities, including monosomy 10p and fetal exposure to alcohol or certain vitamin A-like compounds (retinoids) during pregnancy. (For further information on classic DiGeorge syndrome, please use “DiGeorge” as your search term in the Rare Disease Database. For more on chromosome 22, deletion 22q11.2, please see the “Related Disorders” section below.) | Causes of Chromosome 10, Monosomy 10p. Chromosome 10, monosomy 10p is a rare chromosomal abnormality in which there is deletion (monosomy) of the end (distal) portion of the short arm (p) of chromosome 10. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered.In individuals with monosomy 10p, the range and severity of associated symptoms and findings may vary, depending upon the exact length or location of the deleted portion of chromosome 10p. Deletions occurring closer to the centromere result in in a phenotype with similar features to DiGeorge syndrome, as discussed. More distal deletions are associated with mutations in a specific gene, GATA3, resulting in hypoparathyroidism (see “symptoms” section), deafness, and renal (kidney) abnormalities, and refered to as HDR syndrome. The GATA3 gene encodes a protein involved in the embryonic development of these three tissues, i.e. parathyroid glands, auditory system, and kidneys. A recent study carried out molecular and clinical characterization of patients with overlapping 10p deletions. These studies showed that individuals with partial deletions 10p14-p15 may exhibit severe intellectual disability, language impairments and autistic behaviors. In some cases, monosomy 10p appears to occur spontaneously (de novo) for unknown reasons very early in embryonic development. The parents of a child with a “de novo” deletion usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. In other cases, monosomy 10p may result from a translocation involving chromosome 10p and another chromosome or chromosomes. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. Such translocations may occur spontaneously for unknown reasons (de novo) or be transmitted by a parent who is a carrier of a “balanced” translocation. (If a chromosomal rearrangement is balanced–i.e., consists of an altered but balanced set of chromosomes–it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier's offspring. Chromosomal analysis may determine whether a parent has a balanced translocation.)As mentioned above, monosomy 10p may often be associated with features of DiGeorge syndrome (DGS), a condition caused by abnormal development of embryonic structures that form the thymus and parathyroid glands and, in some instances, other embryonic structures. DGS most commonly results from spontaneous (sporadic), minute deletions (microdeletions) of material from the long arm (q) of chromosome 22 (22q11.2 [known as the “DiGeorge syndrome chromosomal region” or “DGCR”). Such cases are sometimes referred to as “classical DiGeorge syndrome.” However, phenotypes similar to those observed in DiGeorge syndrome can also have other underlying causes, such as various chromosomal abnormalities, including monosomy 10p and fetal exposure to alcohol or certain vitamin A-like compounds (retinoids) during pregnancy. (For further information on classic DiGeorge syndrome, please use “DiGeorge” as your search term in the Rare Disease Database. For more on chromosome 22, deletion 22q11.2, please see the “Related Disorders” section below.) | 238 | Chromosome 10, Monosomy 10p |
nord_238_3 | Affects of Chromosome 10, Monosomy 10p | Chromosome 10, monosomy 10p is typically evident at birth (congenital). Since the disorder was originally reported in the medical literature in 1970, over 46 cases have been recorded. In such observed cases, males appear to be more frequently affected than females. | Affects of Chromosome 10, Monosomy 10p. Chromosome 10, monosomy 10p is typically evident at birth (congenital). Since the disorder was originally reported in the medical literature in 1970, over 46 cases have been recorded. In such observed cases, males appear to be more frequently affected than females. | 238 | Chromosome 10, Monosomy 10p |
nord_238_4 | Related disorders of Chromosome 10, Monosomy 10p | Symptoms of the following disorders may also be similar to those of chromosome 10, monosomy 10p. Comparisons may be useful for a differential diagnosis:Chromosome 22, deletion 22q11.2 is a rare chromosomal disorder in which there is deletion of the long arm of chromosome 22. Individuals with deletions involving band q11.2 (i.e., DGCR) are affected by DiGeorge syndrome, including underdevelopment or absence of the thymus and potentially increased susceptibility to certain infections; hypoparathyroidism; and, in some cases, cardiovascular defects. Deletions that involve the end (distal) portion of chromosome 22q may also be associated with severe mental and psychomotor retardation; poor muscle tone (hypotonia); characteristic craniofacial features; and skeletal defects. Craniofacial abnormalities may include an abnormally small head (microcephaly); deeply set eyes; vertical skin folds that cover the eyes' inner corners (epicanthal folds); low, full eyebrows and long eyelashes; a broad, bulbous nose; and an abnormally long vertical groove in the center of the upper lip (philtrum). Affected individuals may also have abnormal front-to-back curvature of the spine (kyphosis), unusually short fingers, and/or other abnormalities. This syndrome may appear to occur spontaneously (de novo) for unknown reasons or result from a parental balanced translocation involving chromosome 22q and another chromosome.Additional chromosomal disorders may have features similar to those associated with chromosome 10, monosomy 10p. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database.) | Related disorders of Chromosome 10, Monosomy 10p. Symptoms of the following disorders may also be similar to those of chromosome 10, monosomy 10p. Comparisons may be useful for a differential diagnosis:Chromosome 22, deletion 22q11.2 is a rare chromosomal disorder in which there is deletion of the long arm of chromosome 22. Individuals with deletions involving band q11.2 (i.e., DGCR) are affected by DiGeorge syndrome, including underdevelopment or absence of the thymus and potentially increased susceptibility to certain infections; hypoparathyroidism; and, in some cases, cardiovascular defects. Deletions that involve the end (distal) portion of chromosome 22q may also be associated with severe mental and psychomotor retardation; poor muscle tone (hypotonia); characteristic craniofacial features; and skeletal defects. Craniofacial abnormalities may include an abnormally small head (microcephaly); deeply set eyes; vertical skin folds that cover the eyes' inner corners (epicanthal folds); low, full eyebrows and long eyelashes; a broad, bulbous nose; and an abnormally long vertical groove in the center of the upper lip (philtrum). Affected individuals may also have abnormal front-to-back curvature of the spine (kyphosis), unusually short fingers, and/or other abnormalities. This syndrome may appear to occur spontaneously (de novo) for unknown reasons or result from a parental balanced translocation involving chromosome 22q and another chromosome.Additional chromosomal disorders may have features similar to those associated with chromosome 10, monosomy 10p. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database.) | 238 | Chromosome 10, Monosomy 10p |
nord_238_5 | Diagnosis of Chromosome 10, Monosomy 10p | In some cases, a diagnosis of chromosome 10, monosomy 10p may be suggested before birth (prenatally) by tests such as amniocentesis or chorionic villus sampling (CVS). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed. CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on the fluid or tissue samples may reveal the presence of monosomy 10p.Chromosome 10, monosomy 10p may also be diagnosed or confirmed after birth based upon a thorough clinical evaluation, detection of characteristic physical findings, andcytogeneticanalysis, either by G-banded karyotype analysis or chromosomal microarray analysis. Specialized tests may also be conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder. These may include tests to assess blood calcium levels; immunologic studies; advanced imaging techniques to confirm or characterize abnormalities of the thymus, parathyroid glands, and brain (e.g., ultrasonography, computed tomography [CT] scanning, magnetic resonance imaging [MRI]); and studies to evaluate the structure and function of the heart (e.g., x-ray imaging, electrocardiogram [EKG], echocardiogram, cardiac catheterization). Testing known as brainstem auditory evoked response (BAER) may also be conducted to screen affected infants for hearing impairment. During BAER, clicking sounds are used and responses are recorded to evaluate hearing (auditory) pathways of the brainstem. In some cases, additional diagnostic studies may also be recommended. | Diagnosis of Chromosome 10, Monosomy 10p. In some cases, a diagnosis of chromosome 10, monosomy 10p may be suggested before birth (prenatally) by tests such as amniocentesis or chorionic villus sampling (CVS). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed. CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on the fluid or tissue samples may reveal the presence of monosomy 10p.Chromosome 10, monosomy 10p may also be diagnosed or confirmed after birth based upon a thorough clinical evaluation, detection of characteristic physical findings, andcytogeneticanalysis, either by G-banded karyotype analysis or chromosomal microarray analysis. Specialized tests may also be conducted to help detect and/or characterize certain abnormalities that may be associated with the disorder. These may include tests to assess blood calcium levels; immunologic studies; advanced imaging techniques to confirm or characterize abnormalities of the thymus, parathyroid glands, and brain (e.g., ultrasonography, computed tomography [CT] scanning, magnetic resonance imaging [MRI]); and studies to evaluate the structure and function of the heart (e.g., x-ray imaging, electrocardiogram [EKG], echocardiogram, cardiac catheterization). Testing known as brainstem auditory evoked response (BAER) may also be conducted to screen affected infants for hearing impairment. During BAER, clicking sounds are used and responses are recorded to evaluate hearing (auditory) pathways of the brainstem. In some cases, additional diagnostic studies may also be recommended. | 238 | Chromosome 10, Monosomy 10p |
nord_238_6 | Therapies of Chromosome 10, Monosomy 10p | TreatmentThe treatment of Chromosome 10, monosomy 10p is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; specialists in the functioning of the immune system (immunologists); endocrine disorder specialists (endocrinologists); physicians who diagnose and treat heart abnormalities (cardiologists); hearing specialists; and/or other health care professionals.The treatment of affected individuals is symptomatic and supportive. For those with hypoparathyroidism, treatment may include administration of calcium and vitamin D, which aids in calcium absorption. For individuals with an increased susceptibility to recurrent infections, the use of particular antibiotic, antiviral, and antifungal medications and other agents may be required to help prevent and aggressively treat certain infections. (For further information on disease management for features of DiGeorge syndrome, please choose "DiGeorge" as your search term in the Rare Disease Database.)Physicians may also recommend corrective surgery for certain craniofacial and/or other malformations potentially associated with monosomy 10p. In addition, for those with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be necessary. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for families of affected children. Other treatment for this disorder is symptomatic and supportive. | Therapies of Chromosome 10, Monosomy 10p. TreatmentThe treatment of Chromosome 10, monosomy 10p is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; specialists in the functioning of the immune system (immunologists); endocrine disorder specialists (endocrinologists); physicians who diagnose and treat heart abnormalities (cardiologists); hearing specialists; and/or other health care professionals.The treatment of affected individuals is symptomatic and supportive. For those with hypoparathyroidism, treatment may include administration of calcium and vitamin D, which aids in calcium absorption. For individuals with an increased susceptibility to recurrent infections, the use of particular antibiotic, antiviral, and antifungal medications and other agents may be required to help prevent and aggressively treat certain infections. (For further information on disease management for features of DiGeorge syndrome, please choose "DiGeorge" as your search term in the Rare Disease Database.)Physicians may also recommend corrective surgery for certain craniofacial and/or other malformations potentially associated with monosomy 10p. In addition, for those with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be necessary. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for families of affected children. Other treatment for this disorder is symptomatic and supportive. | 238 | Chromosome 10, Monosomy 10p |
nord_239_0 | Overview of Chromosome 11, Partial Monosomy 11q | Partial monosomy 11q syndrome is a rare chromosomal disorder in which a portion of the long arm of chromosome 11 is deleted (missing). Jacobsen syndrome is observed in SOME patients with 11q partial deletion. The region consistently missing in individuals with this disorder (JS) is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (this chromosome region is called the Jacobsen syndrome critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests (with or without the FISH staining technique), and CGH array.An 11q deletion involving regions ouside the JS crititcal region causes a different genetic condition.The range and severity of symptoms varies, greatly depending on the exact location and size of the missing genetic material. Symptoms commonly associated with partial monosomy 11q include abnormally slow growth before and after birth (prenatal and postnatal growth delay), moderate to severe delay in skills requiring coordination of mental and muscular activity and intellectual disability Most affected persons have mild to severe intellectual disability but rarely, individuals may have normal-borderline intelligence. Characteristic physical abnormalities may include short stature, unusual shape of the head and face (craniofacial dysmorphism), hands, feet, and congenital abnormality of the heart, ears, kidneys and genitalia. Bleeding due to platelet abnormalities and immunological defects are very common. The exact cause at the origin of partial loss of 11q is not fully understood. | Overview of Chromosome 11, Partial Monosomy 11q. Partial monosomy 11q syndrome is a rare chromosomal disorder in which a portion of the long arm of chromosome 11 is deleted (missing). Jacobsen syndrome is observed in SOME patients with 11q partial deletion. The region consistently missing in individuals with this disorder (JS) is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (this chromosome region is called the Jacobsen syndrome critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests (with or without the FISH staining technique), and CGH array.An 11q deletion involving regions ouside the JS crititcal region causes a different genetic condition.The range and severity of symptoms varies, greatly depending on the exact location and size of the missing genetic material. Symptoms commonly associated with partial monosomy 11q include abnormally slow growth before and after birth (prenatal and postnatal growth delay), moderate to severe delay in skills requiring coordination of mental and muscular activity and intellectual disability Most affected persons have mild to severe intellectual disability but rarely, individuals may have normal-borderline intelligence. Characteristic physical abnormalities may include short stature, unusual shape of the head and face (craniofacial dysmorphism), hands, feet, and congenital abnormality of the heart, ears, kidneys and genitalia. Bleeding due to platelet abnormalities and immunological defects are very common. The exact cause at the origin of partial loss of 11q is not fully understood. | 239 | Chromosome 11, Partial Monosomy 11q |
nord_239_1 | Symptoms of Chromosome 11, Partial Monosomy 11q | Symptoms and physical characteristics associated with partial monosomy 11q vary greatly depending on the exact size and gene content of the deleted material on chromosome 11. For a complete genetic assessment it is important that both traditional chromosome tests and CGH array are performed. No specific feature has been seen in every person, so it is important to note that affected children will not have all of the symptoms discussed below.Physical development: Many individuals with partial monosomy 11q would reach an adult height that is well below average (short stature). Some children with partial monosomy 11q may have low levels of a growth hormone known as insulin growth factor-1 (IGF-1) and may have very short stature.Intellectual development: Affected infants and children may experience delays in reaching developmental milestones (psychomotor developmental delay) and behavioral problems. Rarely, intelligence may be borderline-normal, but in most children have mild to moderate intellectual disability. Affected infants may also have severe speech impairment. The degree of speech impairment and intellectual disability are usually associated with larger deletions. Individuals with smaller deleted segments are more likely to have borderline intelligence and less severe symptoms overall. About a half of affected individuals haves autism or autistic behaviour.A specific finding frequently associated with partial monosomy 11q (85% of cases) is thrombocytopenia, a condition characterized by a reduced number of platelets. Normal platelets are tiny, specialized blood cells that, in case of vascular damage, help prevent bleeding by forming clots. When a blood vessel is injured, platelets travel to the site of injury and clump together to form a clot that stops bleeding. Infants with partial monosomy 11q very frequently have a low number of platelets which causes them to bruise easily and bleed excessively. They may be at risk of internal bleeding. As affected individuals age, platelet numbers usually increase, but many individuals still bruise easily and experience prolonged bleeding episodes suggesting that the platelets are not functioning properly.The bleeding abnormalities associated with partial monosomy 11q are extremely similar to a bleeding disorder called Paris-Trousseau syndrome (PTS). Some researchers believe these disorders are actually one disorder; some believe PTS is a variant of partial monosomy 11q; and others believe that they are similar, yet distinct, disorders. Virtually all children with Jacobsen syndrome have thrombocytopenia/thrombocytopathia, and it is extremely important to assume that platelet functions may be impaired even when their number is normal. Blood or platelet transfusion must be considered before and during surgery.Another common disorder in patients with 11q deletion is immunodeficiency with a deficit of cellular and/or humoral immunity. As a consequence, children with JS have frequent infections of ears, respiratory tract, skin, etc