Post by Master Kim on Apr 14, 2015 19:14:07 GMT -5
Marfan syndrome - en.wikipedia.org/wiki/Marfan_syndrome
Marfan syndrome (also called Marfan's syndrome) is a genetic disorder of connective tissue. It has a variable clinical presentation, ranging from mild to severe systemic disease. The most serious manifestations involve defects of the heart valves and aorta, which may lead to early death if not properly managed. The syndrome also may affect the lungs, eyes, dural sac surrounding the spinal cord, the skeleton, and the hard palate. People with Marfan syndrome tend to be unusually tall, with long limbs and long, thin fingers and toes.
The syndrome is caused by the misfolding of fibrillin-1, a glycoprotein which forms elastic fibers in connective tissue and contributes to cell signaling activity by binding to and sequestering transforming growth factor beta (TGF-β). The mutated fibrillin binds poorly to TGF-β, which results in an accumulation of excess TGF-β in the lungs, heart valves, and aorta. This in turn causes abnormal structure and function of vascular smooth muscle and reduced integrity of the extracellular matrix, which weaken the tissues and cause the features of Marfan syndrome.
Named after Antoine Marfan, the French pediatrician who first described the condition in 1896, the disease is an autosomal dominant disorder. Management often includes the use of angiotensin II receptor antagonists (ARBs) and beta blockers.
Micrograph of myxomatous degeneration of the aortic valve. Surgical specimen. Movat's stain (Black = nuclei, elastic fibres. Yellow = collagen, reticular fibers. Blue = ground substance, mucin. Bright red = Fibrin. Red = muscle.) In myxomatous degeneration, the ventricularis layer (composed primarily of elastic tissue) is thinned and the spongiosa layer (composed of loose connective tissue) is thickened. On the image, the fibrosa layer (composed of collagen) is on the top, the thickened spongiosa layer below it and the ventricularis layer (made of elastic tissue) at the bottom. The ventricularis layer, as the name may suggest, is closest to the (left) ventricle. The fibrosa layer is closest to the sinus of valsalva. See also Marfan's syndrome - a condition, due to a defect in fibrillin (an essential component of elastic fibers), in which myxomatous degeneration is common.
Lens dislocation in Marfan syndrome with the lens being kidney-shaped and resting against the ciliary body
Thumb sign; upper: normal, lower: Marfan syndrome
Signs and symptoms
More than 30 different signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal system and are found in numerous other diseases (see Differential diagnosis, below). Therefore, distinguishing Marfan syndrome from other "marfanoid" syndromes requires the assessment of non-skeletal clinical and laboratory findings—especially of the eyes, aorta, and heart. Complicating the physical assessment of such persons, considerable clinical variability occurs within families carrying an identical DNA variant.
Skeletal system
Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height. Some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes. Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal curvature of the spine, abnormal indentation or protrusion of the sternum, abnormal joint flexibility, a high palate, malocclusions, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets.
Eyes
Lens dislocation in Marfan syndrome with the lens being kidney-shaped and resting against the ciliary body
In Marfan syndrome the health of the eye can be affected in many ways but the principal change is partial lens dislocation (the lens is shifted out of its normal position). This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. (The lens can be seen as a trampoline surface supported by the zonules as springs). Fibrillin 1 (FBN1) is a component of the zonules and mutations in FBN1 are found in most individuals diagnosed with Marfan syndrome. Those mutations weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards but it can shift in other directions as well. Nearsightedness and blurred vision are common, but farsightedness can also result particularly if the lens is highly subluxed. Subluxation (partial dislocation) of the lens can be detected clinically in 80% of patients by the use of a slit-lamp biomicroscope. If the lens subluxation is subtle then imaging with high resolution ultrasound biomicroscopy might be used. Other problems are a greater risk of retinal detachment, an earlier onset of cataract formation and a higher risk of chronic open angle glaucoma. Rarely, the lens can dislocate through the pupillary opening to precipitate an ocular emergency, pupillary block glaucoma. The latter is rare but in the context of direct ocular trauma in a patient with Marfan syndrome it should be ruled out.
Cardiovascular system
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system: undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or chest pain radiating to the back, shoulder, or arm. Cold arms, hands and feet can also be linked to Marfan syndrome because of inadequate circulation. A heart murmur, abnormal reading on an EKG, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse of the mitral or aortic valves (which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with Marfan syndrome (see mitral valve prolapse, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta causes an aortic aneurysm or aortic dissection, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.
Because underlying connective tissue abnormalities cause Marfan syndrome, there is an increased incidence of dehiscence of prosthetic mitral valve. Care should be taken to attempt repair of damaged heart valves rather than replacement.
During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.
Lungs
Pulmonary symptoms are not a major feature of Marfan syndrome, but spontaneous pneumothorax is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, it can cause death. Other possible pulmonary manifestations of Marfan syndrome include sleep apnea and idiopathic obstructive lung disease.[medical citation needed] Pathologic changes in the lungs have been described such as cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as middle lobe hypoplasia.
Central nervous system
Dural ectasia, the weakening of the connective tissue of the dural sac encasing the spinal cord, can result in a loss of quality of life. It can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain, leg pain, abdominal pain, other neurological symptoms in the lower extremities, or headaches – symptoms which usually diminish when lying flat. On X-ray however dural ectasia is not often visible in the early stages. A worsening of symptoms might warrant an MRI of the lower spine. Dural ectasia that has progressed to this stage would appear in an MRI as a dilated pouch wearing away at the lumbar vertebrae. Other spinal issues associated with Marfan syndrome include degenerative disc disease, spinal cysts and dysfunction of the autonomic nervous system.