and may not produce enough antibodies after vaccinations.Many infants with partial monosomy 11q exhibit distinctive facial features including skull deformities (macrocrania or abnormal skull shape caused by craniosynostosis), high prominent forehead, facial asymmetry, widely spaced eyes (hypertelorism), crossed eyes (strabismus), drooping eyelids (palpebral ptosis) and the presence of tiny folds of skin on either side of the nose that may partially cover the eyes’ inner corners near the nose (epicanthal folds). The nasal bridge is broad and the nose is short; nostrils that are flared forward (anteverted nares); thin upper lips; down-turned mouth; small lower jaw (micrognathia); low-set and small malformed (dysplastic) ears. Children have small baby teeth but permanent teeth are usually large and some individuals may develop dental abnormalities. Infants with partial monosomy 11q may also have abnormalities of the hands and feet: minor webbing of the fingers (skin syndactyly); thin fingers; abnormal curving of the pinky so that is bent toward the ring finger (clinodactyly); the presence of a single crease across the palms of the hands (simian crease); big and long allux with short toes; an abnormally twisted position of feet (talipes equinovarus or clubfoot). In addition, in many children, certain joints may become fixed or stuck in a bent position (contractures). A contracture occurs when thickening and shortening of tissue such as muscle fibers causes deformity and restricts movements of affected areas, especially the joints. Scoliosis (abnormal curve of the spine) may develop during adolescence.More than half of individuals with partial monosomy 11q show heart abnormalities that are present at birth (congenital heart defects). The most common congenital heart defects associated with partial monosomy 11q are ventricular septal defects (VSDs) and left-sided obstructive lesions. The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, is the main vessel of arterial circulation, and carries blood from the left ventricle and away from the heart.Ventricular septal defects (VSDs) can occur in any portion of the ventricular septum. The size and location of the defect determine the severity of the symptoms. Small ventricular septal defects may close without treatment (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive cardiac failure). Symptoms associated with cardiac failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, unusually fast heartbeat (tachycardia) and/or failure to grow at the expected rate (failure to thrive). Large ventricular septal defects can cause life-threatening complications during infancy. Persistent elevation of the pressure within the artery that carries blood away from the heart and to the lungs (pulmonary artery) can cause permanent damage to the lungs.Left-sided obstructive lesions are defects that prevent the adequate blood flow from the heart. Such defects that have been associated with partial monosomy 11q include narrowing of aorta (aortic coarctation); narrowing of the valve that connects the left ventricle to the aorta (aortic valve stenosis); narrowing of the valve of that connects the lower and upper left chamber of the heart (mitral valve stenosis) and hypoplastic left heart syndrome, a group of closely-related defects characterized by underdevelopment (hypoplasia) of the left side of the heart and associated structures.Additional heart defects that have been reported in some individuals with partial monosomy 11q include double outlet right ventricle, in which both the pulmonary artery and aorta connect to the right ventricle (the aorta normally connects to the left ventricle); transposition of the great arteries, in which the two large (great) arteries arise from the wrong area of the heart. The aorta arises from the right ventricle and the pulmonary arises from the left ventricle; aberrant right subclavian artery, in which one of the main arteries supplying blood to the upper arms and legs arises from the wrong area of the heart; and atrioventricular septal canal defects, in which the partitions (septa) and valves separating the right and left chambers of the heart are improperly developed.Cardiac abnormalities are usually present at birth, they can be very severe and require very early surgery in the neonatal period. However vascular stenosis (including aortic stenosis) may develop in some patients later in life. Individuals with partial monosomy 11q frequently have middle ear infections (otitis media) and inflammation of the sinuses (sinusitis). Some individuals with partial monosomy 11q experience some degree of hearing impairment.Additional findings have been associated with partial monosomy 11q. These finding affect less than half of affected individuals. In some cases, the fibrous joints (metopic sutures) between the two sides of the bone in the forehead (frontal bone) may close prematurely (craniosynostosis). As a result, the head may have an unusual appearance with an abnormally prominent forehead “triangular-shaped head when looked from above” (trigonocephaly). If craniosynostosis compromises the growth of the skull, there is indication for a early skull surgery (craniotomy), that would allow the head to develop.Additional findings affecting the eyes may occur including absence of some tissue from the colored portion of the eye (iris coloboma), giving the eye a “keyhole” appearance and improper developed of the nerve-rich membrane lining the eyes (retina). The retina converts visual images into nerves, which are then relayed to the brain. In some individuals with partial monosomy 11q a condition called tortuosity of the retinal vessels may occur. In this condition, the tiny vessels that supply blood to the retina may be twisted and malformed.Eczema, a skin condition in which individuals develop an inflamed, scaly, red rash that is often itchy, may also occur. Due to the immune defect, the skin can develop bacterial, viral (wart) and or fungal infections. After an injury, the scar may develop abnormally below the normal layer of skin tissue (atrophic scars) or, conversely, there may be enlarged, raised scars called keloids.Some individuals may develop gastrointestinal problems at birth including feeding difficulties, abnormal narrowing (stenosis) of the band of muscle fibers (pyloric sphincter) at the junction between the stomach and small intestine (pyloric stenosis), resulting in obstruction of the normal flow of stomach contents into the small intestine. Pyloric stenosis can cause affected individuals to vomit forcefully and may result in dehydration, a problem that is observed in the neonatal period. Surgical treatment of pyloric stenosis may be necessary. Children with Jacobsen syndrome often suffer from chronic constipation that would benefit from oral administration of edible oil.Some affected infants may also have abnormalities of the genital and urinary (genitourinary) systems. For example, females may have an abnormal passage between the bladder and the vagina (vescicovaginal fistula) (rare). In affected males, the urinary opening (meatus) may appear on the underside of the penis (hypospadias); the testes may fail to descend into the scrotum (cryptorchidism); and/or portions of the large intestine may protrude through an abnormal opening in muscles of the groin (inguinal hernia).Some infants with partial monosomy 11q may also have kidney (renal) abnormalities such as a horseshoe kidney (abnormally shaped kidneys) and duplicate kidney and/or a duplicate ureter, the small, thin tube that connects the kidneys to the bladder. The ureters drain urine through the muscular contractions. Most individuals in general population have two ureters (one connected to each kidney). A duplicate ureter is an extra ureter that may or may not be associated with any symptoms depending upon their exact location, whether they are malformed and whether they hinder the flow of urine. Kidney malformations are not always associated with obvious symptoms, but clinical problems may arise later in life, therefore an ultrasound scan of the abdomen is required to detect any kidney malformation and allow early monitoring of clinical conditions. | Symptoms of Chromosome 11, Partial Monosomy 11q. Symptoms and physical characteristics associated with partial monosomy 11q vary greatly depending on the exact size and gene content of the deleted material on chromosome 11. For a complete genetic assessment it is important that both traditional chromosome tests and CGH array are performed. No specific feature has been seen in every person, so it is important to note that affected children will not have all of the symptoms discussed below.Physical development: Many individuals with partial monosomy 11q would reach an adult height that is well below average (short stature). Some children with partial monosomy 11q may have low levels of a growth hormone known as insulin growth factor-1 (IGF-1) and may have very short stature.Intellectual development: Affected infants and children may experience delays in reaching developmental milestones (psychomotor developmental delay) and behavioral problems. Rarely, intelligence may be borderline-normal, but in most children have mild to moderate intellectual disability. Affected infants may also have severe speech impairment. The degree of speech impairment and intellectual disability are usually associated with larger deletions. Individuals with smaller deleted segments are more likely to have borderline intelligence and less severe symptoms overall. About a half of affected individuals haves autism or autistic behaviour.A specific finding frequently associated with partial monosomy 11q (85% of cases) is thrombocytopenia, a condition characterized by a reduced number of platelets. Normal platelets are tiny, specialized blood cells that, in case of vascular damage, help prevent bleeding by forming clots. When a blood vessel is injured, platelets travel to the site of injury and clump together to form a clot that stops bleeding. Infants with partial monosomy 11q very frequently have a low number of platelets which causes them to bruise easily and bleed excessively. They may be at risk of internal bleeding. As affected individuals age, platelet numbers usually increase, but many individuals still bruise easily and experience prolonged bleeding episodes suggesting that the platelets are not functioning properly.The bleeding abnormalities associated with partial monosomy 11q are extremely similar to a bleeding disorder called Paris-Trousseau syndrome (PTS). Some researchers believe these disorders are actually one disorder; some believe PTS is a variant of partial monosomy 11q; and others believe that they are similar, yet distinct, disorders. Virtually all children with Jacobsen syndrome have thrombocytopenia/thrombocytopathia, and it is extremely important to assume that platelet functions may be impaired even when their number is normal. Blood or platelet transfusion must be considered before and during surgery.Another common disorder in patients with 11q deletion is immunodeficiency with a deficit of cellular and/or humoral immunity. As a consequence, children with JS have frequent infections of ears, respiratory tract, skin, etc and may not produce enough antibodies after vaccinations.Many infants with partial monosomy 11q exhibit distinctive facial features including skull deformities (macrocrania or abnormal skull shape caused by craniosynostosis), high prominent forehead, facial asymmetry, widely spaced eyes (hypertelorism), crossed eyes (strabismus), drooping eyelids (palpebral ptosis) and the presence of tiny folds of skin on either side of the nose that may partially cover the eyes’ inner corners near the nose (epicanthal folds). The nasal bridge is broad and the nose is short; nostrils that are flared forward (anteverted nares); thin upper lips; down-turned mouth; small lower jaw (micrognathia); low-set and small malformed (dysplastic) ears. Children have small baby teeth but permanent teeth are usually large and some individuals may develop dental abnormalities. Infants with partial monosomy 11q may also have abnormalities of the hands and feet: minor webbing of the fingers (skin syndactyly); thin fingers; abnormal curving of the pinky so that is bent toward the ring finger (clinodactyly); the presence of a single crease across the palms of the hands (simian crease); big and long allux with short toes; an abnormally twisted position of feet (talipes equinovarus or clubfoot). In addition, in many children, certain joints may become fixed or stuck in a bent position (contractures). A contracture occurs when thickening and shortening of tissue such as muscle fibers causes deformity and restricts movements of affected areas, especially the joints. Scoliosis (abnormal curve of the spine) may develop during adolescence.More than half of individuals with partial monosomy 11q show heart abnormalities that are present at birth (congenital heart defects). The most common congenital heart defects associated with partial monosomy 11q are ventricular septal defects (VSDs) and left-sided obstructive lesions. The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, is the main vessel of arterial circulation, and carries blood from the left ventricle and away from the heart.Ventricular septal defects (VSDs) can occur in any portion of the ventricular septum. The size and location of the defect determine the severity of the symptoms. Small ventricular septal defects may close without treatment (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive cardiac failure). Symptoms associated with cardiac failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, unusually fast heartbeat (tachycardia) and/or failure to grow at the expected rate (failure to thrive). Large ventricular septal defects can cause life-threatening complications during infancy. Persistent elevation of the pressure within the artery that carries blood away from the heart and to the lungs (pulmonary artery) can cause permanent damage to the lungs.Left-sided obstructive lesions are defects that prevent the adequate blood flow from the heart. Such defects that have been associated with partial monosomy 11q include narrowing of aorta (aortic coarctation); narrowing of the valve that connects the left ventricle to the aorta (aortic valve stenosis); narrowing of the valve of that connects the lower and upper left chamber of the heart (mitral valve stenosis) and hypoplastic left heart syndrome, a group of closely-related defects characterized by underdevelopment (hypoplasia) of the left side of the heart and associated structures.Additional heart defects that have been reported in some individuals with partial monosomy 11q include double outlet right ventricle, in which both the pulmonary artery and aorta connect to the right ventricle (the aorta normally connects to the left ventricle); transposition of the great arteries, in which the two large (great) arteries arise from the wrong area of the heart. The aorta arises from the right ventricle and the pulmonary arises from the left ventricle; aberrant right subclavian artery, in which one of the main arteries supplying blood to the upper arms and legs arises from the wrong area of the heart; and atrioventricular septal canal defects, in which the partitions (septa) and valves separating the right and left chambers of the heart are improperly developed.Cardiac abnormalities are usually present at birth, they can be very severe and require very early surgery in the neonatal period. However vascular stenosis (including aortic stenosis) may develop in some patients later in life. Individuals with partial monosomy 11q frequently have middle ear infections (otitis media) and inflammation of the sinuses (sinusitis). Some individuals with partial monosomy 11q experience some degree of hearing impairment.Additional findings have been associated with partial monosomy 11q. These finding affect less than half of affected individuals. In some cases, the fibrous joints (metopic sutures) between the two sides of the bone in the forehead (frontal bone) may close prematurely (craniosynostosis). As a result, the head may have an unusual appearance with an abnormally prominent forehead “triangular-shaped head when looked from above” (trigonocephaly). If craniosynostosis compromises the growth of the skull, there is indication for a early skull surgery (craniotomy), that would allow the head to develop.Additional findings affecting the eyes may occur including absence of some tissue from the colored portion of the eye (iris coloboma), giving the eye a “keyhole” appearance and improper developed of the nerve-rich membrane lining the eyes (retina). The retina converts visual images into nerves, which are then relayed to the brain. In some individuals with partial monosomy 11q a condition called tortuosity of the retinal vessels may occur. In this condition, the tiny vessels that supply blood to the retina may be twisted and malformed.Eczema, a skin condition in which individuals develop an inflamed, scaly, red rash that is often itchy, may also occur. Due to the immune defect, the skin can develop bacterial, viral (wart) and or fungal infections. After an injury, the scar may develop abnormally below the normal layer of skin tissue (atrophic scars) or, conversely, there may be enlarged, raised scars called keloids.Some individuals may develop gastrointestinal problems at birth including feeding difficulties, abnormal narrowing (stenosis) of the band of muscle fibers (pyloric sphincter) at the junction between the stomach and small intestine (pyloric stenosis), resulting in obstruction of the normal flow of stomach contents into the small intestine. Pyloric stenosis can cause affected individuals to vomit forcefully and may result in dehydration, a problem that is observed in the neonatal period. Surgical treatment of pyloric stenosis may be necessary. Children with Jacobsen syndrome often suffer from chronic constipation that would benefit from oral administration of edible oil.Some affected infants may also have abnormalities of the genital and urinary (genitourinary) systems. For example, females may have an abnormal passage between the bladder and the vagina (vescicovaginal fistula) (rare). In affected males, the urinary opening (meatus) may appear on the underside of the penis (hypospadias); the testes may fail to descend into the scrotum (cryptorchidism); and/or portions of the large intestine may protrude through an abnormal opening in muscles of the groin (inguinal hernia).Some infants with partial monosomy 11q may also have kidney (renal) abnormalities such as a horseshoe kidney (abnormally shaped kidneys) and duplicate kidney and/or a duplicate ureter, the small, thin tube that connects the kidneys to the bladder. The ureters drain urine through the muscular contractions. Most individuals in general population have two ureters (one connected to each kidney). A duplicate ureter is an extra ureter that may or may not be associated with any symptoms depending upon their exact location, whether they are malformed and whether they hinder the flow of urine. Kidney malformations are not always associated with obvious symptoms, but clinical problems may arise later in life, therefore an ultrasound scan of the abdomen is required to detect any kidney malformation and allow early monitoring of clinical conditions. | 239 | Chromosome 11, Partial Monosomy 11q |
nord_239_2 | Causes of Chromosome 11, Partial Monosomy 11q | Partial monosomy 11q is a rare disorder in which a portion of the long arm (q) of chromosome 11 is missing (deleted). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Each human cell has 46 chromosomes: 23 are derived from the father and 23 from the mother. Pairs of human chromosomes are numbered from 1 through 22, and the additional 23rd pair is that of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. When stained, chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The range and severity of symptoms associated with this disorder depend in part upon the exact length and location of the deleted portion of chromosome 11q. In general, if less of the chromosome is missing, there may be fewer symptoms; if more of the chromosome is deleted, there may be more symptoms. In individuals with partial monosomy 11q and Jacobsen syndrome, the deleted portion of 11q tends to begin within or slightly below band 11q23 (breakpoint) and extend toward the end or “terminal” portion of chromosome 11q (qter). The symptoms of partial monosomy 11q result from the deleted genes, that are normally present on the missing portion of chromosome 11. Researchers have suggested that the region consistently missing in individuals with the disorder is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (JS critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests and CGH array.An 11q deletion involving regions ouside the JS crititcal region causes a different genetic condition.The exact cause of the chromosomal alteration in partial monosomy 11q is not fully understood. The medical literature has indicated that most documented cases appear to be due to a spontaneous genetic change (mutation) that occurs for unknown reasons. It is usually sporadic: only one case in a family and both parents have normal chromosomes (de novo). Less frequently a deletion 11q is the result of gametic (ovum or sperm) formation in an individual who is carrier of a chromosomal balanced translocation. A translocation is balanced if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes (no part of chromosome is missing or additional). If a chromosomal rearrangement is balanced, it is usually harmless to the carrier. However, the carrier has a very high risk of forming abnormal gametes and therefore, abnormal chromosomal disorders in the offspring. In these families a number early miscarriages may occur. Furthermore in these cases, the clinical features of children may be influenced also by additional imbalances of other chromosomes than 11. Chromosomal testing and the use of the FISH banding technique can determine whether a parent has a balanced translocation, while, as already mentioned, array CGH would show normal results as the parental abnormality is balanced. In the families where a parent has a balanced translocation, the risk for unbalanced offspring is high and prenatal diagnosis is offered.More recently, however, researchers have speculated that inheritance of a rare, fragile site or sites on the long arm of chromosome 11 may play a role in causing the disorder in some cases. Such a fragile site (or “folate-sensitive fragile site”), designated “FRA11B”, has been linked to band 11q23.3. Inheritance of FRA11B and subsequent breakage at this site during early embryonic development may give rise to the disorder in some individuals. Reports have indicated that the mothers of some affected individuals have been carriers for FRA11B and that FRA11B has been the deletion breakpoint. In addition, based upon evidence that the 11q breakpoint is sometimes beyond (i.e., telomeric to) FRA11B, some researchers suggest that there may be other fragile sites within or below11q23.3 in addition to FRA11B. In reported cases with breakpoints telomeric to FRA11B, the deleted chromosome has been paternal in origin, indicating that the tendency for a certain breakpoint may differ based upon the parental origin of the deleted chromosome. In the families where a parent has a fragile site, prenatal diagnosis is suggested, however the recurrence of the deletion in the offspring is uncommon.Patients with Jacobsen syndrome who have children can transmit the deleted chromosome with a 50% risk. In the families where a parent has JS, prenatal diagnosis is offered.In most cases, of Jacobsen syndrome individuals have an altered chromosome 11q in every cell of the body. However, some individuals have a mix of cells, some cells with an altered chromosome 11q and some with normal chromosomes 11.This condition is termed mosaicism and is generally associated with less severe symptoms or even, with no symptoms at all. In fact if a person has very few cells with the 11q deletion, that person may appear clinically normal.Individuals with the mosaic form of 11q deletion can transmit the deleted chromosome to their offspring, but the risk is unpredictable. In the families where a parent has 11q deletion mosaicism, prenatal diagnosis is offered. Some researchers believe the FLI1 gene on the long arm of chromosome 11 plays a role in the development the bleeding complications (Paris-Trousseau syndrome) associated with partial monosomy 11q. The extra function and role of this gene is unknown. More research is necessary to identify the specific genes (and their functions) associated with the symptoms of partial monosomy 11q. | Causes of Chromosome 11, Partial Monosomy 11q. Partial monosomy 11q is a rare disorder in which a portion of the long arm (q) of chromosome 11 is missing (deleted). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Each human cell has 46 chromosomes: 23 are derived from the father and 23 from the mother. Pairs of human chromosomes are numbered from 1 through 22, and the additional 23rd pair is that of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. When stained, chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The range and severity of symptoms associated with this disorder depend in part upon the exact length and location of the deleted portion of chromosome 11q. In general, if less of the chromosome is missing, there may be fewer symptoms; if more of the chromosome is deleted, there may be more symptoms. In individuals with partial monosomy 11q and Jacobsen syndrome, the deleted portion of 11q tends to begin within or slightly below band 11q23 (breakpoint) and extend toward the end or “terminal” portion of chromosome 11q (qter). The symptoms of partial monosomy 11q result from the deleted genes, that are normally present on the missing portion of chromosome 11. Researchers have suggested that the region consistently missing in individuals with the disorder is band q24.1 (11q24.1) suggesting that the absence of this specific area is critical to developing the disorder (JS critical region). It is important to stress that a complete genetic assessment requires both traditional chromosome tests and CGH array.An 11q deletion involving regions ouside the JS crititcal region causes a different genetic condition.The exact cause of the chromosomal alteration in partial monosomy 11q is not fully understood. The medical literature has indicated that most documented cases appear to be due to a spontaneous genetic change (mutation) that occurs for unknown reasons. It is usually sporadic: only one case in a family and both parents have normal chromosomes (de novo). Less frequently a deletion 11q is the result of gametic (ovum or sperm) formation in an individual who is carrier of a chromosomal balanced translocation. A translocation is balanced if pieces of two or more chromosomes break off and trade places, creating an altered but balanced set of chromosomes (no part of chromosome is missing or additional). If a chromosomal rearrangement is balanced, it is usually harmless to the carrier. However, the carrier has a very high risk of forming abnormal gametes and therefore, abnormal chromosomal disorders in the offspring. In these families a number early miscarriages may occur. Furthermore in these cases, the clinical features of children may be influenced also by additional imbalances of other chromosomes than 11. Chromosomal testing and the use of the FISH banding technique can determine whether a parent has a balanced translocation, while, as already mentioned, array CGH would show normal results as the parental abnormality is balanced. In the families where a parent has a balanced translocation, the risk for unbalanced offspring is high and prenatal diagnosis is offered.More recently, however, researchers have speculated that inheritance of a rare, fragile site or sites on the long arm of chromosome 11 may play a role in causing the disorder in some cases. Such a fragile site (or “folate-sensitive fragile site”), designated “FRA11B”, has been linked to band 11q23.3. Inheritance of FRA11B and subsequent breakage at this site during early embryonic development may give rise to the disorder in some individuals. Reports have indicated that the mothers of some affected individuals have been carriers for FRA11B and that FRA11B has been the deletion breakpoint. In addition, based upon evidence that the 11q breakpoint is sometimes beyond (i.e., telomeric to) FRA11B, some researchers suggest that there may be other fragile sites within or below11q23.3 in addition to FRA11B. In reported cases with breakpoints telomeric to FRA11B, the deleted chromosome has been paternal in origin, indicating that the tendency for a certain breakpoint may differ based upon the parental origin of the deleted chromosome. In the families where a parent has a fragile site, prenatal diagnosis is suggested, however the recurrence of the deletion in the offspring is uncommon.Patients with Jacobsen syndrome who have children can transmit the deleted chromosome with a 50% risk. In the families where a parent has JS, prenatal diagnosis is offered.In most cases, of Jacobsen syndrome individuals have an altered chromosome 11q in every cell of the body. However, some individuals have a mix of cells, some cells with an altered chromosome 11q and some with normal chromosomes 11.This condition is termed mosaicism and is generally associated with less severe symptoms or even, with no symptoms at all. In fact if a person has very few cells with the 11q deletion, that person may appear clinically normal.Individuals with the mosaic form of 11q deletion can transmit the deleted chromosome to their offspring, but the risk is unpredictable. In the families where a parent has 11q deletion mosaicism, prenatal diagnosis is offered. Some researchers believe the FLI1 gene on the long arm of chromosome 11 plays a role in the development the bleeding complications (Paris-Trousseau syndrome) associated with partial monosomy 11q. The extra function and role of this gene is unknown. More research is necessary to identify the specific genes (and their functions) associated with the symptoms of partial monosomy 11q. | 239 | Chromosome 11, Partial Monosomy 11q |
nord_239_3 | Affects of Chromosome 11, Partial Monosomy 11q | Partial monosomy 11q is an extremely rare chromosomal disorder that is apparent at birth. The disorder was initially described in the medical literature in 1973. Since that time, more than 200 cases have been described in the medical literature. According to some sources, more females are affected than males. The prevalence has been estimated at 1/100,000 births. | Affects of Chromosome 11, Partial Monosomy 11q. Partial monosomy 11q is an extremely rare chromosomal disorder that is apparent at birth. The disorder was initially described in the medical literature in 1973. Since that time, more than 200 cases have been described in the medical literature. According to some sources, more females are affected than males. The prevalence has been estimated at 1/100,000 births. | 239 | Chromosome 11, Partial Monosomy 11q |
nord_239_4 | Related disorders of Chromosome 11, Partial Monosomy 11q | Symptoms of the following disorders can be similar to those of partial monosomy 11q. Comparisons may be useful for a differential diagnosis.Chromosome 11 ring is an extremely rare chromosomal disorder in which chromosome 11 breaks at both ends. The chromosomal ends then join together, forming a ring. Affected infants may exhibit abnormally slow growth; psychomotordelay and characteristic physical malformations. These may include abnormalities of the head and facial (craniofacial) area such as an abnormally small, wide head (microbrachycephaly); a short nose with a low, depressed nasal bridge; small, retracted jaws (microretrognathism); and/or low-set ears. Eye (ocular) abnormalities may also be present such as widely-spaced eyes (ocular hypertelorism) and/or crossed eyes (strabismus). Additional features may include a short neck, abnormally low levels of all circulating blood cells (pancytopenia), congenital heart defects and/or other physical abnormalities. Cafè au lait and achromic spots are observed in children with ring chromosome 11. The exact cause of chromosome 11 ring is not fully understood.Interstitial deletion 11q is a partial monosomy (deletion) 11q due to the occurrence of two breaks within the long arm of chromosome 11, and loss of the fragment in between them. Therefore there is loss of chromosome material from 11q, but the very terminal 11q region is not missing. In interstitial deletion 11q, the clinical picture of the patient depends on position of the breakpoints and the size of the missing fragment. Sometimes the physical findings are similar to that of Jacobsen syndrome, when it involves in part the same chromosome region, more often the breaks are more proximal (higher up within chromosome 11q, closer to the centromere) and in this case the picture is usually different. Some degree of intellectual disability, physical growth delay, facial manifestation and organ malformation are usually present.Several different chromosomal disorders may be characterized by symptoms and physical findings that are similar to those associated with partial monosomy 11q. (For more information on chromosomal disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database). | Related disorders of Chromosome 11, Partial Monosomy 11q. Symptoms of the following disorders can be similar to those of partial monosomy 11q. Comparisons may be useful for a differential diagnosis.Chromosome 11 ring is an extremely rare chromosomal disorder in which chromosome 11 breaks at both ends. The chromosomal ends then join together, forming a ring. Affected infants may exhibit abnormally slow growth; psychomotordelay and characteristic physical malformations. These may include abnormalities of the head and facial (craniofacial) area such as an abnormally small, wide head (microbrachycephaly); a short nose with a low, depressed nasal bridge; small, retracted jaws (microretrognathism); and/or low-set ears. Eye (ocular) abnormalities may also be present such as widely-spaced eyes (ocular hypertelorism) and/or crossed eyes (strabismus). Additional features may include a short neck, abnormally low levels of all circulating blood cells (pancytopenia), congenital heart defects and/or other physical abnormalities. Cafè au lait and achromic spots are observed in children with ring chromosome 11. The exact cause of chromosome 11 ring is not fully understood.Interstitial deletion 11q is a partial monosomy (deletion) 11q due to the occurrence of two breaks within the long arm of chromosome 11, and loss of the fragment in between them. Therefore there is loss of chromosome material from 11q, but the very terminal 11q region is not missing. In interstitial deletion 11q, the clinical picture of the patient depends on position of the breakpoints and the size of the missing fragment. Sometimes the physical findings are similar to that of Jacobsen syndrome, when it involves in part the same chromosome region, more often the breaks are more proximal (higher up within chromosome 11q, closer to the centromere) and in this case the picture is usually different. Some degree of intellectual disability, physical growth delay, facial manifestation and organ malformation are usually present.Several different chromosomal disorders may be characterized by symptoms and physical findings that are similar to those associated with partial monosomy 11q. (For more information on chromosomal disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database). | 239 | Chromosome 11, Partial Monosomy 11q |
nord_239_5 | Diagnosis of Chromosome 11, Partial Monosomy 11q | Partial monosomy 11q may be diagnosed based upon a thorough clinical evaluation, the identification of characteristic physical findings, including low platelets and chromosomal studies and/or array comparative genomic hybridization (CGH) studies that demonstrate missing (deleted) material on chromosome 11q. Chromosome studies can be done on a blood sample. Chromosomes are analyzed after a laboratory procedure that includes a culture of cells obtained from a small amount of blood, and staining procedures. These chromosomes are stained so that they can be viewed more easily and are then examined under a microscope where the missing segment of chromosome 11q can be detected (high resolution karyotype). To determine the precise breakpoint on 11q, more a sensitive test may be necessary such as: fluorescent in situ hybridization (FISH), a diagnostic test in which probes marked by a specific color of fluorescent dye attach to a specific chromosome allowing researchers to better view that specific region of a chromosome.Array CGH is a method in which a normal DNA is mixed with patient’s DNA to detect gains (duplications) or losses (deletions) of chromosomal regions. Array CGH allows a very precise definition of breakpoints in the 11q deletion, and would allow detection of even very small imbalances, which, due to their size, cannot be detected by traditional chromosome studies. Array CGH would also detect any additional imbalances, if present, but it cannot detect any balanced rearrangement (such as a parental balanced translocation). A balanced translocation can only be diagnosed by a chromosome analysis and the FISH staining technique, if present in one parent or sibling of the affected child.).In some children, the diagnosis of partial monosomy 11q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may show a partial monosomy of chromosome 11q, especially when the test is performed because of a specific indication (one parent is affected with Jacobsen syndrome /one parent has the mosaic form of JS/one parent has a balanced translocation involving 11q/ one parent has a fragile site). In some cases this chromosome abnormality has been missed using standard chromosome tests only, but not when array CGH is performed.Prenatal cell-free DNA screening (NIPT= non invasive prenatal test) is a test that is performed from a sample of maternal blood. The test examines fetal DNA in the maternal bloodstream. However it is not a diagnostic test.A diagnostic test is a highly sensitive and specific test indicated to detect a condition on a population at risk, a screening test is indicated for general population without a specific risk, it must be clear that false positive and false negative results may be reported in a screening test. Therefore in case of a positive screening test a diagnostic test is usually required. The diagnosis of clinical abnormalities that may occur in association with partial monosomy 11q must be confirmed by clinical observation and specialized imaging studies and/or additional tests. For example, congenital heart defects may be confirmed by a thorough clinical examination and specialized tests that allow physicians to evaluate the structure