Marfan syndrome (also called Marfan's syndrome) is a genetic disorder of connective tissue. It has a variable clinical presentation, ranging from mild to severe systemic disease. The most serious manifestations involve defects of the heart valves and aorta, which may lead to early death if not properly managed. The syndrome also may affect the lungs, eyes, dural sac surrounding the spinal cord, the skeleton, and the hard palate. People with Marfan syndrome tend to be unusually tall, with long limbs and long, thin fingers and toes.
The syndrome is caused by the misfolding of fibrillin-1, a glycoprotein which forms elastic fibers in connective tissue and contributes to cell signaling activity by binding to and sequestering transforming growth factor beta (TGF-β). The mutated fibrillin binds poorly to TGF-β, which results in an accumulation of excess TGF-β in the lungs, heart valves, and aorta. This in turn causes abnormal structure and function of vascular smooth muscle and reduced integrity of the extracellular matrix, which weaken the tissues and cause the features of Marfan syndrome.
Named after Antoine Marfan, the French pediatrician who first described the condition in 1896, the disease is an autosomal dominant disorder. Management often includes the use of angiotensin II receptor antagonists (ARBs) and beta blockers.
Micrograph of myxomatous degeneration of the aortic valve. Surgical specimen. Movat's stain (Black = nuclei, elastic fibres. Yellow = collagen, reticular fibers. Blue = ground substance, mucin. Bright red = Fibrin. Red = muscle.) In myxomatous degeneration, the ventricularis layer (composed primarily of elastic tissue) is thinned and the spongiosa layer (composed of loose connective tissue) is thickened. On the image, the fibrosa layer (composed of collagen) is on the top, the thickened spongiosa layer below it and the ventricularis layer (made of elastic tissue) at the bottom. The ventricularis layer, as the name may suggest, is closest to the (left) ventricle. The fibrosa layer is closest to the sinus of valsalva. See also Marfan's syndrome - a condition, due to a defect in fibrillin (an essential component of elastic fibers), in which myxomatous degeneration is common.
Lens dislocation in Marfan syndrome with the lens being kidney-shaped and resting against the ciliary body
Thumb sign; upper: normal, lower: Marfan syndrome
Signs and symptoms
More than 30 different signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal system and are found in numerous other diseases (see Differential diagnosis, below). Therefore, distinguishing Marfan syndrome from other "marfanoid" syndromes requires the assessment of non-skeletal clinical and laboratory findings—especially of the eyes, aorta, and heart. Complicating the physical assessment of such persons, considerable clinical variability occurs within families carrying an identical DNA variant.
Skeletal system
Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height. Some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes. Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal curvature of the spine, abnormal indentation or protrusion of the sternum, abnormal joint flexibility, a high palate, malocclusions, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets.
Eyes
Lens dislocation in Marfan syndrome with the lens being kidney-shaped and resting against the ciliary body
In Marfan syndrome the health of the eye can be affected in many ways but the principal change is partial lens dislocation (the lens is shifted out of its normal position). This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. (The lens can be seen as a trampoline surface supported by the zonules as springs). Fibrillin 1 (FBN1) is a component of the zonules and mutations in FBN1 are found in most individuals diagnosed with Marfan syndrome. Those mutations weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards but it can shift in other directions as well. Nearsightedness and blurred vision are common, but farsightedness can also result particularly if the lens is highly subluxed. Subluxation (partial dislocation) of the lens can be detected clinically in 80% of patients by the use of a slit-lamp biomicroscope. If the lens subluxation is subtle then imaging with high resolution ultrasound biomicroscopy might be used. Other problems are a greater risk of retinal detachment, an earlier onset of cataract formation and a higher risk of chronic open angle glaucoma. Rarely, the lens can dislocate through the pupillary opening to precipitate an ocular emergency, pupillary block glaucoma. The latter is rare but in the context of direct ocular trauma in a patient with Marfan syndrome it should be ruled out.
Cardiovascular system
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system: undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or chest pain radiating to the back, shoulder, or arm. Cold arms, hands and feet can also be linked to Marfan syndrome because of inadequate circulation. A heart murmur, abnormal reading on an EKG, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse of the mitral or aortic valves (which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with Marfan syndrome (see mitral valve prolapse, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta causes an aortic aneurysm or aortic dissection, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.
Because underlying connective tissue abnormalities cause Marfan syndrome, there is an increased incidence of dehiscence of prosthetic mitral valve. Care should be taken to attempt repair of damaged heart valves rather than replacement.
During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.
Lungs
Pulmonary symptoms are not a major feature of Marfan syndrome, but spontaneous pneumothorax is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, it can cause death. Other possible pulmonary manifestations of Marfan syndrome include sleep apnea and idiopathic obstructive lung disease.[medical citation needed] Pathologic changes in the lungs have been described such as cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as middle lobe hypoplasia.
Central nervous system
Dural ectasia, the weakening of the connective tissue of the dural sac encasing the spinal cord, can result in a loss of quality of life. It can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain, leg pain, abdominal pain, other neurological symptoms in the lower extremities, or headaches – symptoms which usually diminish when lying flat. On X-ray however dural ectasia is not often visible in the early stages. A worsening of symptoms might warrant an MRI of the lower spine. Dural ectasia that has progressed to this stage would appear in an MRI as a dilated pouch wearing away at the lumbar vertebrae. Other spinal issues associated with Marfan syndrome include degenerative disc disease, spinal cysts and dysfunction of the autonomic nervous system.
Based on Ascetic Saahm's formula #1, fostering large intestine, subdue LU10, ST41, SP2, HT8, BL60, KI2, GB38 and LR2.