and function of the heart. These tests may include X-ray studies, electrocardiogram (EKG), echocardiogram, and cardiac catheterization. X-ray studies may reveal abnormal enlargement of the heart (cardiomegaly) or malformation of other heart structures. An EKG, which records the heart’s electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, ultrasonic waves are directed toward the heart, enabling physicians to study cardiac function and motion. During cardiac catheterization, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart, measure the pressure within the heart, and/or thoroughly identify anatomical abnormalities. | Diagnosis of Chromosome 11, Partial Monosomy 11q. Partial monosomy 11q may be diagnosed based upon a thorough clinical evaluation, the identification of characteristic physical findings, including low platelets and chromosomal studies and/or array comparative genomic hybridization (CGH) studies that demonstrate missing (deleted) material on chromosome 11q. Chromosome studies can be done on a blood sample. Chromosomes are analyzed after a laboratory procedure that includes a culture of cells obtained from a small amount of blood, and staining procedures. These chromosomes are stained so that they can be viewed more easily and are then examined under a microscope where the missing segment of chromosome 11q can be detected (high resolution karyotype). To determine the precise breakpoint on 11q, more a sensitive test may be necessary such as: fluorescent in situ hybridization (FISH), a diagnostic test in which probes marked by a specific color of fluorescent dye attach to a specific chromosome allowing researchers to better view that specific region of a chromosome.Array CGH is a method in which a normal DNA is mixed with patient’s DNA to detect gains (duplications) or losses (deletions) of chromosomal regions. Array CGH allows a very precise definition of breakpoints in the 11q deletion, and would allow detection of even very small imbalances, which, due to their size, cannot be detected by traditional chromosome studies. Array CGH would also detect any additional imbalances, if present, but it cannot detect any balanced rearrangement (such as a parental balanced translocation). A balanced translocation can only be diagnosed by a chromosome analysis and the FISH staining technique, if present in one parent or sibling of the affected child.).In some children, the diagnosis of partial monosomy 11q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may show a partial monosomy of chromosome 11q, especially when the test is performed because of a specific indication (one parent is affected with Jacobsen syndrome /one parent has the mosaic form of JS/one parent has a balanced translocation involving 11q/ one parent has a fragile site). In some cases this chromosome abnormality has been missed using standard chromosome tests only, but not when array CGH is performed.Prenatal cell-free DNA screening (NIPT= non invasive prenatal test) is a test that is performed from a sample of maternal blood. The test examines fetal DNA in the maternal bloodstream. However it is not a diagnostic test.A diagnostic test is a highly sensitive and specific test indicated to detect a condition on a population at risk, a screening test is indicated for general population without a specific risk, it must be clear that false positive and false negative results may be reported in a screening test. Therefore in case of a positive screening test a diagnostic test is usually required. The diagnosis of clinical abnormalities that may occur in association with partial monosomy 11q must be confirmed by clinical observation and specialized imaging studies and/or additional tests. For example, congenital heart defects may be confirmed by a thorough clinical examination and specialized tests that allow physicians to evaluate the structure and function of the heart. These tests may include X-ray studies, electrocardiogram (EKG), echocardiogram, and cardiac catheterization. X-ray studies may reveal abnormal enlargement of the heart (cardiomegaly) or malformation of other heart structures. An EKG, which records the heart’s electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, ultrasonic waves are directed toward the heart, enabling physicians to study cardiac function and motion. During cardiac catheterization, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart, measure the pressure within the heart, and/or thoroughly identify anatomical abnormalities. | 239 | Chromosome 11, Partial Monosomy 11q |
nord_239_6 | Therapies of Chromosome 11, Partial Monosomy 11q | Treatment
The treatment of partial monosomy 11q is directed toward the specific symptoms that are apparent in each individual. Treatment usually requires the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, hematologists, immunologists, ear, nose and throat specialists, dental specialists, speech pathologists, specialists who assess and treat eye problems (ophthalmologists), specialists who assess and treat disorders affecting the hormones and glands (endocrinologists), specialists who assess and treat disorders of the skeleton (orthopedists) and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Physicians must regularly monitor affected individuals who tend to exhibit low platelet counts (thrombocytopenia) to ensure proper preventive measures and early, prompt treatment.Some affected individuals may be treated with platelet transfusion or desmopressin acetate, a drug that helps the blood clot. Blood or Platelet transfusion may be necessary before or during surgeries.In practice: It must be assumed that ALL patients with JS have a specific bleeding disorder called Paris-Trousseau syndrome. Paris-Trousseau has two components:1) Severe thrombocytopenia (low platelet count) of the newborn, which usually returns to near- or low-normal platelet counts during childhood
2) Persistent platelet dysfunctionIt should be assumed that all patients with JS are at risk for potentially life-threatening bleeding, especially in case of traumas or major surgeries. Medications that impair normal platelet function (e.g., ibuprofen, aspirin) should always be avoided. Desmopressin (DDAVP) IV or nasal spray may improve platelet aggregation during dental procedures, in case of mouth or nose bleeding. Oral contraceptives are indicated for females with heavy periods.Platelet or full blood transfusion may be needed for serious bleeding or before and during major surgeriesPatients with JS should have a complete blood count monthly for the first 3 months, then once per year. Platelet function studies should be done once the platelet count normalizes.Assume that JS patients are at risk for severe bleeding even in case of apparently normal platelet count and function.In many children, treatment would include surgical repair of certain malformations. For example, surgery may be performed to correct certain cardiac, craniofacial, ocular, skeletal, genitourinary, renal and/or other malformations that may be associated with this disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.For example, in affected children with craniosynostosis and trigonocephaly, surgery may be performed to help correct the premature closure of bones in the skull. In addition, certain congenital heart abnormalities occurring in association with partial monosomy 11q (e.g., ventricular septal defects) may be corrected surgically. Complications of certain congenital heart defects (e.g., rapid heartbeat [tachycardia], fluid accumulation, etc.) may be treated with a variety of drugs such as those that may help prevent or correct abnormal heart rhythms (antiarrhythmics) and/or medications that help to eliminate excessive fluid from the body (diuretics).In addition, nutritional considerations may be important in infants with VSDs, ASDs, and/or certain other congenital heart defects. Respiratory infections should be treated vigorously and early. Because of the risk of bacterial infection of the lining of the heart (endocarditis) and the heart valves, individuals with VSDs, ASDs, and/or certain other heart defects may be given antibiotic drugs before any surgical procedure, including dental procedures such as tooth extractions.In affected children with eye abnormalities (e.g., iris colobomas, strabismus, ptosis etc.), surgery and/or other measures may be used to help treat and/or correct such malformations. Corrective glasses, contact lenses, surgery, and/or other measures may also be used to help improve visual problems associated with such ocular abnormalities.In some children, abnormalities involving the joints, tendons, muscles, and bones (orthopedic), such as flexion contractures, scoliosis, clubfeet, and/or other abnormalities of the hands and/or feet may be treated by orthopedic techniques, potentially in combination with surgery. Again, the procedures used will depend upon the severity and location of the abnormalities and their associated symptoms. Physical therapy may also be prescribed to help improve coordination of certain movements (mobility).Early intervention is important in ensuring that children with partial monosomy 11q reach their highest potential. Services that may be beneficial may include special remedial education and other medical, social and/or vocational services. Genetic counseling is recommended for affected individuals and their families.Immunological issuePeople with Jacobsen syndrome are at significantly increased risk for having an impaired immune system, i.e. immunodeficiency, which can lead to life-threatening infection, and/or more frequent less serious infections. The type and severity of immunodeficiency is highly variable. Types of immunodeficiency that have been identified in people with JS: 1. common variable immune deficiency
2. hypogammaglobinemia
3. T-cell lymphopenia (including severe T-cell lymphopenia)
4. combined (B and T cell) immunodeficiency Testing is recommended for all people with Jacobsen syndrome. • Newborns should have T cells measured soon after birth
• At age 4-6 months, measure Immunoglobulins (IgG, IgA, IgM)
• At age 12 months, measure antibody titers for routine vaccinations such as tetanus and diphtheria
• At 2 years, consider administration of Pneumovax (23 valent pneumococcal polysaccharide vaccine) and measurement of post vaccination titers. This helps to identify patients who may lack the ability to mount appropriate immune responses. Using this vaccine has the additional benefit of enhancing protection to Streptococcus pneumoniae in immunocompetent patients. Older children and adults with JS and a pattern of recurrent infections should be evaluated for the presence of immunodeficiency with similar testing as described above. Consultation with an allergist/immunologist familiar with the evaluation and treatment of patients with immunodeficiency may facilitate diagnosis. Abnormal screening tests, concern for immune deficiency or recognition of a pattern of recurrent infections should prompt earlier evaluation, treatment and referral to an immunologist. Recommendations based on what is known to date regarding immunodeficiency in JS: • Routine vaccinations and COVID vaccine should be given unless there is a known T cell deficiency
• Pneumovax-23 at approximately 2 years of age or in older patients with recurrent infections being evaluated for immunodeficiency
• Early treatment of infections with antibiotics
• Repeat immunologic evaluation if infections are recurrent or severe (even if tests were normal the first time)
• Synagis (to prevent RSV infection) should be strongly considered in children less than 2 years with recurrent respiratory symptoms or any immunologic abnormality, even in the absence of cardiac issues.
• Some patients with low T cell numbers may benefit from prophylactic antibiotics, especially if the T cell number is felt to increase their risk of opportunistic infections. ther patients with hypogammaglobulinemia and recurrent infections may also benefit from certain antibiotic regimens. Immunologists often prescribe prophylactic antibiotics in an attempt to reduce the frequency and severity of sinopulmonary infections caused by encapsulated organisms.
• The use of intravenous or subcutaneous immunoglobulin replacement for patients with JS should follow the current recommendations for its use in patients with immunodeficiency. | Therapies of Chromosome 11, Partial Monosomy 11q. Treatment
The treatment of partial monosomy 11q is directed toward the specific symptoms that are apparent in each individual. Treatment usually requires the coordinated efforts of a team of specialists. Pediatricians, surgeons, cardiologists, hematologists, immunologists, ear, nose and throat specialists, dental specialists, speech pathologists, specialists who assess and treat eye problems (ophthalmologists), specialists who assess and treat disorders affecting the hormones and glands (endocrinologists), specialists who assess and treat disorders of the skeleton (orthopedists) and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.Physicians must regularly monitor affected individuals who tend to exhibit low platelet counts (thrombocytopenia) to ensure proper preventive measures and early, prompt treatment.Some affected individuals may be treated with platelet transfusion or desmopressin acetate, a drug that helps the blood clot. Blood or Platelet transfusion may be necessary before or during surgeries.In practice: It must be assumed that ALL patients with JS have a specific bleeding disorder called Paris-Trousseau syndrome. Paris-Trousseau has two components:1) Severe thrombocytopenia (low platelet count) of the newborn, which usually returns to near- or low-normal platelet counts during childhood
2) Persistent platelet dysfunctionIt should be assumed that all patients with JS are at risk for potentially life-threatening bleeding, especially in case of traumas or major surgeries. Medications that impair normal platelet function (e.g., ibuprofen, aspirin) should always be avoided. Desmopressin (DDAVP) IV or nasal spray may improve platelet aggregation during dental procedures, in case of mouth or nose bleeding. Oral contraceptives are indicated for females with heavy periods.Platelet or full blood transfusion may be needed for serious bleeding or before and during major surgeriesPatients with JS should have a complete blood count monthly for the first 3 months, then once per year. Platelet function studies should be done once the platelet count normalizes.Assume that JS patients are at risk for severe bleeding even in case of apparently normal platelet count and function.In many children, treatment would include surgical repair of certain malformations. For example, surgery may be performed to correct certain cardiac, craniofacial, ocular, skeletal, genitourinary, renal and/or other malformations that may be associated with this disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.For example, in affected children with craniosynostosis and trigonocephaly, surgery may be performed to help correct the premature closure of bones in the skull. In addition, certain congenital heart abnormalities occurring in association with partial monosomy 11q (e.g., ventricular septal defects) may be corrected surgically. Complications of certain congenital heart defects (e.g., rapid heartbeat [tachycardia], fluid accumulation, etc.) may be treated with a variety of drugs such as those that may help prevent or correct abnormal heart rhythms (antiarrhythmics) and/or medications that help to eliminate excessive fluid from the body (diuretics).In addition, nutritional considerations may be important in infants with VSDs, ASDs, and/or certain other congenital heart defects. Respiratory infections should be treated vigorously and early. Because of the risk of bacterial infection of the lining of the heart (endocarditis) and the heart valves, individuals with VSDs, ASDs, and/or certain other heart defects may be given antibiotic drugs before any surgical procedure, including dental procedures such as tooth extractions.In affected children with eye abnormalities (e.g., iris colobomas, strabismus, ptosis etc.), surgery and/or other measures may be used to help treat and/or correct such malformations. Corrective glasses, contact lenses, surgery, and/or other measures may also be used to help improve visual problems associated with such ocular abnormalities.In some children, abnormalities involving the joints, tendons, muscles, and bones (orthopedic), such as flexion contractures, scoliosis, clubfeet, and/or other abnormalities of the hands and/or feet may be treated by orthopedic techniques, potentially in combination with surgery. Again, the procedures used will depend upon the severity and location of the abnormalities and their associated symptoms. Physical therapy may also be prescribed to help improve coordination of certain movements (mobility).Early intervention is important in ensuring that children with partial monosomy 11q reach their highest potential. Services that may be beneficial may include special remedial education and other medical, social and/or vocational services. Genetic counseling is recommended for affected individuals and their families.Immunological issuePeople with Jacobsen syndrome are at significantly increased risk for having an impaired immune system, i.e. immunodeficiency, which can lead to life-threatening infection, and/or more frequent less serious infections. The type and severity of immunodeficiency is highly variable. Types of immunodeficiency that have been identified in people with JS: 1. common variable immune deficiency
2. hypogammaglobinemia
3. T-cell lymphopenia (including severe T-cell lymphopenia)
4. combined (B and T cell) immunodeficiency Testing is recommended for all people with Jacobsen syndrome. • Newborns should have T cells measured soon after birth
• At age 4-6 months, measure Immunoglobulins (IgG, IgA, IgM)
• At age 12 months, measure antibody titers for routine vaccinations such as tetanus and diphtheria
• At 2 years, consider administration of Pneumovax (23 valent pneumococcal polysaccharide vaccine) and measurement of post vaccination titers. This helps to identify patients who may lack the ability to mount appropriate immune responses. Using this vaccine has the additional benefit of enhancing protection to Streptococcus pneumoniae in immunocompetent patients. Older children and adults with JS and a pattern of recurrent infections should be evaluated for the presence of immunodeficiency with similar testing as described above. Consultation with an allergist/immunologist familiar with the evaluation and treatment of patients with immunodeficiency may facilitate diagnosis. Abnormal screening tests, concern for immune deficiency or recognition of a pattern of recurrent infections should prompt earlier evaluation, treatment and referral to an immunologist. Recommendations based on what is known to date regarding immunodeficiency in JS: • Routine vaccinations and COVID vaccine should be given unless there is a known T cell deficiency
• Pneumovax-23 at approximately 2 years of age or in older patients with recurrent infections being evaluated for immunodeficiency
• Early treatment of infections with antibiotics
• Repeat immunologic evaluation if infections are recurrent or severe (even if tests were normal the first time)
• Synagis (to prevent RSV infection) should be strongly considered in children less than 2 years with recurrent respiratory symptoms or any immunologic abnormality, even in the absence of cardiac issues.
• Some patients with low T cell numbers may benefit from prophylactic antibiotics, especially if the T cell number is felt to increase their risk of opportunistic infections. ther patients with hypogammaglobulinemia and recurrent infections may also benefit from certain antibiotic regimens. Immunologists often prescribe prophylactic antibiotics in an attempt to reduce the frequency and severity of sinopulmonary infections caused by encapsulated organisms.
• The use of intravenous or subcutaneous immunoglobulin replacement for patients with JS should follow the current recommendations for its use in patients with immunodeficiency. | 239 | Chromosome 11, Partial Monosomy 11q |
nord_240_0 | Overview of Chromosome 11, Partial Trisomy 11q | Chromosome 11, Partial Trisomy 11q is a rare chromosomal disorder in which the end (distal) portion of the long arm (q) of the 11th chromosome appears three times (trisomy) rather than twice in cells of the body. Although associated symptoms and findings may vary, the disorder is often associated with delayed growth before and after birth (prenatal and postnatal growth retardation); varying degrees of mental retardation; distinctive abnormalities of the skull and facial (craniofacial) region; and/or other features. Chromosomal analysis is necessary for a definite diagnosis. | Overview of Chromosome 11, Partial Trisomy 11q. Chromosome 11, Partial Trisomy 11q is a rare chromosomal disorder in which the end (distal) portion of the long arm (q) of the 11th chromosome appears three times (trisomy) rather than twice in cells of the body. Although associated symptoms and findings may vary, the disorder is often associated with delayed growth before and after birth (prenatal and postnatal growth retardation); varying degrees of mental retardation; distinctive abnormalities of the skull and facial (craniofacial) region; and/or other features. Chromosomal analysis is necessary for a definite diagnosis. | 240 | Chromosome 11, Partial Trisomy 11q |
nord_240_1 | Symptoms of Chromosome 11, Partial Trisomy 11q | Chromosome 11, Partial Trisomy 11q is commonly characterized by growth retardation before and after birth, delayed acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation), mild to moderate mental retardation, and distinctive craniofacial abnormalities. In individuals with Partial Trisomy 11q, craniofacial abnormalities may include an abnormally small head (microcephaly) that may appear unusually short and broad (brachycephaly); a short nose; low-set ears; and/or incomplete closure of the roof of the mouth (cleft palate) or a highly arched palate. Many affected individuals also have abnormal pits or depressions and/or outgrowths of skin and cartilage in front of the ears (preauricular pits or tags); a small jaw (micrognathia); a retracted lower lip; and/or an unusually long vertical groove in the center of the upper lip (philtrum). Additional craniofacial features may sometimes include widely spaced eyes (ocular hypertelorism); downwardly slanting eyelid folds (palpebral fissures); vertical skin folds over the eyes' inner corners (epicanthal folds); and/or abnormal deviation of one eye in relation to the other (strabismus). In addition, in some cases, one side of the face may appear smaller than or relatively dissimilar to the other (facial asymmetry). In some affected individuals, Chromosome 11, Partial Trisomy 11q may also be associated with additional physical findings. These may include skeletal abnormalities, such as malformation of the collarbone (clavicular defect) and/or dislocation or improper development (dysplasia) of the hips; structural malformations of the heart that are present at birth (congenital heart defects); and/or underdevelopment or absence of the band of nerve fibers that normally joins the two hemispheres of the brain (hypoplasia or agenesis of the corpus callosum). Additional abnormalities that have been reported in association with Partial Trisomy 11q have included an unusually short neck; abnormal looseness of the skin (cutis laxa); abnormal creases on the palms of the hands; or undescended testes (cryptorchidism) and/or an unusually small penis (micropenis) in affected males. | Symptoms of Chromosome 11, Partial Trisomy 11q. Chromosome 11, Partial Trisomy 11q is commonly characterized by growth retardation before and after birth, delayed acquisition of skills requiring the coordination of mental and motor activities (psychomotor retardation), mild to moderate mental retardation, and distinctive craniofacial abnormalities. In individuals with Partial Trisomy 11q, craniofacial abnormalities may include an abnormally small head (microcephaly) that may appear unusually short and broad (brachycephaly); a short nose; low-set ears; and/or incomplete closure of the roof of the mouth (cleft palate) or a highly arched palate. Many affected individuals also have abnormal pits or depressions and/or outgrowths of skin and cartilage in front of the ears (preauricular pits or tags); a small jaw (micrognathia); a retracted lower lip; and/or an unusually long vertical groove in the center of the upper lip (philtrum). Additional craniofacial features may sometimes include widely spaced eyes (ocular hypertelorism); downwardly slanting eyelid folds (palpebral fissures); vertical skin folds over the eyes' inner corners (epicanthal folds); and/or abnormal deviation of one eye in relation to the other (strabismus). In addition, in some cases, one side of the face may appear smaller than or relatively dissimilar to the other (facial asymmetry). In some affected individuals, Chromosome 11, Partial Trisomy 11q may also be associated with additional physical findings. These may include skeletal abnormalities, such as malformation of the collarbone (clavicular defect) and/or dislocation or improper development (dysplasia) of the hips; structural malformations of the heart that are present at birth (congenital heart defects); and/or underdevelopment or absence of the band of nerve fibers that normally joins the two hemispheres of the brain (hypoplasia or agenesis of the corpus callosum). Additional abnormalities that have been reported in association with Partial Trisomy 11q have included an unusually short neck; abnormal looseness of the skin (cutis laxa); abnormal creases on the palms of the hands; or undescended testes (cryptorchidism) and/or an unusually small penis (micropenis) in affected males. | 240 | Chromosome 11, Partial Trisomy 11q |
nord_240_2 | Causes of Chromosome 11, Partial Trisomy 11q | In individuals with Chromosome 11, Partial Trisomy 11q, the end (distal) region of the long arm (q) of chromosome 11 is present three times (i.e., trisomic or duplicated) rather than twice in cells of the body. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.Evidence suggests that Partial Trisomy 11q typically results from a translocation involving chromosome 11q and another chromosome, usually chromosome 22q. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. In individuals with Partial Trisomy 11q, such translocations most commonly appear to be transmitted by a parent who is a carrier of a “balanced” translocation. If a chromosomal rearrangement is balanced, meaning that it consists of an altered but balanced set of chromosomes, it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier's offspring. Chromosomal analysis may determine whether a parent has a balanced translocation. In a few cases, chromosomal rearrangements resulting in Partial Trisomy 11q have appeared to occur spontaneously for unknown reasons (de novo). In such cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. | Causes of Chromosome 11, Partial Trisomy 11q. In individuals with Chromosome 11, Partial Trisomy 11q, the end (distal) region of the long arm (q) of chromosome 11 is present three times (i.e., trisomic or duplicated) rather than twice in cells of the body. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.Evidence suggests that Partial Trisomy 11q typically results from a translocation involving chromosome 11q and another chromosome, usually chromosome 22q. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. In individuals with Partial Trisomy 11q, such translocations most commonly appear to be transmitted by a parent who is a carrier of a “balanced” translocation. If a chromosomal rearrangement is balanced, meaning that it consists of an altered but balanced set of chromosomes, it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier's offspring. Chromosomal analysis may determine whether a parent has a balanced translocation. In a few cases, chromosomal rearrangements resulting in Partial Trisomy 11q have appeared to occur spontaneously for unknown reasons (de novo). In such cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. | 240 | Chromosome 11, Partial Trisomy 11q |
nord_240_3 | Affects of Chromosome 11, Partial Trisomy 11q | Chromosome 11, Partial Trisomy 11q is a very rare chromosomal disorder that is reported to affect more females than males. Approximately 45 cases of this disorder have been documented in the medical literature. | Affects of Chromosome 11, Partial Trisomy 11q. Chromosome 11, Partial Trisomy 11q is a very rare chromosomal disorder that is reported to affect more females than males. Approximately 45 cases of this disorder have been documented in the medical literature. | 240 | Chromosome 11, Partial Trisomy 11q |
nord_240_4 | Related disorders of Chromosome 11, Partial Trisomy 11q | Symptoms of the following disorders can be similar to those of Chromosome 11, Partial Trisomy 11q. Comparisons may be useful for a differential diagnosis:Many chromosomal disorders have features similar to Chromosome 11, Partial Trisomy 11q. The only way to determine which chromosomal disorder an individual has is through genetic testing. (For more information on these disorders, choose “Chromosomal Disorder” as your search term in the Rare Disease Database.) | Related disorders of Chromosome 11, Partial Trisomy 11q. Symptoms of the following disorders can be similar to those of Chromosome 11, Partial Trisomy 11q. Comparisons may be useful for a differential diagnosis:Many chromosomal disorders have features similar to Chromosome 11, Partial Trisomy 11q. The only way to determine which chromosomal disorder an individual has is through genetic testing. (For more information on these disorders, choose “Chromosomal Disorder” as your search term in the Rare Disease Database.) | 240 | Chromosome 11, Partial Trisomy 11q |
nord_240_5 | Diagnosis of Chromosome 11, Partial Trisomy 11q | Chromosome 11, Partial Trisomy 11q may be diagnosed through genetic testing, either during pregnancy (prenatally) or after birth (postnatally). Prenatal procedures such as amniocentesis, chorionic villus sampling, and fetal blood sampling involve chromosomal analysis of fluid and/or tissue samples extracted from the fetus or the uterus during pregnancy (prenatally). | Diagnosis of Chromosome 11, Partial Trisomy 11q. Chromosome 11, Partial Trisomy 11q may be diagnosed through genetic testing, either during pregnancy (prenatally) or after birth (postnatally). Prenatal procedures such as amniocentesis, chorionic villus sampling, and fetal blood sampling involve chromosomal analysis of fluid and/or tissue samples extracted from the fetus or the uterus during pregnancy (prenatally). | 240 | Chromosome 11, Partial Trisomy 11q |
nord_240_6 | Therapies of Chromosome 11, Partial Trisomy 11q | TreatmentTreatment of Chromosome 11, Partial Trisomy 11q is symptomatic and supportive. Special education, physical therapy, and other medical, social, or vocational services are of benefit to the affected individual, and are often necessary for the child to reach his/her full potential. Genetic counseling will be of benefit for affected individuals and their families. | Therapies of Chromosome 11, Partial Trisomy 11q. TreatmentTreatment of Chromosome 11, Partial Trisomy 11q is symptomatic and supportive. Special education, physical therapy, and other medical, social, or vocational services are of benefit to the affected individual, and are often necessary for the child to reach his/her full potential. Genetic counseling will be of benefit for affected individuals and their families. | 240 | Chromosome 11, Partial Trisomy 11q |
nord_241_0 | Overview of Chromosome 13, Partial Monosomy 13q | Chromosome 13, Partial Monosomy 13q is a rare chromosomal disorder in which a portion of the long arm (q) of chromosome 13 is missing (deleted or monosomic). The range and severity of symptoms may vary greatly, depending upon the exact size and location of the deletion on 13q. Chromosome 13, Partial Monosomy 13q is usually apparent at birth and may be characterized by low birth weight, malformations of the head and facial (craniofacial) area, abnormalities of the eyes, defects of the hands and/or feet, genital malformations in affected males, and/or additional physical abnormalities. Affected infants and children may also exhibit delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation) as well as varying degrees of intellectual disability. In the majority of cases, Chromosome 13, Partial Monosomy 13q appears to occur randomly, for no apparent reason (sporadic). | Overview of Chromosome 13, Partial Monosomy 13q. Chromosome 13, Partial Monosomy 13q is a rare chromosomal disorder in which a portion of the long arm (q) of chromosome 13 is missing (deleted or monosomic). The range and severity of symptoms may vary greatly, depending upon the exact size and location of the deletion on 13q. Chromosome 13, Partial Monosomy 13q is usually apparent at birth and may be characterized by low birth weight, malformations of the head and facial (craniofacial) area, abnormalities of the eyes, defects of the hands and/or feet, genital malformations in affected males, and/or additional physical abnormalities. Affected infants and children may also exhibit delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation) as well as varying degrees of intellectual disability. In the majority of cases, Chromosome 13, Partial Monosomy 13q appears to occur randomly, for no apparent reason (sporadic). | 241 | Chromosome 13, Partial Monosomy 13q |
nord_241_1 | Symptoms of Chromosome 13, Partial Monosomy 13q | In Chromosome 13, Partial Monosomy 13q, a rare chromosomal disorder, a portion of the long arm (q) of chromosome 13 is missing (deleted). Symptoms and physical characteristics associated with the disorder may vary greatly, depending upon the exact size and location of the deletion (monosomy) on chromosome 13q.In many cases, infants with Chromosome 13, Partial Monosomy 13q have a low birth weight and may fail to grow at the expected rate (failure to thrive). Moderate to severe growth delays may continue during childhood, resulting in short stature. In addition, in most cases, affected individuals exhibit a severe delay in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation). Severe intellectual impairment is also present in most cases. However, in some affected individuals, the degree of intellectual disability may be mild or moderate.Many infants with Chromosome 13, Partial Monosomy 13q may exhibit characteristic abnormalities of the head and facial (craniofacial) area such as an unusually small head (microcephaly); a wide, flat nasal bridge; a small lower jaw (micrognathia) with an abnormally prominent upper jaw (maxilla); protruding front teeth (incisors), large, low-set ears; and/or a short neck with abnormal skin folds (webbing). In some cases, in addition to exhibiting microcephaly, some affected infants may experience premature closure (craniosynostosis) of the fibrous joints (metopic sutures) between the two sides of the bone in the forehead (frontal bone). As a result, the head may have an unusual “triangular-shaped” appearance with a prominent forehead (trigonocephaly). Affected children with trigonocephaly may be at risk for abnormal development of the forebrain (holoprosencephaly). (For more information on this condition, choose “Holoprosencephaly” as your search term in the Rare Disease Database.)In rare, severe cases, additional craniofacial abnormalities may include incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove in the upper lip (cleft lip). (For more information on these conditions, choose “Cleft Palate and Cleft Lip” as your search terms in the Rare Disease Database.)Many infants and children with Chromosome 13, Partial Monosomy 13q also exhibit various eye (ocular) abnormalities. These often include unusually small eyes (microphthalmia), widely spaced eyes (ocular hypertelorism), drooping of the upper eyelids (ptosis), and/or vertical skin folds on either side of the nose (epicanthal folds) that may partially cover the eyes’ inner corners. Affected individuals may also exhibit abnormal clouding of the lens of the eye (cataract) and/or the front (anterior), clear portion of the eye through which light passes (corneal opacity). In addition, some tissue from the colored portion of the eye (iris) may be absent (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other eye tissues (i.e., the choroid). Such eye abnormalities may result in varying degrees of visual impairment or, in some cases, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.In some cases, infants and children with Partial Monosomy 13q may also exhibit a malignant tumor of the retina (retinoblastoma), the nerve-rich membrane lining the eyes. In such cases, both eyes are usually affected (bilateral retinoblastoma). Symptoms associated with retinoblastoma may include the appearance of a whitish mass in the pupil area behind the lens of the eye (leukokoria or “cat’s eye reflex”), crossed eyes (strabismus), diminished vision or blindness, pain and redness, and/or an abnormal buildup of pressure of the fluid of the eye (secondary glaucoma).Some individuals with Chromosome 13, Partial Monosomy 13q may also have malformations of the hands and/or feet. These may include underdeveloped (hypoplastic) or absent thumbs; fifth fingers that are abnormally bent (clinodactyly), webbing or fusion of certain fingers (syndactyly), unusually short big toes; and/or feet that are twisted in an abnormal position (talipes equinovarus or clubfoot). In some cases, affected individuals may exhibit additional skeletal abnormalities. These may include malformations of the ribs, abnormalities of bones in the spinal column (vertebrae), and/or sideways curvature of the spine (scoliosis).In some cases, males with Chromosome 13, Partial Monosomy 13q may have genital abnormalities. For example, the urinary opening (meatus) may appear on the underside of the penis (hypospadias), and/or the testes may fail to descend into the scrotum (cryptorchidism). In some cases, the scrotum may be unusually small and/or abnormally divided into two sections (bifid scrotum); the penis may be unusually small (micropenis), and/or an abnormal passage may be present between the scrotum and the anus (perineal fistula). In rare cases, the anal opening may be absent or covered by a thin membrane, causing obstruction (anal atresia).In some severe cases, individuals with Chromosome 13, Partial Monosomy 13q may also exhibit abnormalities of certain internal organs including the heart, brain, intestines, and/or kidneys.In some cases, heart malformations may be associated with Partial Monosomy 13q including Atrial and Ventricular Septal Defects, which are rare heart defects that are present at birth (congenital). The normal heart has four chambers with two upper chambers known as atria. They are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers of the heart are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. A small opening between the two atria (foramen ovale) is present at birth. Shortly after birth, the atrial septum gradually closes and covers this opening. In infants with Atrial Septal Defects, the atrial septum may not close properly or may be malformed during fetal development. As a result, the opening between the atria persists long after it should be closed, causing an increase in the workload on the right side of the heart and excessive blood flow to the lungs.Most children with Atrial Septal Defects exhibit no symptoms. However, in some cases, associated symptoms may include abnormal thinness, mild growth delays, and an increased susceptibility to repeated respiratory infections. In rare cases, severely affected children may experience breathlessness, easy fatigability with exercise, and/or irregular heartbeats (arrhythmias).Ventricular Septal Defects are characterized by an abnormal opening in the fibrous partition separating the two ventricles (ventricular septum). The size and location of the defect determine the severity of the symptoms. Small Ventricular Septal Defects may close on their own (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive cardiac failure). Symptoms associated with cardiac failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), abnormal enlargement of the liver (hepatomegaly), and/or failure to thrive. Large Ventricular Septal Defects can cause life-threatening complications during infancy. Persistent elevation of the pressure within the artery that carries blood away from the heart and to the lungs (pulmonary artery) can cause permanent damage to the lungs.As mentioned above, affected infants with trigonocephaly may be at risk for abnormal development of the forebrain (holoprosencephaly). In some cases of Chromosome 13, Partial Monosomy 13q, additional brain abnormalities may be present such as absence (agenesis) of certain portions of the brain (e.g., rhinencephalon and/or corpus callosum), protrusion of membranes that surround the brain (meninges) through an abnormal opening in the skull (meningocele), and/or an abnormal accumulation of cerebrospinal fluid in the skull, causing increased pressure on the brain (hydrocephaly).In addition, some individuals with Partial Monosomy 13q may also have Hirschsprung’s Disease, a disorder in which absence of nerve fibers (ganglia) in the muscle wall of the colon prevents the muscles from working to push waste materials (feces) through the lower digestive tract (peristalsis) . As a result, feces accumulate abnormally in the involved portion of the colon, causing massive widening (dilatation) of the colon (megacolon), diarrhea, constipation, abdominal distention, nausea, periodic vomiting, and/or loss of appetite (anorexia). (For more information on this disorder, choose “Hirschsprung” as your search term in the Rare Disease Database.)In rare cases, some individuals with Partial Monosomy 13q may also exhibit kidney (renal) abnormalities. These may include underdevelopment (hypoplasia) or absence (agenesis) of a kidney. | Symptoms of Chromosome 13, Partial Monosomy 13q. In Chromosome 13, Partial Monosomy 13q, a rare chromosomal disorder, a portion of the long arm (q) of chromosome 13 is missing (deleted). Symptoms and physical characteristics associated with the disorder may vary greatly, depending upon the exact size and location of the deletion (monosomy) on chromosome 13q.In many cases, infants with Chromosome 13, Partial Monosomy 13q have a low birth weight and may fail to grow at the expected rate (failure to thrive). Moderate to severe growth delays may continue during childhood, resulting in short stature. In addition, in most cases, affected individuals exhibit a severe delay in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation). Severe intellectual impairment is also present in most cases. However, in some affected individuals, the degree of intellectual disability may be mild or moderate.Many infants with Chromosome 13, Partial Monosomy 13q may exhibit characteristic abnormalities of the head and facial (craniofacial) area such as an unusually small head (microcephaly); a wide, flat nasal bridge; a small lower jaw (micrognathia) with an abnormally prominent upper jaw (maxilla); protruding front teeth (incisors), large, low-set ears; and/or a short neck with abnormal skin folds (webbing). In some cases, in addition to exhibiting microcephaly, some affected infants may experience premature closure (craniosynostosis) of the fibrous joints (metopic sutures) between the two sides of the bone in the forehead (frontal bone). As a result, the head may have an unusual “triangular-shaped” appearance with a prominent forehead (trigonocephaly). Affected children with trigonocephaly may be at risk for abnormal development of the forebrain (holoprosencephaly). (For more information on this condition, choose “Holoprosencephaly” as your search term in the Rare Disease Database.)In rare, severe cases, additional craniofacial abnormalities may include incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove in the upper lip (cleft lip). (For more information on these conditions, choose “Cleft Palate and Cleft Lip” as your search terms in the Rare Disease Database.)Many infants and children with Chromosome 13, Partial Monosomy 13q also exhibit various eye (ocular) abnormalities. These often include unusually small eyes (microphthalmia), widely spaced eyes (ocular hypertelorism), drooping of the upper eyelids (ptosis), and/or vertical skin folds on either side of the nose (epicanthal folds) that may partially cover the eyes’ inner corners. Affected individuals may also exhibit abnormal clouding of the lens of the eye (cataract) and/or the front (anterior), clear portion of the eye through which light passes (corneal opacity). In addition, some tissue from the colored portion of the eye (iris) may be absent (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other eye tissues (i.e., the choroid). Such eye abnormalities may result in varying degrees of visual impairment or, in some cases, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.In some cases, infants and children with Partial Monosomy 13q may also exhibit a malignant tumor of the retina (retinoblastoma), the nerve-rich membrane lining the eyes. In such cases, both eyes are usually affected (bilateral retinoblastoma). Symptoms associated with retinoblastoma may include the appearance of a whitish mass in the pupil area behind the lens of the eye (leukokoria or “cat’s eye reflex”), crossed eyes (strabismus), diminished vision or blindness, pain and redness, and/or an abnormal buildup of pressure of the fluid of the eye (secondary glaucoma).Some individuals with Chromosome 13, Partial Monosomy 13q may also have malformations of the hands and/or feet. These may include underdeveloped (hypoplastic) or absent thumbs; fifth fingers that are abnormally bent (clinodactyly), webbing or fusion of certain fingers (syndactyly), unusually short big toes; and/or feet that are twisted in an abnormal position (talipes equinovarus or clubfoot). In some cases, affected individuals may exhibit additional skeletal abnormalities. These may include malformations of the ribs, abnormalities of bones in the spinal column (vertebrae), and/or sideways curvature of the spine (scoliosis).In some cases, males with Chromosome 13, Partial Monosomy 13q may have genital abnormalities. For example, the urinary opening (meatus) may appear on the underside of the penis (hypospadias), and/or the testes may fail to descend into the scrotum (cryptorchidism). In some cases, the scrotum may be unusually small and/or abnormally divided into two sections (bifid scrotum); the penis may be unusually small (micropenis), and/or an abnormal passage may be present between the scrotum and the anus (perineal fistula). In rare cases, the anal opening may be absent or covered by a thin membrane, causing obstruction (anal atresia).In some severe cases, individuals with Chromosome 13, Partial Monosomy 13q may also exhibit abnormalities of certain internal organs including the heart, brain, intestines, and/or kidneys.In some cases, heart malformations may be associated with Partial Monosomy 13q including Atrial and Ventricular Septal Defects, which are rare heart defects that are present at birth (congenital). The normal heart has four chambers with two upper chambers known as atria. They are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers of the heart are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. A small opening between the two atria (foramen ovale) is present at birth. Shortly after birth, the atrial septum gradually closes and covers this opening. In infants with Atrial Septal Defects, the atrial septum may not close properly or may be malformed during fetal development. As a result, the opening between the atria persists long after it should be closed, causing an increase in the workload on the right side of the heart and excessive blood flow to the lungs.Most children with Atrial Septal Defects exhibit no symptoms. However, in some cases, associated symptoms may include abnormal thinness, mild growth delays, and an increased susceptibility to repeated respiratory infections. In rare cases, severely affected children may experience breathlessness, easy fatigability with exercise, and/or irregular heartbeats (arrhythmias).Ventricular Septal Defects are characterized by an abnormal opening in the fibrous partition separating the two ventricles (ventricular septum). The size and location of the defect determine the severity of the symptoms. Small Ventricular Septal Defects may close on their own (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive cardiac failure). Symptoms associated with cardiac failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), abnormal enlargement of the liver (hepatomegaly), and/or failure to thrive. Large Ventricular Septal Defects can cause life-threatening complications during infancy. Persistent elevation of the pressure within the artery that carries blood away from the heart and to the lungs (pulmonary artery) can cause permanent damage to the lungs.As mentioned above, affected infants with trigonocephaly may be at risk for abnormal development of the forebrain (holoprosencephaly). In some cases of Chromosome 13, Partial Monosomy 13q, additional brain abnormalities may be present such as absence (agenesis) of certain portions of the brain (e.g., rhinencephalon and/or corpus callosum), protrusion of membranes that surround the brain (meninges) through an abnormal opening in the skull (meningocele), and/or an abnormal accumulation of cerebrospinal fluid in the skull, causing increased pressure on the brain (hydrocephaly).In addition, some individuals with Partial Monosomy 13q may also have Hirschsprung’s Disease, a disorder in which absence of nerve fibers (ganglia) in the muscle wall of the colon prevents the muscles from working to push waste materials (feces) through the lower digestive tract (peristalsis) . As a result, feces accumulate abnormally in the involved portion of the colon, causing massive widening (dilatation) of the colon (megacolon), diarrhea, constipation, abdominal distention, nausea, periodic vomiting, and/or loss of appetite (anorexia). (For more information on this disorder, choose “Hirschsprung” as your search term in the Rare Disease Database.)In rare cases, some individuals with Partial Monosomy 13q may also exhibit kidney (renal) abnormalities. These may include underdevelopment (hypoplasia) or absence (agenesis) of a kidney. | 241 | Chromosome 13, Partial Monosomy 13q |
nord_241_2 | Causes of Chromosome 13, Partial Monosomy 13q | Chromosome 13, Partial Monosomy 13q is a rare chromosomal abnormality in which a portion of the long arm (q) of chromosome 13 is missing (deleted). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. For example, “13q32” refers to band 32 on the long arm of chromosome 13.In cases of Partial Monosomy 13q, the deletion of a portion of chromosome 13q is responsible for the symptoms and findings that characterize this chromosomal disorder. The range and severity of associated abnormalities may depend upon the exact length and location of the deleted portion of chromosome 13q.Researchers have attempted to determine the specific symptoms and physical characteristics (phenotype) that may be associated with deletion of certain band locations on chromosome 13q. The medical literature suggests that proximal deletions that do not extend into band q32 appear to be associated with growth retardation, mild to moderate intellectual disability, and varying physical abnormalities. (“Proximal” indicates nearest the point of attachment, nearest the center, or proximity to the point of origin.) Those with involvement of band q14 have a risk for retinoblastoma (see below). In addition, evidence suggests that deletions involving a portion of band q32 may be associated with growth retardation, severe intellectual impairment, abnormalities of the hands and feet, brain malformations, eye abnormalities, and other major malformations. Individuals with deletions limited to the end portion of 13q beyond band q32 (i.e., distal deletions involving bands q33-q34) may have severe intellectual disability and, in some cases, craniofacial abnormalities. Many researchers have suggested that such distal deletions do not usually appear to be associated with major malformations. However, according to one report, a distal deletion was present in a male child with myelomeningocele, an abnormally small head (microcephaly), minor facial abnormalities, and other findings. Myelomeningocele is a developmental defect in which a sac containing a portion of the spinal cord, its protective membranes (meninges), and cerebrospinal fluid abnormally protrudes through a defect in the spinal (vertebral) column. Research is ongoing concerning specific band regions that may be critical in producing certain features potentially associated with 13q deletions.As mentioned above, for those individuals with retinoblastoma, researchers have determined that the chromosomal region consistently missing is a portion of band q14 (13q14). Based upon this finding, it is suspected that a gene or genes at this chromosomal location may play a role in fetal retinal development. However, it is important to note that not all individuals with a 13q14 deletion develop retinoblastoma. According to the medical literature, approximately 20 percent of those with a deletion involving band 13q14 have the malignancy.The exact cause of Chromosome 13, Partial Monosomy 13q is not fully understood. In most documented cases, Partial Monosomy 13q appears to be due to spontaneous (de novo) errors very early in embryonic development. In such cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. However, in other cases, Chromosome 13, Partial Monosomy 13q may be due to a parental chromosomal rearrangement. In some cases, the parental chromosomal rearrangement may be a “balanced translocation.” Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. A translocation is balanced if it consists of an altered but balanced set of chromosomes.In other cases, the parental chromosomal rearrangement may be an inversion or an insertion. An inversion occurs when a chromosome breaks in two places and the segment then rejoins the chromosome in the reverse order. An insertion occurs when a segment of one chromosome is inserted into a break that exists in another chromosome in a different chromosomal (nonhomologous) pair.If such chromosomal rearrangements are balanced, they are usually harmless to the carrier. However, they are sometimes associated with a higher risk of abnormal chromosomal development in the carrier’s offspring. Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude a chromosomal rearrangement in one of the parents. | Causes of Chromosome 13, Partial Monosomy 13q. Chromosome 13, Partial Monosomy 13q is a rare chromosomal abnormality in which a portion of the long arm (q) of chromosome 13 is missing (deleted). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. For example, “13q32” refers to band 32 on the long arm of chromosome 13.In cases of Partial Monosomy 13q, the deletion of a portion of chromosome 13q is responsible for the symptoms and findings that characterize this chromosomal disorder. The range and severity of associated abnormalities may depend upon the exact length and location of the deleted portion of chromosome 13q.Researchers have attempted to determine the specific symptoms and physical characteristics (phenotype) that may be associated with deletion of certain band locations on chromosome 13q. The medical literature suggests that proximal deletions that do not extend into band q32 appear to be associated with growth retardation, mild to moderate intellectual disability, and varying physical abnormalities. (“Proximal” indicates nearest the point of attachment, nearest the center, or proximity to the point of origin.) Those with involvement of band q14 have a risk for retinoblastoma (see below). In addition, evidence suggests that deletions involving a portion of band q32 may be associated with growth retardation, severe intellectual impairment, abnormalities of the hands and feet, brain malformations, eye abnormalities, and other major malformations. Individuals with deletions limited to the end portion of 13q beyond band q32 (i.e., distal deletions involving bands q33-q34) may have severe intellectual disability and, in some cases, craniofacial abnormalities. Many researchers have suggested that such distal deletions do not usually appear to be associated with major malformations. However, according to one report, a distal deletion was present in a male child with myelomeningocele, an abnormally small head (microcephaly), minor facial abnormalities, and other findings. Myelomeningocele is a developmental defect in which a sac containing a portion of the spinal cord, its protective membranes (meninges), and cerebrospinal fluid abnormally protrudes through a defect in the spinal (vertebral) column. Research is ongoing concerning specific band regions that may be critical in producing certain features potentially associated with 13q deletions.As mentioned above, for those individuals with retinoblastoma, researchers have determined that the chromosomal region consistently missing is a portion of band q14 (13q14). Based upon this finding, it is suspected that a gene or genes at this chromosomal location may play a role in fetal retinal development. However, it is important to note that not all individuals with a 13q14 deletion develop retinoblastoma. According to the medical literature, approximately 20 percent of those with a deletion involving band 13q14 have the malignancy.The exact cause of Chromosome 13, Partial Monosomy 13q is not fully understood. In most documented cases, Partial Monosomy 13q appears to be due to spontaneous (de novo) errors very early in embryonic development. In such cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. However, in other cases, Chromosome 13, Partial Monosomy 13q may be due to a parental chromosomal rearrangement. In some cases, the parental chromosomal rearrangement may be a “balanced translocation.” Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. A translocation is balanced if it consists of an altered but balanced set of chromosomes.In other cases, the parental chromosomal rearrangement may be an inversion or an insertion. An inversion occurs when a chromosome breaks in two places and the segment then rejoins the chromosome in the reverse order. An insertion occurs when a segment of one chromosome is inserted into a break that exists in another chromosome in a different chromosomal (nonhomologous) pair.If such chromosomal rearrangements are balanced, they are usually harmless to the carrier. However, they are sometimes associated with a higher risk of abnormal chromosomal development in the carrier’s offspring. Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude a chromosomal rearrangement in one of the parents. | 241 | Chromosome 13, Partial Monosomy 13q |
nord_241_3 | Affects of Chromosome 13, Partial Monosomy 13q | Chromosome 13, Partial Monosomy 13q appears to affect females slightly more frequently than males. Although rare, deletions involving chromosome 13q are among the most commonly observed monosomies. Since the disorder was originally reported in 1963, more than 125 cases have been recorded in the medical literature. | Affects of Chromosome 13, Partial Monosomy 13q. Chromosome 13, Partial Monosomy 13q appears to affect females slightly more frequently than males. Although rare, deletions involving chromosome 13q are among the most commonly observed monosomies. Since the disorder was originally reported in 1963, more than 125 cases have been recorded in the medical literature. | 241 | Chromosome 13, Partial Monosomy 13q |
nord_241_4 | Related disorders of Chromosome 13, Partial Monosomy 13q | Symptoms of the following disorders can be similar to those of Chromosome 13, Partial Monosomy 13q. Comparisons may be useful for a differential diagnosis:Chromosome 13 Ring is a rare chromosomal disorder in which chromosome 13 breaks at both ends (i.e., the ends of the long arm [13q] and the short arm [13p]). The chromosomal ends then join together, forming a ring. Affected infants often exhibit a low birth weight, growth deficiency, psychomotor retardation, and/or intellectual impairment. In addition, they may also have distinctive abnormalities of the head and facial (craniofacial) area such as an abnormally small head (microcephaly), a wide, flat nasal bridge, an unusually prominent upper jaw (maxilla); protruding front teeth (incisors), large, low-set ears, and/or other craniofacial malformations. In some cases, affected individuals may also exhibit abnormalities of the eyes, which may include retinoblastoma in some cases; genital malformations in males; trigonocephaly and/or brain malformations, skeletal abnormalities, congenital heart defects; and/or additional physical abnormalities. Most cases of Chromosome 13 Ring appear to be due to a spontaneous (de novo) genetic change (mutation) very early in embryonic development that occurs for unknown reasons (sporadic).C Syndrome is an extremely rare disorder characterized by a “triangular-shaped” head with an abnormally prominent forehead (trigonocephaly) due to premature closure of the fibrous joints between certain bones in the skull (craniosynostosis). Additional abnormalities of the head and facial (craniofacial) area may be present such as a short nose with a broad nasal bridge; vertical folds over the inner corners of the eyes (epicanthus); a deep groove on the roof of the mouth (palate); and/or low-set, malformed ears. Additional physical abnormalities may include crossed eyes (strabismus); joints that are dislocated or fixed in a permanently flexed position (joint contractures); and/or additional skeletal abnormalities. In some cases, affected individuals may exhibit genital malformations, congenital heart defects, and/or other physical abnormalities. Intellectual disability is also present. C Syndrome is thought to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “C Syndrome” as your search term in the Rare Disease Database.)Many other chromosomal disorders have features similar to Chromosome 13, Partial Monosomy 13q. The only way to determine which chromosomal disorder an individual has is through chromosomal testing. (For more information on these disorders, choose “Chromosome” as your search term in the Rare Disease Database.) | Related disorders of Chromosome 13, Partial Monosomy 13q. Symptoms of the following disorders can be similar to those of Chromosome 13, Partial Monosomy 13q. Comparisons may be useful for a differential diagnosis:Chromosome 13 Ring is a rare chromosomal disorder in which chromosome 13 breaks at both ends (i.e., the ends of the long arm [13q] and the short arm [13p]). The chromosomal ends then join together, forming a ring. Affected infants often exhibit a low birth weight, growth deficiency, psychomotor retardation, and/or intellectual impairment. In addition, they may also have distinctive abnormalities of the head and facial (craniofacial) area such as an abnormally small head (microcephaly), a wide, flat nasal bridge, an unusually prominent upper jaw (maxilla); protruding front teeth (incisors), large, low-set ears, and/or other craniofacial malformations. In some cases, affected individuals may also exhibit abnormalities of the eyes, which may include retinoblastoma in some cases; genital malformations in males; trigonocephaly and/or brain malformations, skeletal abnormalities, congenital heart defects; and/or additional physical abnormalities. Most cases of Chromosome 13 Ring appear to be due to a spontaneous (de novo) genetic change (mutation) very early in embryonic development that occurs for unknown reasons (sporadic).C Syndrome is an extremely rare disorder characterized by a “triangular-shaped” head with an abnormally prominent forehead (trigonocephaly) due to premature closure of the fibrous joints between certain bones in the skull (craniosynostosis). Additional abnormalities of the head and facial (craniofacial) area may be present such as a short nose with a broad nasal bridge; vertical folds over the inner corners of the eyes (epicanthus); a deep groove on the roof of the mouth (palate); and/or low-set, malformed ears. Additional physical abnormalities may include crossed eyes (strabismus); joints that are dislocated or fixed in a permanently flexed position (joint contractures); and/or additional skeletal abnormalities. In some cases, affected individuals may exhibit genital malformations, congenital heart defects, and/or other physical abnormalities. Intellectual disability is also present. C Syndrome is thought to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “C Syndrome” as your search term in the Rare Disease Database.)Many other chromosomal disorders have features similar to Chromosome 13, Partial Monosomy 13q. The only way to determine which chromosomal disorder an individual has is through chromosomal testing. (For more information on these disorders, choose “Chromosome” as your search term in the Rare Disease Database.) | 241 | Chromosome 13, Partial Monosomy 13q |
nord_241_5 | Diagnosis of Chromosome 13, Partial Monosomy 13q | Diagnosis of Chromosome 13, Partial Monosomy 13q. | 241 | Chromosome 13, Partial Monosomy 13q |
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nord_241_6 | Therapies of Chromosome 13, Partial Monosomy 13q | In some cases, the diagnosis of Chromosome 13, Partial Monosomy 13q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may indicate a partial monosomy of chromosome 13q.The diagnosis of Chromosome 13, Partial Monosomy 13q may confirmed after birth (postnatally) based upon a thorough clinical evaluation, characteristic physical findings, chromosomal studies, and, in some cases, specialized enzyme testing (assay). According to the medical literature, if affected individuals exhibit intellectual impairment, growth delays, and/or retinoblastoma in association with craniofacial and/or digital abnormalities, a diagnosis of Chromosomal 13, Partial Monosomy 13q should be considered.In some cases, affected individuals with retinoblastoma may exhibit reduced activity of a certain enzyme (esterase D) due to deletions involving band q14 on chromosome 13. Researchers have determined that the genes for retinoblastoma and esterase D are very close together (proximal) on chromosome band 13q14 (i.e., the retinoblastoma gene maps to 13q14.1-q14.2, while the esterase D gene maps to 13q14.11). Therefore, both genes may be deleted in some individuals with Partial Monosomy 13q. As a result, an enzyme study (assay) that measures the levels of esterase D may be conducted as a screening test in individuals diagnosed with Chromosome 13, Partial Monosomy 13q to help predict the possible development of retinoblastoma. If such an assay reveals abnormally low levels of the esterase D enzyme, an affected individual should be carefully, regularly monitored for the possible development of the tumor.Retinoblastoma may be detected based upon characteristic clinical findings and specialized imaging tests. The most common presenting signs indicating retinoblastoma include the appearance of a whitish mass in the pupil area behind the lens of the eye (leukokoria or “cat's eye reflex”) and abnormal deviation of the eye (strabismus). Specialized imaging tests used to confirm retinoblastoma and/or characterize the tumor may include regular X-ray studies, the use of a special instrument to examine the interior of the eye (ophthalmoscopy), computer-assisted tomography (CT), magnetic resonance imaging (MRI), and/or ultrasonography. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the eye. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of the eye's tissue structure. In ultrasonography, reflected sound waves are used to create images. Additional specialized tests may also be conducted to further characterize the nature of the malignancy and to help determine potential, appropriate treatments.The diagnosis of certain congenital heart defects (e.g., Atrial or Ventricular Septal Defects) occurring in association with Chromosome 13, Partial Monosomy 13q may be confirmed by a thorough clinical examination and specialized tests that allow physicians to evaluate the structure and function of the heart. These tests may include X-ray studies, electrocardiogram (EKG), echocardiogram, and cardiac catheterization. X-ray studies may reveal abnormal enlargement of the heart (cardiomegaly) or malformation of other heart structures. An EKG, which records the heart's electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, ultrasonic waves are directed toward the heart, enabling physicians to study cardiac function and motion. During cardiac catheterization, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart, measure the pressure within the heart, and/or thoroughly identify anatomical abnormalities.Hirschsprung's Disease may be diagnosed by barium enema, a procedure in which a special contrast medium is infused into the rectum and X-rays are then taken of the area. Microscopic examination of a small tissue sample removed from the mucous membranes that line the rectum (biopsy) may confirm absence of nerve fibers (ganglia).Specialized imaging studies and/or additional tests may also be used to reveal other eye (ocular) abnormalities; certain genital, skeletal, kidney (renal), and/or brain malformations; and/or additional physical abnormalities potentially associated with Chromosome 13, Partial Monosomy 13q.The treatment of Chromosome 13, Partial Monosomy 13q is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, eye specialists, physicians who treat malignancies (oncologists), radiologists, cardiologists, neurologists, physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.In some cases, treatment may include surgical repair of certain malformations. For example, surgery may be performed to correct certain craniofacial, ocular, genital, skeletal, cardiac, and/or other malformations that may be associated with this disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.In affected children with retinoblastoma, the treatments used may depend upon whether one or both eyes are affected and/or the possibility of preserving and/or restoring vision. If one eye is affected (unilateral retinoblastoma), the eye may be surgically removed (enucleation) along with a portion of the optic nerve. Radiation and/or chemotherapy may then be conducted. If the tumor is very small, radiation alone may be used in some cases. If both eyes are involved (bilateral retinoblastoma), the more affected eye may be surgically removed while the other eye may be treated with antibiotics, radiation, chemotherapy, a procedure that uses extreme cold to destroy tissue (cryotherapy), and/or a procedure that uses intense, focused light (e.g., laser therapy) to heat and destroy tissue (photocoagulation). Corrective lenses and/or other measures may be used to help improve vision after treatment for retinoblastoma.In some cases, children with Partial Monosomy 13q may have visual problems resulting from additional eye abnormalities (e.g., colobomas, microphthalmia, cataracts). Corrective glasses, contact lenses, surgery, and/or other measures may also be used in such cases to help improve visual abnormalities.In affected children with craniosynostosis and trigonocephaly, surgery may be performed to correct the premature closure of the bones in the skull. In those with hydrocephalus, shunts may be implanted to drain excess cerebrospinal fluid away from the brain, relieving pressure.In many cases, Atrial or Ventricular Septal Defects may be corrected surgically. Before surgery, medical management may include treatment of symptoms related to congestive heart failure. Drugs such as digoxin may help to prevent irregular heartbeats and excessively rapid heartbeats (tachycardia). Restriction of salt in the diet, drugs that help to eliminate excessive fluid from the body (diuretics), and/or bed rest may also be effective therapies for congestive heart failure. In some cases, surgery may not be indicated for infants with small Ventricular Septal Defects that may close on their own or become less significant as the child matures and grows. Conservative treatment may include careful monitoring of symptoms and heart function.In addition, nutritional considerations may be important in infants with Atrial or Ventricular Septal Defects. Respiratory infections should be treated vigorously and early. Because of the risk of bacterial infection of the lining of the heart (endocarditis) and the heart valves, individuals with Atrial or Ventricular Septal Defects may be given antibiotic drugs before any surgical procedure, including dental procedures such as tooth extractions.In individuals with Partial Monosomy 13q who also exhibit Hirschsprung's Disease, the condition may often be corrected surgically during early childhood.Other treatment of Chromosome 13, Partial Monosomy 13q is symptomatic and supportive. A team approach may be helpful in ensuring that affected individuals reach their fullest potential. Such a team approach may include special remedial education, physical therapy, and other medical, social, or vocational services. Genetic counseling will be of benefit for families of children with Chromosome 13, Partial Monosomy 13q. Chromosomal studies are necessary to determine whether a chromosomal rearrangement is present in one of the parents. | Therapies of Chromosome 13, Partial Monosomy 13q. In some cases, the diagnosis of Chromosome 13, Partial Monosomy 13q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may indicate a partial monosomy of chromosome 13q.The diagnosis of Chromosome 13, Partial Monosomy 13q may confirmed after birth (postnatally) based upon a thorough clinical evaluation, characteristic physical findings, chromosomal studies, and, in some cases, specialized enzyme testing (assay). According to the medical literature, if affected individuals exhibit intellectual impairment, growth delays, and/or retinoblastoma in association with craniofacial and/or digital abnormalities, a diagnosis of Chromosomal 13, Partial Monosomy 13q should be considered.In some cases, affected individuals with retinoblastoma may exhibit reduced activity of a certain enzyme (esterase D) due to deletions involving band q14 on chromosome 13. Researchers have determined that the genes for retinoblastoma and esterase D are very close together (proximal) on chromosome band 13q14 (i.e., the retinoblastoma gene maps to 13q14.1-q14.2, while the esterase D gene maps to 13q14.11). Therefore, both genes may be deleted in some individuals with Partial Monosomy 13q. As a result, an enzyme study (assay) that measures the levels of esterase D may be conducted as a screening test in individuals diagnosed with Chromosome 13, Partial Monosomy 13q to help predict the possible development of retinoblastoma. If such an assay reveals abnormally low levels of the esterase D enzyme, an affected individual should be carefully, regularly monitored for the possible development of the tumor.Retinoblastoma may be detected based upon characteristic clinical findings and specialized imaging tests. The most common presenting signs indicating retinoblastoma include the appearance of a whitish mass in the pupil area behind the lens of the eye (leukokoria or “cat's eye reflex”) and abnormal deviation of the eye (strabismus). Specialized imaging tests used to confirm retinoblastoma and/or characterize the tumor may include regular X-ray studies, the use of a special instrument to examine the interior of the eye (ophthalmoscopy), computer-assisted tomography (CT), magnetic resonance imaging (MRI), and/or ultrasonography. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the eye. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of the eye's tissue structure. In ultrasonography, reflected sound waves are used to create images. Additional specialized tests may also be conducted to further characterize the nature of the malignancy and to help determine potential, appropriate treatments.The diagnosis of certain congenital heart defects (e.g., Atrial or Ventricular Septal Defects) occurring in association with Chromosome 13, Partial Monosomy 13q may be confirmed by a thorough clinical examination and specialized tests that allow physicians to evaluate the structure and function of the heart. These tests may include X-ray studies, electrocardiogram (EKG), echocardiogram, and cardiac catheterization. X-ray studies may reveal abnormal enlargement of the heart (cardiomegaly) or malformation of other heart structures. An EKG, which records the heart's electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, ultrasonic waves are directed toward the heart, enabling physicians to study cardiac function and motion. During cardiac catheterization, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart, measure the pressure within the heart, and/or thoroughly identify anatomical abnormalities.Hirschsprung's Disease may be diagnosed by barium enema, a procedure in which a special contrast medium is infused into the rectum and X-rays are then taken of the area. Microscopic examination of a small tissue sample removed from the mucous membranes that line the rectum (biopsy) may confirm absence of nerve fibers (ganglia).Specialized imaging studies and/or additional tests may also be used to reveal other eye (ocular) abnormalities; certain genital, skeletal, kidney (renal), and/or brain malformations; and/or additional physical abnormalities potentially associated with Chromosome 13, Partial Monosomy 13q.The treatment of Chromosome 13, Partial Monosomy 13q is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, eye specialists, physicians who treat malignancies (oncologists), radiologists, cardiologists, neurologists, physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.In some cases, treatment may include surgical repair of certain malformations. For example, surgery may be performed to correct certain craniofacial, ocular, genital, skeletal, cardiac, and/or other malformations that may be associated with this disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.In affected children with retinoblastoma, the treatments used may depend upon whether one or both eyes are affected and/or the possibility of preserving and/or restoring vision. If one eye is affected (unilateral retinoblastoma), the eye may be surgically removed (enucleation) along with a portion of the optic nerve. Radiation and/or chemotherapy may then be conducted. If the tumor is very small, radiation alone may be used in some cases. If both eyes are involved (bilateral retinoblastoma), the more affected eye may be surgically removed while the other eye may be treated with antibiotics, radiation, chemotherapy, a procedure that uses extreme cold to destroy tissue (cryotherapy), and/or a procedure that uses intense, focused light (e.g., laser therapy) to heat and destroy tissue (photocoagulation). Corrective lenses and/or other measures may be used to help improve vision after treatment for retinoblastoma.In some cases, children with Partial Monosomy 13q may have visual problems resulting from additional eye abnormalities (e.g., colobomas, microphthalmia, cataracts). Corrective glasses, contact lenses, surgery, and/or other measures may also be used in such cases to help improve visual abnormalities.In affected children with craniosynostosis and trigonocephaly, surgery may be performed to correct the premature closure of the bones in the skull. In those with hydrocephalus, shunts may be implanted to drain excess cerebrospinal fluid away from the brain, relieving pressure.In many cases, Atrial or Ventricular Septal Defects may be corrected surgically. Before surgery, medical management may include treatment of symptoms related to congestive heart failure. Drugs such as digoxin may help to prevent irregular heartbeats and excessively rapid heartbeats (tachycardia). Restriction of salt in the diet, drugs that help to eliminate excessive fluid from the body (diuretics), and/or bed rest may also be effective therapies for congestive heart failure. In some cases, surgery may not be indicated for infants with small Ventricular Septal Defects that may close on their own or become less significant as the child matures and grows. Conservative treatment may include careful monitoring of symptoms and heart function.In addition, nutritional considerations may be important in infants with Atrial or Ventricular Septal Defects. Respiratory infections should be treated vigorously and early. Because of the risk of bacterial infection of the lining of the heart (endocarditis) and the heart valves, individuals with Atrial or Ventricular Septal Defects may be given antibiotic drugs before any surgical procedure, including dental procedures such as tooth extractions.In individuals with Partial Monosomy 13q who also exhibit Hirschsprung's Disease, the condition may often be corrected surgically during early childhood.Other treatment of Chromosome 13, Partial Monosomy 13q is symptomatic and supportive. A team approach may be helpful in ensuring that affected individuals reach their fullest potential. Such a team approach may include special remedial education, physical therapy, and other medical, social, or vocational services. Genetic counseling will be of benefit for families of children with Chromosome 13, Partial Monosomy 13q. Chromosomal studies are necessary to determine whether a chromosomal rearrangement is present in one of the parents. | 241 | Chromosome 13, Partial Monosomy 13q |
nord_242_0 | Overview of Chromosome 14 Ring | Chromosome 14 Ring is a rare disorder that is characterized by abnormalities of the 14th chromosome. Affected infants and children typically have delays in the acquisition of skills that require the coordination of physical and mental activities (psychomotor delays), mental retardation, growth delays, and episodes of uncontrolled electrical activity in the brain (seizures). The disorder is also characterized by distinctive abnormalities of the head and facial (craniofacial) area. Such abnormalities may include an unusually small head (microcephaly) with a high forehead; an elongated face; widely spaced eyes (ocular hypertelorism); a thin upper lip; a flat nasal bridge with a prominent nasal tip; and large, low-set ears. | Overview of Chromosome 14 Ring. Chromosome 14 Ring is a rare disorder that is characterized by abnormalities of the 14th chromosome. Affected infants and children typically have delays in the acquisition of skills that require the coordination of physical and mental activities (psychomotor delays), mental retardation, growth delays, and episodes of uncontrolled electrical activity in the brain (seizures). The disorder is also characterized by distinctive abnormalities of the head and facial (craniofacial) area. Such abnormalities may include an unusually small head (microcephaly) with a high forehead; an elongated face; widely spaced eyes (ocular hypertelorism); a thin upper lip; a flat nasal bridge with a prominent nasal tip; and large, low-set ears. | 242 | Chromosome 14 Ring |
nord_242_1 | Symptoms of Chromosome 14 Ring | The symptoms and findings associated with Chromosome 14 Ring may vary in range and severity from case to case. However, in many individuals with the disorder, such abnormalities may include growth delays before and after birth (prenatal and postnatal growth retardation), diminished muscle tone (hypotonia), feeding difficulties during infancy, psychomotor delays, and mental retardation. In addition, recurrent seizures (epilepsy) typically develop beginning during infancy or early childhood. The specific form a seizure takes and its associated symptoms may vary, depending upon the region(s) of the brain affected and other factors. For example, seizure episodes may be characterized by shock-like contractions of certain muscles or muscle groups (myoclonic seizures); increased stiffness (rigidity) and rapid, rhythmic contraction and relaxation of certain muscle groups (tonic-clonic seizures); sensory or behavioral disturbances; lost consciousness; and/or impaired control of certain voluntary functions, such as bowel or bladder control. (For more information, please choose “epilepsy” as your search term in the Rare Disease Database.)Individuals with Chromosome 14 Ring may also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. These abnormalities may include a small head (microcephaly) with a high forehead; an elongated face; and a flat nasal bridge with a prominent nasal tip and slightly upturned nostrils (anteverted nares). The eyes may be widely spaced (ocular hypertelorism) with downwardly slanting eyelid folds (palpebral fissures) and vertical skin folds covering the eyes' inner corners (epicanthic folds). Affected individuals may also have additional characteristic features, such as a thin upper lip; downwardly turned corners of the mouth; a highly arched roof of the mouth (palate); an unusually small jaw (micrognathia); and large, low-set ears.Chromosome 14 Ring may also be characterized by other physical abnormalities, including a short neck with excessive skin folds; abnormal skin ridge patterns (dermatoglyphics), such as the presence of a single crease across the palm (simian crease); widely spaced nipples; and abnormalities of skin coloration (pigmentation). These may include vitiligo, a chronic condition in which patches of skin lose pigmentation, or the presence of cafe-au-lait spots, which are light brown or pale tan discolorations of the skin. (For more information, please choose “vitiligo” as your search term in the Rare Disease Database.) Some affected individuals may also have abnormalities of the nerve-rich membrane that forms the innermost region of the eye (retina), such as abnormalities of retinal pigmentation.In some cases, certain additional abnormalities may also be associated with Chromosome 14 Ring. For example, in addition to seizures, other neurological symptoms may sometimes be present, such as an impaired ability to coordinate voluntary movements (ataxia) or rhythmic involuntary movements of a part or parts of the body (tremor) that occur or may increase with certain goal-directed voluntary actions (intention tremor). In addition, in some affected individuals, certain joints may become permanently flexed or extended in fixed postures (joint contractures). Abnormalities of the heart may also be present at birth (congenital heart defects), such as narrowing (stenosis) of the major artery that carries oxygenated blood to the body (aorta) or the artery that transports oxygen-depleted blood to the lungs (pulmonary artery). Individuals with Chromosome 14 Ring may also be susceptible to repeated respiratory infections. | Symptoms of Chromosome 14 Ring. The symptoms and findings associated with Chromosome 14 Ring may vary in range and severity from case to case. However, in many individuals with the disorder, such abnormalities may include growth delays before and after birth (prenatal and postnatal growth retardation), diminished muscle tone (hypotonia), feeding difficulties during infancy, psychomotor delays, and mental retardation. In addition, recurrent seizures (epilepsy) typically develop beginning during infancy or early childhood. The specific form a seizure takes and its associated symptoms may vary, depending upon the region(s) of the brain affected and other factors. For example, seizure episodes may be characterized by shock-like contractions of certain muscles or muscle groups (myoclonic seizures); increased stiffness (rigidity) and rapid, rhythmic contraction and relaxation of certain muscle groups (tonic-clonic seizures); sensory or behavioral disturbances; lost consciousness; and/or impaired control of certain voluntary functions, such as bowel or bladder control. (For more information, please choose “epilepsy” as your search term in the Rare Disease Database.)Individuals with Chromosome 14 Ring may also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. These abnormalities may include a small head (microcephaly) with a high forehead; an elongated face; and a flat nasal bridge with a prominent nasal tip and slightly upturned nostrils (anteverted nares). The eyes may be widely spaced (ocular hypertelorism) with downwardly slanting eyelid folds (palpebral fissures) and vertical skin folds covering the eyes' inner corners (epicanthic folds). Affected individuals may also have additional characteristic features, such as a thin upper lip; downwardly turned corners of the mouth; a highly arched roof of the mouth (palate); an unusually small jaw (micrognathia); and large, low-set ears.Chromosome 14 Ring may also be characterized by other physical abnormalities, including a short neck with excessive skin folds; abnormal skin ridge patterns (dermatoglyphics), such as the presence of a single crease across the palm (simian crease); widely spaced nipples; and abnormalities of skin coloration (pigmentation). These may include vitiligo, a chronic condition in which patches of skin lose pigmentation, or the presence of cafe-au-lait spots, which are light brown or pale tan discolorations of the skin. (For more information, please choose “vitiligo” as your search term in the Rare Disease Database.) Some affected individuals may also have abnormalities of the nerve-rich membrane that forms the innermost region of the eye (retina), such as abnormalities of retinal pigmentation.In some cases, certain additional abnormalities may also be associated with Chromosome 14 Ring. For example, in addition to seizures, other neurological symptoms may sometimes be present, such as an impaired ability to coordinate voluntary movements (ataxia) or rhythmic involuntary movements of a part or parts of the body (tremor) that occur or may increase with certain goal-directed voluntary actions (intention tremor). In addition, in some affected individuals, certain joints may become permanently flexed or extended in fixed postures (joint contractures). Abnormalities of the heart may also be present at birth (congenital heart defects), such as narrowing (stenosis) of the major artery that carries oxygenated blood to the body (aorta) or the artery that transports oxygen-depleted blood to the lungs (pulmonary artery). Individuals with Chromosome 14 Ring may also be susceptible to repeated respiratory infections. | 242 | Chromosome 14 Ring |
nord_242_2 | Causes of Chromosome 14 Ring | Chromosome 14 Ring results from loss (deletion) of genetic material from both ends of the 14th chromosome and joining of the ends to form a ring. Associated symptoms and findings may vary, depending upon the amount of genetic material lost from the 14th chromosome or the stability of the ring chromosome during subsequent cellular divisions (i.e., mitosis). Evidence suggests that features associated with Chromosome 14 Ring may result from relatively small deletions of genetic material from the long arm (q) of chromosome 14 (14q).Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.Chromosome 14 Ring usually appears to be caused by spontaneous or “de novo” errors early during the development of the embryo. The parents of an affected child typically have normal chromosomes, and the probability of having another child with the chromosomal abnormality is low. However, when a parent of the affected individual has Chromosome 14 Ring, the chances are greater of having another child with this chromosomal abnormality. | Causes of Chromosome 14 Ring. Chromosome 14 Ring results from loss (deletion) of genetic material from both ends of the 14th chromosome and joining of the ends to form a ring. Associated symptoms and findings may vary, depending upon the amount of genetic material lost from the 14th chromosome or the stability of the ring chromosome during subsequent cellular divisions (i.e., mitosis). Evidence suggests that features associated with Chromosome 14 Ring may result from relatively small deletions of genetic material from the long arm (q) of chromosome 14 (14q).Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.Chromosome 14 Ring usually appears to be caused by spontaneous or “de novo” errors early during the development of the embryo. The parents of an affected child typically have normal chromosomes, and the probability of having another child with the chromosomal abnormality is low. However, when a parent of the affected individual has Chromosome 14 Ring, the chances are greater of having another child with this chromosomal abnormality. | 242 | Chromosome 14 Ring |
nord_242_3 | Affects of Chromosome 14 Ring | Chromosome 14 Ring is an extremely rare chromosomal disorder that has appeared to affect males slightly more often than females. There have been over 40 cases reported in the medical literature. | Affects of Chromosome 14 Ring. Chromosome 14 Ring is an extremely rare chromosomal disorder that has appeared to affect males slightly more often than females. There have been over 40 cases reported in the medical literature. | 242 | Chromosome 14 Ring |
nord_242_4 | Related disorders of Chromosome 14 Ring | Additional chromosomal disorders may have features similar to those associated with Chromosome 14 Ring. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database.) | Related disorders of Chromosome 14 Ring. Additional chromosomal disorders may have features similar to those associated with Chromosome 14 Ring. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use “chromosome” as your search term in the Rare Disease Database.) | 242 | Chromosome 14 Ring |
nord_242_5 | Diagnosis of Chromosome 14 Ring | In some cases, a diagnosis of Chromosome 14 Ring may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on such fluid or tissue samples may reveal the presence of Chromosome 14 Ring.The diagnosis of Chromosome 14 Ring may be confirmed after birth (postnatally) based upon a thorough clinical evaluation, characteristic physical findings, and chromosomal analysis. Specialized testing may also be conducted to detect certain findings that may be associated with the disorder. Such testing may include electroencephalography (EEG) and computerized tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain. An EEG is a noninvasive diagnostic technique that records the brain's electrical activity. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves form detailed cross-sectional images of the brain. | Diagnosis of Chromosome 14 Ring. In some cases, a diagnosis of Chromosome 14 Ring may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on such fluid or tissue samples may reveal the presence of Chromosome 14 Ring.The diagnosis of Chromosome 14 Ring may be confirmed after birth (postnatally) based upon a thorough clinical evaluation, characteristic physical findings, and chromosomal analysis. Specialized testing may also be conducted to detect certain findings that may be associated with the disorder. Such testing may include electroencephalography (EEG) and computerized tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain. An EEG is a noninvasive diagnostic technique that records the brain's electrical activity. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves form detailed cross-sectional images of the brain. | 242 | Chromosome 14 Ring |
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